Insaf Qureshi | University of Hyderabad (original) (raw)

Papers by Insaf Qureshi

Nutrition and Cancer, 2016

Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of med... more Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of medicine. Therefore, the present study was designed to evaluate the effects of A. nilagirica extracts/fractions on inhibition of proliferation and apoptosis in a human monocytic leukemia (THP-1) cell line. The crude extracts (A. nilagirica ethyl acetate extract [ANE] and A. nilagirica methanolic extract [ANA]) showed cytotoxic activity toward THP-1 cells with the IC 50 values of 38.21 § 7.37 and 132.41 § 7.19 mg/ml, respectively. However, the cytotoxic activity of active fractions (ANE-B and ANM-9) obtained after column chromatography was found to be much more pronounced than their parent extracts. The IC 50 values of ANE-B and ANM-9 were found to be 27.04 § 2.54 mg/ml and 12.70 § 4.79 mg/ml, respectively, suggesting greater susceptibility of the malignant cells. Cell cycle analysis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) assay revealed that inhibition of cell growth by A. nilagirica fractions on THP-1 cells was mediated by apoptosis. Active fractions of A. nilagirica increased the expression levels of caspase-3, ¡7, and poly-ADP-ribose polymerase (PARP), a critical member of the apoptotic pathway. These results suggested that active fractions of A. nilagirica may play a promising role in growth suppression by inducing apoptosis in human monocytic leukemic cells via mitochondria-dependent and death receptordependent apoptotic pathways.

PLOS ONE, 2015

Nucleotide sequence polymorphisms among R gene alleles influence the process of coevolutionary in... more Nucleotide sequence polymorphisms among R gene alleles influence the process of coevolutionary interaction between host and pathogen by shaping the response of host plants towards invading pathogens. Here, we present the DNA sequence polymorphisms and diversities present among natural alleles of three rice bacterial blight resistance genes, Xa21, Xa26 and xa5. The diversity was examined across different wild relatives and cultivars of Oryza species. Functional significance of selected alleles was evaluated through semiquantitative reverse transcription polymerase chain reaction and real time PCR. The greatest nucleotide diversity and singleton variable sites (SVS) were present in Xa26 (π = 0.01958; SVS = 182) followed by xa5 and Xa21 alleles. The highest frequency of single nucleotide polymorphisms were observed in Xa21 alleles and least in xa5. Transition bias was observed in all the genes and 'G' to 'A' transitions were more favored than other form of transitions. Neutrality tests failed to show the presence of selection at these loci, though negative Tajima's D values indicate the presence of a rare form of polymorphisms. At the interspecies level, O. nivara exhibited more diversity than O. sativa. We have also identified two nearly identical resistant alleles of xa5 and two sequentially identical alleles of Xa21. The alleles of xa5 showed basal levels of expression while Xa21 alleles were functionally not expressed.

Malaria Journal, 2010

INVITED SPEAKER PRESENTATIONS I1 Development of an attenuated sporozoite vaccine to prevent and e... more INVITED SPEAKER PRESENTATIONS I1 Development of an attenuated sporozoite vaccine to prevent and eliminate Plasmodium falciparum malaria Peter F Billingsley ORAL PRESENTATIONS O1 Studies on the breeding swarms of Anopheles gambiae complex in malaria control perspective Benoît S Assogba O2 Variant surface antigens in cerebral malaria: distinct from others and similar to each other? Agnès Aubouy O3 Identification and characterization of novel Plasmodium falciparum cyclophilins and their roles in the antimalarial actions of cyclosporin A and derivatives Angus Bell O4 Development of a novel drug for uncomplicated malaria targeting the mitochondrial NADH:quinone oxidoreductase Giancarlo A Biagini O5 Larval time-to-hatch and insecticide resistance in the major malaria vector Anopheles gambiae from Ghana Basil D Brooke O6 Progress in the development of Reversed Chloroquine molecules as antimalarial therapy Steven J Burgess O7 Modeling the effects of vector control interventions in reducing malaria transmission, morbidity and mortality Konstantina Boutsika O8 A library of functional recombinant Plasmodium falciparum merozoite surface proteins Cecile Crosnier O9 Antimalarial activity of ulein and proof of its action on the Plasmodium falciparum digestive vacuole Alaíde Braga de Oliveira O10 A micro-bead device to explore Plasmodium falciparum-infected, spherocytic or aged red blood cells prone to mechanical retention by spleen endothelial slits Innocent Safeukui O11 Predicted impact of mosquito-stage transmission-blocking vaccines using an ensemble of microsimulations Aurelio Di Pasquale O12 Controlling malaria in Niger with bednets: how to take the Big Picture Duchemin Jean-Bernard O13 Adaptation of in vitro cytoadherence assay to Plasmodium knowlesi field isolates Farrah A Fatih O14 Molecular epidemiology of force of infection in malaria Ingrid Felger O15 Characterization and comparative sequence analyzes of GABA receptor gene in Asian main malaria mosquito, Anopheles stephensi Navid Dinparast Djadid O16 Refreshed approaches to the therapy of malaria-the case of natural medicine Hagai Ginsburg O17 Impact of protective haemoglobins C and S on P. falciparum malaria transmission in endemic area Louis C Gouagna O18 Household size explains successful malaria eradication Lena Hulden O19 Complete abrogation of sporozoite-induced sterile immunity by blood stage parasites of homologous and heterologous malaria species Megumi Inoue O20 A comprehensive survey of protein palmitoylation in late blood-stage Plasmodium falciparum Julian C Rayner O21 Wild chimpanzees are infected with homologous types of human malaria Marco Kaiser O22 Viral vectored transmission blocking vaccines against Plasmodium falciparum Melissa C Kapulu O23 What has been the contribution of the first Global Fund grant (2003-2006) to malaria control and health system strengthening in Timor-Leste? Joao Martins O24 Polyamine uptake in the malaria parasite, Plasmodium falciparum, is dependent on the parasite's membrane potential AI Louw O25 Stepwise dissection of Plasmodium falciparum merozoite invasion of the human erythrocyte Jake Baum O26 Identification of genetic markers of resistance to Artemisinin Combination Therapy in the rodent model Plasmodium chabaudi Louise A Rodrigues O27 The role of LCCL proteins in malaria transmission Sadia Saeed O28 Transfer of 4-hydroxynonenal, a inhibitory hemozoin (HZ) product, from HZ or HZ-laden phagocytes to developing human erythroid cells. A model for erythropoiesis inhibition in malaria anemia Paolo Arese O29 Sugar-fermenting yeast as an organic source of carbon dioxide to attract the malaria mosquito Anopheles gambiae s.s. Renate C Smallegange O30 Ancient out-of-Africa migration of Plasmodium falciparum along with modern humans Kazuyuki Tanabe O31 Intra-host dynamics of mixed species malaria parasite infections in mice and mosquitoes Richard Culleton O32 Investigating transcriptional regulation of Plasmodium falciparum upon drug perturbation Tharina van Brummlen POSTER PRESENTATIONS P1 Initial surveillance of suspected undesirable drug reactions to some Artemisinin-based combination therapies (ACTs) in Lagos, Nigeria Bamgboye M Afolabi, Antonia Dunkwu, A C Oparah P2 Plasmodium falciparum, vivax and malariae detection during the low transmission season in the hill tracts of Bangladesh

PLoS biology, Jan 5, 2018

Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resist... more Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice. HF inhibits IL-1β through general control nonderepressible 2 kinase (GCN2)-dependent activation of the cytoprotective integrated stress response (ISR) pathway, resulting in rerouting of IL-1β mRNA from translationally active polysomes to inactive ribocluster complexes-such as stress granules (SGs)-via recruitment of RNA-binding proteins (RBPs) T cell-restricted intracellular antigen-1(TIA-1)/TIA-1-related (TIAR), which are further cleared through induction of autophagy. GCN2 ablation resulted in reduced autophagy and SG formation, which is inversely correlated with IL-1β prod...

Scientific reports, Jan 20, 2016

Tuberculosis caused by Mycobacterium tuberculosis is a global encumbrance and it is estimated tha... more Tuberculosis caused by Mycobacterium tuberculosis is a global encumbrance and it is estimated that nearly one third population of the world acts as a reservoir for this pathogen without any symptoms. In this study, we attempted to characterise one of the genes of DosR regulon, Rv3131, a FMN binding nitroreductase domain containing protein, for its ability to alter cytokine profile, an essential feature of M. tuberculosis latency. Recombinant Rv3131 stimulated pro-inflammatory cytokines in THP-1 cells and human peripheral blood mononuclear cells in a time and dose dependent manner. In silico analyses using docking and simulations indicated that Rv3131 could strongly interact with TLR2 via a non-covalent bonding which was further confirmed using cell based colorimetric assay. In THP-1 cells treated with Rv3131 protein, a significant upsurge in the surface expression, overall induction and expression of mRNA of TLR2 was observed when analysed by flow cytometry, western blotting and rea...

Free Radicals and Antioxidants, 2018

Background: Artemisia absinthium is a valuable medicinal plant which has vast ethnopharmacologica... more Background: Artemisia absinthium is a valuable medicinal plant which has vast ethnopharmacological significance. Traditionally, it has been used to cure various ailments like fever, jaundice and other gastrointestinal problems in humans of ancient periods. Objective: The aim of the present study was to evaluate antioxidant and anti-proliferative properties of this medicinal plant. Methods: Total phenolics as well as flavonoid content in different extracts were estimated. Antioxidant activity was evaluated by metal (copper and iron) chelating ability and scavenging of free radicals (DPPH, ABTS, Nitric oxide, Hydroxyl, etc.). 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) assay was done for evaluation of the antiproliferative ability of the extracts. The Fourier Transform Infrared (FTIR) analysis was performed to identify the functional groups present in the metabolites in the different extracts. Results: Among all the extracts, Phenolic and flavonoid content was...

Mycobacterium tuberculosis, the cause of tuberculosis in humans, is present approximately in one ... more Mycobacterium tuberculosis, the cause of tuberculosis in humans, is present approximately in one third of the world's population, mostly in a dormant state. The proteins encoded by the dormancy survival regulon (DosR regulon) are mainly responsible for survival of the bacilli in a latent form. To maintain latency, mycobacteria orchestrate a balanced interplay of different cytokines secreted by immune cells during the granulomatous stage. The function of most of the DosR regulon proteins of M. tuberculosis is unknown. In this study, we have shown that one of the DosR regulon proteins, DATIN, encoded by the gene Rv0079, can stimulate macrophages and peripheral blood mononuclear cells (PBMC) to secrete important cytokines that may be significant in granuloma formation and its maintenance. The expression level of DATIN in Mycobacterium bovis BCG was found to be upregulated in pH stress and microaerobic conditions. Computational modeling, docking and simulation study suggested that DATIN might interact with TLR2. This was further confirmed through the interaction of recombinant DATIN with TLR2 expressed by HEK293 cells. When in vitro differentiated THP-1 cells were treated with recombinant DATIN, increased secretion of TNF-α, IL-1β and IL-8 was observed in a dose dependent manner. When differentiated THP-1 cells were infected with a modified BCG strain that overexpressed DATIN, augmented secretions of TNF-α, IL-1β and IL-8 were observed as compared to a reference BCG strain containing empty vector. Similarly, human PBMCs when infected with M. bovis BCG that overexpressed DATIN, upregulated secretion of proinflammatory cytokines IFN-γ, TNF-α, IL-1β and IL-8. The cytokine profiles dissected herein point to a possible role of DATIN in maintenance of latency with the help of the proinflammatory responses.

Mir Zahoor Gul, Sambamurthy Chandrasekaran*, Mohd Yasin Bhat, Radheshyam Maurya*, Insaf Ahmed Qur... more Mir Zahoor Gul, Sambamurthy Chandrasekaran*, Mohd Yasin Bhat, Radheshyam Maurya*, Insaf Ahmed Qureshi** and Irfan Ahmad Ghazi Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500 046, Telangana State, India *Department of Animal Biology, School of Life Sciences, University of Hyderabad,Gachibowli, Hyderabad 500 046, Telangana State, India **Department of Biotechnology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500 046, Telangana State, India

Novel coronavirus disease 2019 (COVID-19) emerges as a serious threat to public health globally. ... more Novel coronavirus disease 2019 (COVID-19) emerges as a serious threat to public health globally. The rapid spreading of COVID-19, caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), proclaimed the multitude of applied research needed not only to save the human health but also for the environmental safety. As per the recent World Health Organization reports, the novel corona virus may never be wiped out completely from the world. In this connection, the inhibitors already designed against different targets of previous human coronavirus (HCoV) infections will be a great starting point for further optimization. Pinpointing biochemical events censorious to the HCoV lifecycle has provided two proteases: a papain-like protease (PLpro) and a 3C-like protease (3CLpro) enzyme essential for viral replication. In this study, naphthyl derivatives inhibiting PLpro enzyme were subjected to robust molecular modelling approaches to understand different structural fingerpr...

showed four-bladed b-propeller structure having a pseudo 4-fold molecular symmetry along a metal ... more showed four-bladed b-propeller structure having a pseudo 4-fold molecular symmetry along a metal ion-binding central channel. The structure represents typical mammalian hemopexin fold with discernible features correlated with the possible functional variations. The protein was found to exist in the dimeric state. While LS-24 dimer binds to spermine in the crystal structure as well as in solution, binding of heme in solution resulted in the dissociation of the dimer into monomers with concomitant release of bound spermine. Interactions of heme and spermine with LS-24 bear physiological implications. While binding of spermine to LS-24 can be linked with polyamine biosynthesis that of heme correlates with oxidative stress. Mutually exclusive binding of heme and spermine in different oligomeric states suggest a role for LS-24 in sensing oxidative stress

Archives of Biochemistry and Biophysics

ACS Omega

A leucine aminopeptidase primarily hydrolyzes amino acid leucine from the N-terminus end of prote... more A leucine aminopeptidase primarily hydrolyzes amino acid leucine from the N-terminus end of proteins and is involved in free amino acid regulation, which makes it a potential therapeutic target against neglected tropical diseases including leishmaniasis. We here report the purification and characterization of the leucine aminopeptidase from Leishmania donovani (LdLAP). Using a set of biophysical and biochemical methods, we demonstrate that this enzyme was properly folded after expression in a bacterial system and catalytically active when supplemented with divalent metal cofactors with synthetic fluorogenic peptides. Subsequently, enzymatic inhibition assay denoted that LdLAP activity was inhibited by peptidomimetics, particularly actinonin, which caused potent inhibition and exhibited stronger binding association with the LdLAP. Stronger association of actinonin with the LdLAP was due to a stable complex formation mostly mediated by hydrogen bonding with catalytic and substrate-binding residues in the C-terminal catalytic domain. With molecular dynamics simulation studies, we demonstrate that peptidomimetics retain their topological space in the LdLAP catalytic pocket and form a stable complex. These results expand the current knowledge of aminopeptidase biochemistry and highlight that specific actinonin or peptidomimetic-based inhibitors may emerge as leads to combat leishmaniasis.

Journal of Biomolecular Structure and Dynamics

COVID-19, caused by SARS-CoV-2, is severe respiratory illnesses leading to millions of deaths wor... more COVID-19, caused by SARS-CoV-2, is severe respiratory illnesses leading to millions of deaths worldwide in very short span. The high case fatality rate and the lack of medical counter measures emphasize for an urgent quest to develop safe and effective vaccine. Receptor-binding domain (RBD) of spike protein of SARS-CoV-2 binds to the ACE2 receptor on human host cell for the viral attachment and entry, hence considered as a key target to develop vaccines, antibodies and therapeutics. In this study, immunoinformatics approach was employed to design a novel multi-epitope vaccine using RBD of SARS-CoV-2 spike protein. The potential Band T-cell epitopes were selected from RBD sequence using various bioinformatics tools to design the vaccine construct. The in silico designed multi-epitope vaccine encompasses 146 amino acids with an adjuvant (human beta-defensin-2), which was further computationally evaluated for several parameters including antigenicity, allergenicity and stability. Subsequently, three-dimensional structure of vaccine construct was modelled and then docked with various toll-like receptors. Molecular dynamics (MD) study of docked TLR3-vaccine complex delineated it to be highly stable during simulation time and the stabilization of interaction was majorly contributed by electrostatic energy. The docked complex also showed low deformation and increased rigidity in motion of residues during dynamics. Furthermore, in silico cloning of the multi-epitope vaccine was carried out to generate the plasmid construct for expression in a bacterial system. Altogether, our study suggests that the designed vaccine candidate containing RBD region could provide the specific humoral and cell-mediated immune responses against SARS-CoV-2.

International Journal of Biological Macromolecules

International Journal of Biological Macromolecules

The enzyme pyridoxal kinase (PdxK) catalyzes the conversion of pyridoxal to pyridoxal-5'-phos... more The enzyme pyridoxal kinase (PdxK) catalyzes the conversion of pyridoxal to pyridoxal-5'-phosphate using ATP as the co-factor. The product pyridoxal-5'-phosphate (PLP) plays a key role in several biological processes such as transamination, decarboxylation and deamination. In the present study, full-length ORF of PdxK from Leishmania donovani (LdPdxK) was cloned and then purified using affinity chromatography. LdPdxK exists as a homo-dimer in solution and shows more activity at near to physiological pH. Biochemical analysis of LdPdxK with pyridoxal, pyridoxamine, pyridoxine and ginkgotoxin revealed its affinity preference towards different substrates. The secondary structure analysis using circular dichroism spectroscopy showed LdPdxK to be predominantly α-helical in organization which tends to decline at lower and higher pH. Simultaneously, LdPdxK was crystallized and its three dimensional structure in complex with ADP and different substrates were determined. Crystal structure of LdPdxK delineated that it has a central core of β-sheets surrounded by α-helices with a conserved GTGD ribokinase motif. The structures of LdPdxK disclosed no major structural changes between ADP and ADP- substrate bound structures. In addition, comparative structural analyses highlighted the key differences between the active site pockets of leishmanial and human PdxK, rendering LdPdxK an attractive candidate for the designing of novel and specific inhibitors.

Bioorganic Chemistry

In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthe... more In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthesized as galectin-1 targeting apoptosis inducing agents and evaluated for their in vitro cytotoxic potentials against a panel of selected human cancer cell lines namely, Brest (MCF7), Ovarian (SKOV3), Prostate (PC-3 & DU145) and normal embryonic kidney (HEK293T) cells, using MTT assay. Most of the compounds exhibited potent growth inhibitory action against the treated cancer cell lines with an IC50 range of 10-30 µM. Compound 7q exhibited a significant growth inhibition against prostate cancer (PC-3 & DU145) cell lines with an IC50 value of 7.45 ± 0.03 µM, 8.95 ± 0.17 µM respectively. Further, the target compound 7q was radiolabeled with fluorine-18 [18F] to be used as a novel PET radiotracer for imaging of tumors via targeting galectin-1, using appropriate reaction conditions in the GE Tracer-lab FX2N synthesis module. The purification of the [18F] radiolabeled compound [18F]-7q was successfully achieved with 60% ethanol. The radiochemical purity was>85% and residual solvent limits of DMF was 65 ± 3 ppm as analysed by HPLC, TLC & GC analytical methods. The apoptosis studies confirm the inhibition of cell proliferation with morphological changes like cell shrinkage, blebbing and cell wall deformation, increasing the ROS levels, and loss of mitochondrial membrane potential by Acridine orange/Ethidium bromide staining, Hoechst-33342 staining, H2DCFDA staining, annexin V-FITC/PI, and JC-1 staining methods. In flow cytometric analysis, 7q selectively arrested the sub-G1 phase of the cell cycle in a dose-dependent manner. In Gal-1 ELISA studies, compound 7q efficiently reduced the levels of Gal-1 protein in dose-dependent manner with an IC50 value of 100 µM. The binding constant (Ka) of 7q with Gal-1 was observed as 1.3 × 104 M-1 by fluorescence spectroscopy. The molecular docking studies clearly showed possible interactions and the pharmacokinetic (ADMET) properties of compound 7q with Gal-1. Hence, the novel 4, 7-disubstituted coumarins could be a potential cytotoxic and PET imaging agents via Gal-1.

European Journal of Medicinal Chemistry

Methionine aminopeptidase 1 of Leishmania donovani (LdMetAP1) is a novel antileishmanial target f... more Methionine aminopeptidase 1 of Leishmania donovani (LdMetAP1) is a novel antileishmanial target for its role in vital N-terminal methionine processing. After LdMetAP1 expression and purification, we employed a series of biochemical assays to determine optimal conditions for catalysis, metal dependence and substrate preferences for this ubiquitous enzyme. Screening of newly synthesized quinoline-carbaldehyde derivatives in inhibition assays led to the identification of HQ14 and HQ15 as novel and specific inhibitors for LdMetAP1 which compete with substrate for binding to the catalytic active site. Both leads bind LdMetAP1 with high affinity and possess druglikeness. Biochemical studies suggested HQ14 and HQ15 to be comparatively less effective against purified HsMetAP1 and showed no or less toxicity. We further show selectivity and inhibition of lead inhibitors is sensed through a non-catalytic Thr residue unique to LdMetAP1. Finally, structural studies highlight key differences in the binding modes of HQ14 and HQ15 to LdMetAP1 and HsMetAP1 providing structural basis for differences in inhibition. The study demonstrates the feasibility of deploying small drug like molecules to selectively target the catalytic activity of LdMetAP1 which may provide an effective treatment of leishmaniasis.

Biochimica et Biophysica Acta (BBA) - General Subjects

BACKGROUND M20 aminopeptidases, such as Peptidase T (PepT), are implicated in the hydrolysis of o... more BACKGROUND M20 aminopeptidases, such as Peptidase T (PepT), are implicated in the hydrolysis of oligopeptides during the terminal stages of protein degradation pathway to maintain turnover. Therefore, specific inhibition of PepT bores well for the development of novel next-generation antileishmanials. This work describes the metal dependence, substrate preferences and inhibition of PepT, and demonstrates in detail the role of its two conserved substrate binding residues. METHODS PepT was purified and characterized using a scheme of peptide substrates and peptidomimetic inhibitors. Residues T364 and N378 were mutated and characterized with an array of biochemical, biophysical and structural biology methods. RESULTS PepT sequence carries conserved motifs typical of M20 peptidases and our work on its biochemistry shows that this cytosolic enzyme carries broad substrate specificity with best cleavage preference for peptides carrying alanine at the P1 position. Peptidomimetics amastatin and actinonin occupied S1 pocket by competing with the substrate for binding to active site and inhibited PepT potently while arphamenine A and bestatin were less effective inhibitors. We further show that the mutation of conserved substrate binding residues (T364 and N378) to alanine affects structure, reduces substrate binding and alters the amidolytic activity of this dimeric enzyme. CONCLUSIONS PepT preferentially hydrolyzes oligopeptides carrying alanine at P1 position and is potently inhibited by peptidomimetics. Reduced substrate binding after mutations was a key factor involved in amidolytic digressions. GENERAL SIGNIFICANCE This study provides insights for further exploration of the druggability of PepT and highlights prospective applications of this enzyme along with its mutazyme T364A/N378A.

Indian Journal of Pharmaceutical Sciences

Gul, et al.: Antioxidant and Antiproliferative Activities of Artemisia nilagirica Medicinal plant... more Gul, et al.: Antioxidant and Antiproliferative Activities of Artemisia nilagirica Medicinal plants serve as unlimited source for phytoconstituents that possess potent antioxidant and antiproliferative properties. Artemisia nilagirica L. is a potent medicinal plant widely found in India and has been used to treat human diseases for centuries. The present investigation was conducted to investigate the antioxidant and antiproliferative abilities of different crude extracts of A. nilagirica. A detailed study was performed on the antioxidant activity and antiproliferative activity of the methanol extract of A. nilagirica by in vitro chemical analysis. The chemical composition of extracts, studied in terms of phenolics, total flavonoids, triterpenoids, tannins and alkaloids were also determined. Results suggested that the amounts of different phytoconstituents in extracts vary based on polarity of solvents. The extracts possessed different antioxidant and radical-scavenging activities in different assays. Among the extracts, ethyl acetate and alcohol extracts showed the most potent radical-scavenging activities. Ethyl acetate and alcohol extracts showed cytotoxicity towards eight different human cancer cell lines in vitro with IC 50 values ranging between 30.43±0.86 and 982.46±14.40 μg/ml and they were less toxic to normal cell lines. The findings of this study provide evidence that A. nilagirica extracts can be used potentially as ready accessible and valuable bioactive source for isolation of antioxidant and anticancer agents.

Nutrition and Cancer, 2016

Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of med... more Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of medicine. Therefore, the present study was designed to evaluate the effects of A. nilagirica extracts/fractions on inhibition of proliferation and apoptosis in a human monocytic leukemia (THP-1) cell line. The crude extracts (A. nilagirica ethyl acetate extract [ANE] and A. nilagirica methanolic extract [ANA]) showed cytotoxic activity toward THP-1 cells with the IC 50 values of 38.21 § 7.37 and 132.41 § 7.19 mg/ml, respectively. However, the cytotoxic activity of active fractions (ANE-B and ANM-9) obtained after column chromatography was found to be much more pronounced than their parent extracts. The IC 50 values of ANE-B and ANM-9 were found to be 27.04 § 2.54 mg/ml and 12.70 § 4.79 mg/ml, respectively, suggesting greater susceptibility of the malignant cells. Cell cycle analysis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) assay revealed that inhibition of cell growth by A. nilagirica fractions on THP-1 cells was mediated by apoptosis. Active fractions of A. nilagirica increased the expression levels of caspase-3, ¡7, and poly-ADP-ribose polymerase (PARP), a critical member of the apoptotic pathway. These results suggested that active fractions of A. nilagirica may play a promising role in growth suppression by inducing apoptosis in human monocytic leukemic cells via mitochondria-dependent and death receptordependent apoptotic pathways.

PLOS ONE, 2015

Nucleotide sequence polymorphisms among R gene alleles influence the process of coevolutionary in... more Nucleotide sequence polymorphisms among R gene alleles influence the process of coevolutionary interaction between host and pathogen by shaping the response of host plants towards invading pathogens. Here, we present the DNA sequence polymorphisms and diversities present among natural alleles of three rice bacterial blight resistance genes, Xa21, Xa26 and xa5. The diversity was examined across different wild relatives and cultivars of Oryza species. Functional significance of selected alleles was evaluated through semiquantitative reverse transcription polymerase chain reaction and real time PCR. The greatest nucleotide diversity and singleton variable sites (SVS) were present in Xa26 (π = 0.01958; SVS = 182) followed by xa5 and Xa21 alleles. The highest frequency of single nucleotide polymorphisms were observed in Xa21 alleles and least in xa5. Transition bias was observed in all the genes and 'G' to 'A' transitions were more favored than other form of transitions. Neutrality tests failed to show the presence of selection at these loci, though negative Tajima's D values indicate the presence of a rare form of polymorphisms. At the interspecies level, O. nivara exhibited more diversity than O. sativa. We have also identified two nearly identical resistant alleles of xa5 and two sequentially identical alleles of Xa21. The alleles of xa5 showed basal levels of expression while Xa21 alleles were functionally not expressed.

Malaria Journal, 2010

INVITED SPEAKER PRESENTATIONS I1 Development of an attenuated sporozoite vaccine to prevent and e... more INVITED SPEAKER PRESENTATIONS I1 Development of an attenuated sporozoite vaccine to prevent and eliminate Plasmodium falciparum malaria Peter F Billingsley ORAL PRESENTATIONS O1 Studies on the breeding swarms of Anopheles gambiae complex in malaria control perspective Benoît S Assogba O2 Variant surface antigens in cerebral malaria: distinct from others and similar to each other? Agnès Aubouy O3 Identification and characterization of novel Plasmodium falciparum cyclophilins and their roles in the antimalarial actions of cyclosporin A and derivatives Angus Bell O4 Development of a novel drug for uncomplicated malaria targeting the mitochondrial NADH:quinone oxidoreductase Giancarlo A Biagini O5 Larval time-to-hatch and insecticide resistance in the major malaria vector Anopheles gambiae from Ghana Basil D Brooke O6 Progress in the development of Reversed Chloroquine molecules as antimalarial therapy Steven J Burgess O7 Modeling the effects of vector control interventions in reducing malaria transmission, morbidity and mortality Konstantina Boutsika O8 A library of functional recombinant Plasmodium falciparum merozoite surface proteins Cecile Crosnier O9 Antimalarial activity of ulein and proof of its action on the Plasmodium falciparum digestive vacuole Alaíde Braga de Oliveira O10 A micro-bead device to explore Plasmodium falciparum-infected, spherocytic or aged red blood cells prone to mechanical retention by spleen endothelial slits Innocent Safeukui O11 Predicted impact of mosquito-stage transmission-blocking vaccines using an ensemble of microsimulations Aurelio Di Pasquale O12 Controlling malaria in Niger with bednets: how to take the Big Picture Duchemin Jean-Bernard O13 Adaptation of in vitro cytoadherence assay to Plasmodium knowlesi field isolates Farrah A Fatih O14 Molecular epidemiology of force of infection in malaria Ingrid Felger O15 Characterization and comparative sequence analyzes of GABA receptor gene in Asian main malaria mosquito, Anopheles stephensi Navid Dinparast Djadid O16 Refreshed approaches to the therapy of malaria-the case of natural medicine Hagai Ginsburg O17 Impact of protective haemoglobins C and S on P. falciparum malaria transmission in endemic area Louis C Gouagna O18 Household size explains successful malaria eradication Lena Hulden O19 Complete abrogation of sporozoite-induced sterile immunity by blood stage parasites of homologous and heterologous malaria species Megumi Inoue O20 A comprehensive survey of protein palmitoylation in late blood-stage Plasmodium falciparum Julian C Rayner O21 Wild chimpanzees are infected with homologous types of human malaria Marco Kaiser O22 Viral vectored transmission blocking vaccines against Plasmodium falciparum Melissa C Kapulu O23 What has been the contribution of the first Global Fund grant (2003-2006) to malaria control and health system strengthening in Timor-Leste? Joao Martins O24 Polyamine uptake in the malaria parasite, Plasmodium falciparum, is dependent on the parasite's membrane potential AI Louw O25 Stepwise dissection of Plasmodium falciparum merozoite invasion of the human erythrocyte Jake Baum O26 Identification of genetic markers of resistance to Artemisinin Combination Therapy in the rodent model Plasmodium chabaudi Louise A Rodrigues O27 The role of LCCL proteins in malaria transmission Sadia Saeed O28 Transfer of 4-hydroxynonenal, a inhibitory hemozoin (HZ) product, from HZ or HZ-laden phagocytes to developing human erythroid cells. A model for erythropoiesis inhibition in malaria anemia Paolo Arese O29 Sugar-fermenting yeast as an organic source of carbon dioxide to attract the malaria mosquito Anopheles gambiae s.s. Renate C Smallegange O30 Ancient out-of-Africa migration of Plasmodium falciparum along with modern humans Kazuyuki Tanabe O31 Intra-host dynamics of mixed species malaria parasite infections in mice and mosquitoes Richard Culleton O32 Investigating transcriptional regulation of Plasmodium falciparum upon drug perturbation Tharina van Brummlen POSTER PRESENTATIONS P1 Initial surveillance of suspected undesirable drug reactions to some Artemisinin-based combination therapies (ACTs) in Lagos, Nigeria Bamgboye M Afolabi, Antonia Dunkwu, A C Oparah P2 Plasmodium falciparum, vivax and malariae detection during the low transmission season in the hill tracts of Bangladesh

PLoS biology, Jan 5, 2018

Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resist... more Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice. HF inhibits IL-1β through general control nonderepressible 2 kinase (GCN2)-dependent activation of the cytoprotective integrated stress response (ISR) pathway, resulting in rerouting of IL-1β mRNA from translationally active polysomes to inactive ribocluster complexes-such as stress granules (SGs)-via recruitment of RNA-binding proteins (RBPs) T cell-restricted intracellular antigen-1(TIA-1)/TIA-1-related (TIAR), which are further cleared through induction of autophagy. GCN2 ablation resulted in reduced autophagy and SG formation, which is inversely correlated with IL-1β prod...

Scientific reports, Jan 20, 2016

Tuberculosis caused by Mycobacterium tuberculosis is a global encumbrance and it is estimated tha... more Tuberculosis caused by Mycobacterium tuberculosis is a global encumbrance and it is estimated that nearly one third population of the world acts as a reservoir for this pathogen without any symptoms. In this study, we attempted to characterise one of the genes of DosR regulon, Rv3131, a FMN binding nitroreductase domain containing protein, for its ability to alter cytokine profile, an essential feature of M. tuberculosis latency. Recombinant Rv3131 stimulated pro-inflammatory cytokines in THP-1 cells and human peripheral blood mononuclear cells in a time and dose dependent manner. In silico analyses using docking and simulations indicated that Rv3131 could strongly interact with TLR2 via a non-covalent bonding which was further confirmed using cell based colorimetric assay. In THP-1 cells treated with Rv3131 protein, a significant upsurge in the surface expression, overall induction and expression of mRNA of TLR2 was observed when analysed by flow cytometry, western blotting and rea...

Free Radicals and Antioxidants, 2018

Background: Artemisia absinthium is a valuable medicinal plant which has vast ethnopharmacologica... more Background: Artemisia absinthium is a valuable medicinal plant which has vast ethnopharmacological significance. Traditionally, it has been used to cure various ailments like fever, jaundice and other gastrointestinal problems in humans of ancient periods. Objective: The aim of the present study was to evaluate antioxidant and anti-proliferative properties of this medicinal plant. Methods: Total phenolics as well as flavonoid content in different extracts were estimated. Antioxidant activity was evaluated by metal (copper and iron) chelating ability and scavenging of free radicals (DPPH, ABTS, Nitric oxide, Hydroxyl, etc.). 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) assay was done for evaluation of the antiproliferative ability of the extracts. The Fourier Transform Infrared (FTIR) analysis was performed to identify the functional groups present in the metabolites in the different extracts. Results: Among all the extracts, Phenolic and flavonoid content was...

Mycobacterium tuberculosis, the cause of tuberculosis in humans, is present approximately in one ... more Mycobacterium tuberculosis, the cause of tuberculosis in humans, is present approximately in one third of the world's population, mostly in a dormant state. The proteins encoded by the dormancy survival regulon (DosR regulon) are mainly responsible for survival of the bacilli in a latent form. To maintain latency, mycobacteria orchestrate a balanced interplay of different cytokines secreted by immune cells during the granulomatous stage. The function of most of the DosR regulon proteins of M. tuberculosis is unknown. In this study, we have shown that one of the DosR regulon proteins, DATIN, encoded by the gene Rv0079, can stimulate macrophages and peripheral blood mononuclear cells (PBMC) to secrete important cytokines that may be significant in granuloma formation and its maintenance. The expression level of DATIN in Mycobacterium bovis BCG was found to be upregulated in pH stress and microaerobic conditions. Computational modeling, docking and simulation study suggested that DATIN might interact with TLR2. This was further confirmed through the interaction of recombinant DATIN with TLR2 expressed by HEK293 cells. When in vitro differentiated THP-1 cells were treated with recombinant DATIN, increased secretion of TNF-α, IL-1β and IL-8 was observed in a dose dependent manner. When differentiated THP-1 cells were infected with a modified BCG strain that overexpressed DATIN, augmented secretions of TNF-α, IL-1β and IL-8 were observed as compared to a reference BCG strain containing empty vector. Similarly, human PBMCs when infected with M. bovis BCG that overexpressed DATIN, upregulated secretion of proinflammatory cytokines IFN-γ, TNF-α, IL-1β and IL-8. The cytokine profiles dissected herein point to a possible role of DATIN in maintenance of latency with the help of the proinflammatory responses.

Mir Zahoor Gul, Sambamurthy Chandrasekaran*, Mohd Yasin Bhat, Radheshyam Maurya*, Insaf Ahmed Qur... more Mir Zahoor Gul, Sambamurthy Chandrasekaran*, Mohd Yasin Bhat, Radheshyam Maurya*, Insaf Ahmed Qureshi** and Irfan Ahmad Ghazi Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500 046, Telangana State, India *Department of Animal Biology, School of Life Sciences, University of Hyderabad,Gachibowli, Hyderabad 500 046, Telangana State, India **Department of Biotechnology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500 046, Telangana State, India

Novel coronavirus disease 2019 (COVID-19) emerges as a serious threat to public health globally. ... more Novel coronavirus disease 2019 (COVID-19) emerges as a serious threat to public health globally. The rapid spreading of COVID-19, caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), proclaimed the multitude of applied research needed not only to save the human health but also for the environmental safety. As per the recent World Health Organization reports, the novel corona virus may never be wiped out completely from the world. In this connection, the inhibitors already designed against different targets of previous human coronavirus (HCoV) infections will be a great starting point for further optimization. Pinpointing biochemical events censorious to the HCoV lifecycle has provided two proteases: a papain-like protease (PLpro) and a 3C-like protease (3CLpro) enzyme essential for viral replication. In this study, naphthyl derivatives inhibiting PLpro enzyme were subjected to robust molecular modelling approaches to understand different structural fingerpr...

showed four-bladed b-propeller structure having a pseudo 4-fold molecular symmetry along a metal ... more showed four-bladed b-propeller structure having a pseudo 4-fold molecular symmetry along a metal ion-binding central channel. The structure represents typical mammalian hemopexin fold with discernible features correlated with the possible functional variations. The protein was found to exist in the dimeric state. While LS-24 dimer binds to spermine in the crystal structure as well as in solution, binding of heme in solution resulted in the dissociation of the dimer into monomers with concomitant release of bound spermine. Interactions of heme and spermine with LS-24 bear physiological implications. While binding of spermine to LS-24 can be linked with polyamine biosynthesis that of heme correlates with oxidative stress. Mutually exclusive binding of heme and spermine in different oligomeric states suggest a role for LS-24 in sensing oxidative stress

Archives of Biochemistry and Biophysics

ACS Omega

A leucine aminopeptidase primarily hydrolyzes amino acid leucine from the N-terminus end of prote... more A leucine aminopeptidase primarily hydrolyzes amino acid leucine from the N-terminus end of proteins and is involved in free amino acid regulation, which makes it a potential therapeutic target against neglected tropical diseases including leishmaniasis. We here report the purification and characterization of the leucine aminopeptidase from Leishmania donovani (LdLAP). Using a set of biophysical and biochemical methods, we demonstrate that this enzyme was properly folded after expression in a bacterial system and catalytically active when supplemented with divalent metal cofactors with synthetic fluorogenic peptides. Subsequently, enzymatic inhibition assay denoted that LdLAP activity was inhibited by peptidomimetics, particularly actinonin, which caused potent inhibition and exhibited stronger binding association with the LdLAP. Stronger association of actinonin with the LdLAP was due to a stable complex formation mostly mediated by hydrogen bonding with catalytic and substrate-binding residues in the C-terminal catalytic domain. With molecular dynamics simulation studies, we demonstrate that peptidomimetics retain their topological space in the LdLAP catalytic pocket and form a stable complex. These results expand the current knowledge of aminopeptidase biochemistry and highlight that specific actinonin or peptidomimetic-based inhibitors may emerge as leads to combat leishmaniasis.

Journal of Biomolecular Structure and Dynamics

COVID-19, caused by SARS-CoV-2, is severe respiratory illnesses leading to millions of deaths wor... more COVID-19, caused by SARS-CoV-2, is severe respiratory illnesses leading to millions of deaths worldwide in very short span. The high case fatality rate and the lack of medical counter measures emphasize for an urgent quest to develop safe and effective vaccine. Receptor-binding domain (RBD) of spike protein of SARS-CoV-2 binds to the ACE2 receptor on human host cell for the viral attachment and entry, hence considered as a key target to develop vaccines, antibodies and therapeutics. In this study, immunoinformatics approach was employed to design a novel multi-epitope vaccine using RBD of SARS-CoV-2 spike protein. The potential Band T-cell epitopes were selected from RBD sequence using various bioinformatics tools to design the vaccine construct. The in silico designed multi-epitope vaccine encompasses 146 amino acids with an adjuvant (human beta-defensin-2), which was further computationally evaluated for several parameters including antigenicity, allergenicity and stability. Subsequently, three-dimensional structure of vaccine construct was modelled and then docked with various toll-like receptors. Molecular dynamics (MD) study of docked TLR3-vaccine complex delineated it to be highly stable during simulation time and the stabilization of interaction was majorly contributed by electrostatic energy. The docked complex also showed low deformation and increased rigidity in motion of residues during dynamics. Furthermore, in silico cloning of the multi-epitope vaccine was carried out to generate the plasmid construct for expression in a bacterial system. Altogether, our study suggests that the designed vaccine candidate containing RBD region could provide the specific humoral and cell-mediated immune responses against SARS-CoV-2.

International Journal of Biological Macromolecules

International Journal of Biological Macromolecules

The enzyme pyridoxal kinase (PdxK) catalyzes the conversion of pyridoxal to pyridoxal-5'-phos... more The enzyme pyridoxal kinase (PdxK) catalyzes the conversion of pyridoxal to pyridoxal-5'-phosphate using ATP as the co-factor. The product pyridoxal-5'-phosphate (PLP) plays a key role in several biological processes such as transamination, decarboxylation and deamination. In the present study, full-length ORF of PdxK from Leishmania donovani (LdPdxK) was cloned and then purified using affinity chromatography. LdPdxK exists as a homo-dimer in solution and shows more activity at near to physiological pH. Biochemical analysis of LdPdxK with pyridoxal, pyridoxamine, pyridoxine and ginkgotoxin revealed its affinity preference towards different substrates. The secondary structure analysis using circular dichroism spectroscopy showed LdPdxK to be predominantly α-helical in organization which tends to decline at lower and higher pH. Simultaneously, LdPdxK was crystallized and its three dimensional structure in complex with ADP and different substrates were determined. Crystal structure of LdPdxK delineated that it has a central core of β-sheets surrounded by α-helices with a conserved GTGD ribokinase motif. The structures of LdPdxK disclosed no major structural changes between ADP and ADP- substrate bound structures. In addition, comparative structural analyses highlighted the key differences between the active site pockets of leishmanial and human PdxK, rendering LdPdxK an attractive candidate for the designing of novel and specific inhibitors.

Bioorganic Chemistry

In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthe... more In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthesized as galectin-1 targeting apoptosis inducing agents and evaluated for their in vitro cytotoxic potentials against a panel of selected human cancer cell lines namely, Brest (MCF7), Ovarian (SKOV3), Prostate (PC-3 & DU145) and normal embryonic kidney (HEK293T) cells, using MTT assay. Most of the compounds exhibited potent growth inhibitory action against the treated cancer cell lines with an IC50 range of 10-30 µM. Compound 7q exhibited a significant growth inhibition against prostate cancer (PC-3 & DU145) cell lines with an IC50 value of 7.45 ± 0.03 µM, 8.95 ± 0.17 µM respectively. Further, the target compound 7q was radiolabeled with fluorine-18 [18F] to be used as a novel PET radiotracer for imaging of tumors via targeting galectin-1, using appropriate reaction conditions in the GE Tracer-lab FX2N synthesis module. The purification of the [18F] radiolabeled compound [18F]-7q was successfully achieved with 60% ethanol. The radiochemical purity was>85% and residual solvent limits of DMF was 65 ± 3 ppm as analysed by HPLC, TLC & GC analytical methods. The apoptosis studies confirm the inhibition of cell proliferation with morphological changes like cell shrinkage, blebbing and cell wall deformation, increasing the ROS levels, and loss of mitochondrial membrane potential by Acridine orange/Ethidium bromide staining, Hoechst-33342 staining, H2DCFDA staining, annexin V-FITC/PI, and JC-1 staining methods. In flow cytometric analysis, 7q selectively arrested the sub-G1 phase of the cell cycle in a dose-dependent manner. In Gal-1 ELISA studies, compound 7q efficiently reduced the levels of Gal-1 protein in dose-dependent manner with an IC50 value of 100 µM. The binding constant (Ka) of 7q with Gal-1 was observed as 1.3 × 104 M-1 by fluorescence spectroscopy. The molecular docking studies clearly showed possible interactions and the pharmacokinetic (ADMET) properties of compound 7q with Gal-1. Hence, the novel 4, 7-disubstituted coumarins could be a potential cytotoxic and PET imaging agents via Gal-1.

European Journal of Medicinal Chemistry

Methionine aminopeptidase 1 of Leishmania donovani (LdMetAP1) is a novel antileishmanial target f... more Methionine aminopeptidase 1 of Leishmania donovani (LdMetAP1) is a novel antileishmanial target for its role in vital N-terminal methionine processing. After LdMetAP1 expression and purification, we employed a series of biochemical assays to determine optimal conditions for catalysis, metal dependence and substrate preferences for this ubiquitous enzyme. Screening of newly synthesized quinoline-carbaldehyde derivatives in inhibition assays led to the identification of HQ14 and HQ15 as novel and specific inhibitors for LdMetAP1 which compete with substrate for binding to the catalytic active site. Both leads bind LdMetAP1 with high affinity and possess druglikeness. Biochemical studies suggested HQ14 and HQ15 to be comparatively less effective against purified HsMetAP1 and showed no or less toxicity. We further show selectivity and inhibition of lead inhibitors is sensed through a non-catalytic Thr residue unique to LdMetAP1. Finally, structural studies highlight key differences in the binding modes of HQ14 and HQ15 to LdMetAP1 and HsMetAP1 providing structural basis for differences in inhibition. The study demonstrates the feasibility of deploying small drug like molecules to selectively target the catalytic activity of LdMetAP1 which may provide an effective treatment of leishmaniasis.

Biochimica et Biophysica Acta (BBA) - General Subjects

BACKGROUND M20 aminopeptidases, such as Peptidase T (PepT), are implicated in the hydrolysis of o... more BACKGROUND M20 aminopeptidases, such as Peptidase T (PepT), are implicated in the hydrolysis of oligopeptides during the terminal stages of protein degradation pathway to maintain turnover. Therefore, specific inhibition of PepT bores well for the development of novel next-generation antileishmanials. This work describes the metal dependence, substrate preferences and inhibition of PepT, and demonstrates in detail the role of its two conserved substrate binding residues. METHODS PepT was purified and characterized using a scheme of peptide substrates and peptidomimetic inhibitors. Residues T364 and N378 were mutated and characterized with an array of biochemical, biophysical and structural biology methods. RESULTS PepT sequence carries conserved motifs typical of M20 peptidases and our work on its biochemistry shows that this cytosolic enzyme carries broad substrate specificity with best cleavage preference for peptides carrying alanine at the P1 position. Peptidomimetics amastatin and actinonin occupied S1 pocket by competing with the substrate for binding to active site and inhibited PepT potently while arphamenine A and bestatin were less effective inhibitors. We further show that the mutation of conserved substrate binding residues (T364 and N378) to alanine affects structure, reduces substrate binding and alters the amidolytic activity of this dimeric enzyme. CONCLUSIONS PepT preferentially hydrolyzes oligopeptides carrying alanine at P1 position and is potently inhibited by peptidomimetics. Reduced substrate binding after mutations was a key factor involved in amidolytic digressions. GENERAL SIGNIFICANCE This study provides insights for further exploration of the druggability of PepT and highlights prospective applications of this enzyme along with its mutazyme T364A/N378A.

Indian Journal of Pharmaceutical Sciences

Gul, et al.: Antioxidant and Antiproliferative Activities of Artemisia nilagirica Medicinal plant... more Gul, et al.: Antioxidant and Antiproliferative Activities of Artemisia nilagirica Medicinal plants serve as unlimited source for phytoconstituents that possess potent antioxidant and antiproliferative properties. Artemisia nilagirica L. is a potent medicinal plant widely found in India and has been used to treat human diseases for centuries. The present investigation was conducted to investigate the antioxidant and antiproliferative abilities of different crude extracts of A. nilagirica. A detailed study was performed on the antioxidant activity and antiproliferative activity of the methanol extract of A. nilagirica by in vitro chemical analysis. The chemical composition of extracts, studied in terms of phenolics, total flavonoids, triterpenoids, tannins and alkaloids were also determined. Results suggested that the amounts of different phytoconstituents in extracts vary based on polarity of solvents. The extracts possessed different antioxidant and radical-scavenging activities in different assays. Among the extracts, ethyl acetate and alcohol extracts showed the most potent radical-scavenging activities. Ethyl acetate and alcohol extracts showed cytotoxicity towards eight different human cancer cell lines in vitro with IC 50 values ranging between 30.43±0.86 and 982.46±14.40 μg/ml and they were less toxic to normal cell lines. The findings of this study provide evidence that A. nilagirica extracts can be used potentially as ready accessible and valuable bioactive source for isolation of antioxidant and anticancer agents.