Rumana Ahmad - Academia.edu (original) (raw)

Papers by Rumana Ahmad

Era's journal of medical research, Nov 30, 2023

The Ayurvedic community has long relied on this evergreen tropical plant for the treatment of inf... more The Ayurvedic community has long relied on this evergreen tropical plant for the treatment of inflammatory and intestinal conditions like colitis, hemorrhoids and even heart disorders.(5). Kokum has the potential to be used in the culinary, pharmaceutical and nutraceutical industries due to its abundance of bioactive compounds. The fruit is beneficial for the skin and also acts as a digestive tonic. The fruit has a lot of untapped potential due to its high nutrient density, medicinal properties and historical use. INTRODUCTION A HISTORICAL PERSPECTIVE Herbal medicines are the result of decades of therapeutic experience from generations of aboriginal medical practitioners. Garcinia indica Choisy (G.indica) Syn the popular plant Brindonia indica, also referred to as kokum and a member of the Guttiferae family, is indigenous to specific parts of India. Traditional Ayurvedic medicine has long used the plant because of its amazing healing properties for a broad variety of diseases (1). Originally confined to the western coast of the peninsula and the Western Ghats, Maharashtra, Karnataka, Goa and Kerala, it has also recently been discovered to grow in the eastern states of West Bengal, Assam and the North Eastern Hill region (2), (3). Traditional Ayurveda writings describe the unripe fruit of G. indicaas 'amla' (sour), whereas the ripe fruit is variously described as 'katu' (hot and spicy), 'kashaya' (p u n g e n t) , ' a l p a m a d h u r a ' (m i l d l y s w e e t) and'vranaropaka (enhanced healing of wounds) are properties of its bark and oil. 3-hydroxy citric acid found in the fruit rind has been shown to have fatburning effects. Additionally, it acts as an antidepressant and semen coagulant (4). The major phytochemicals extracted from kokum fruit with demonstrated physiological functions are hydroxycitric acid, anthocyanins and benzophenone derivatives (6). Other chemicals in the fruit include citric and oxalic acids. Carbohydrates, malic acid, polyphenols and ascorbic acid are the other main constituents. Kokum seed butter is utilized in many different types of moisturizers and cleansers because of its non-greasy moisturizing characteristics. Foot massage with kokum oil are really rejuvenating and relaxing. The fruit is additionally utilized as a spice as well as condiment in many different pickles, chutneys, and curry meals in India. 'Amrutkokum', a sugar syrup-steeped fruit beverage used to treat sunstroke, is a summertime staple (7). The present provides an update on the anticancer, antibacterial, antidiabetic, antiobesity, antidepressant and antiulcer properties of G. indica, besides its multiple uses in the culinary and industries.

Era's Journal of Medical Research, 2019

Matrix metalloproteases (MMPs) are involved in the dissolution of basement membrane and component... more Matrix metalloproteases (MMPs) are involved in the dissolution of basement membrane and components of extracellular matrix (ECM). Metastasis is one of the leading causes of deaths in cancer. It is a critical step in the progression of cancer through dissolution of tissue barriers throughout the body and spread to distant sites. MMPs induce cancer progression by interacting with tumor suppressor genes and initiating abnormalities in normal cells. The regulation of MMPs is critical, since they have a role in tumorigenesis and metastasis. One of the most effective therapeutic strategies to overcome cancer progression is through downregulation of the expression of MMPs leading to anti-invasion and anti-metastasis. Tissue inhibitors of metalloproteinases (TIMPs) are the major in situ inhibitors of MMPs and they maintain homeostasis between ECM formation and destruction. However, TIMPs have limited efficacy as pharmacological agents due to their short halflives in vivo. In the present review, the classification of MMPs and their significant roles in different types of cancers have been discussed. A number of synthetic MMP inhibitors (MMPIs) have been synthesized in the last few decades and have undergone rigorous clinical evaluation in an attempt to control abnormal MMPs expression in certain physiological conditions including cancer. Although limited success has been achieved in this respect, nevertheless, development of novel and effective MMPIs is an ongoing area of vigorous research and might prove to be a promising research area for both diagnostic and therapeutic purposes in future.

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormali... more Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. <i>Withania somnifera</i> (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using <i>in silico</i> methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted t...

Thiosemicarbazones are Schiff based ligands which have gained importance over the decades as pote... more Thiosemicarbazones are Schiff based ligands which have gained importance over the decades as potential drug candidates. When coordinated to metals, they have proved as good anticancer, antimicrobial, antioxidant and antiprotozoal agents. Numerous applications of these ligands in the field of Analytical Chemistry have also been reported. The present review aims to summarize some of the recent advances in the design/synthesis of novel substituted metal-ligand thiosemicarbazone complexes with special emphasis on the efficacy of transition metalligand complexes as potential anticancer agents as well as to unravel their possible mode of action on in vitro living systems viz. cell lines as well as a few animal models. Transition-metal based complexes hold several advantages over other metal complexes because of their better acceptability and low toxicity in biological systems. Moreover, the role of transition metals as micronutrients as well as co-factors of several metallo-enzymes in liv...

A series of six Cu (II) complexes were prepared from N4 substituted thiosemicarbazones having str... more A series of six Cu (II) complexes were prepared from N4 substituted thiosemicarbazones having structures [Cu (p-clbhtsc)2 ]Cl2. 2H2O [1], [Cu (p-mbhtsc)2]Cl2.2H2O [2], [Cu (p-nbhtsc)2]Cl2.2H2O [3], [Cu (p-clacehtsc)2 ]Cl2. 2H2O [4], [Cu (pmacehtsc) 2]Cl2.2H2O [5] and [Cu (p-nacehtsc)2]Cl2.2H2O [6] where (p-clbhtsc)=p-chlorobenzylidene thiosemicarbazone, (pmbhtsc)= p-methoxy benzylidene thiosemicarbazone, (p-nbhtsc)=p-nitro benzylidene thiosemicarbazone, (p-clacehtsc)=pchloroacetophenone thiosemicarbazone, (p-macehtsc)=p-methoxyacetophenone thiosemicarbazone, and (p-nacehtsc)=pnitroacetophenone thiosemicarbazone. All six complexes were characterized by elemental analysis, IR, 1HNMR, mass and electronic spectra. The magnetic moments and electronic spectral studies suggested distorted octahedral geometry for all the complexes. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding through azomethine nitrogen and sulfur atom. Cytotoxic activity against human breas...

Journal of Biomolecular Structure and Dynamics, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coro... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). Nigella sativa, commonly known as black seed or black cumin, has been a historical and traditional plant since thousands of years. Based on their therapeutic efficacy, the chief components of terpenoids and flavonoids were selected from N. sativa seeds and seed oil. This study was designed to check the antiviral efficacy of N. sativa main phytoconstituents against five potential targets of SARS-CoV-2 using in silico structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins viz. N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-PRO ; PDB ID: 6W9C) of SARS-CoV-2 using AutoDock 4.2.6, AutoDock Vina and iGEMDOCK. PASS analyses of all ten phytocomponents using Lipinski's Rule of five showed promising results. Further, druglikeness and toxicity assessment using OSIRIS Data Warrior v5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Molecular dynamics simulation study of NRBD of SARS-CoV-2 nucleocapsid protein-alpha-spinasterol complex and PL-PRO-cycloeucalenol complex displayed strong stability at 300 K. Both these complexes exhibited constant root mean square deviation (RMSDs) of protein side chains and Ca atoms throughout the simulation run time. Interestingly, PL-PRO and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL-PRO have the potential to serve as therapeutic targets for N. sativa phytoconstituents in drug discovery process against COVID-19.

Journal of Biomolecular Structure and Dynamics, 2021

There is currently a dearth of specific therapies to treat respiratory infections caused by the t... more There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo. Communicated by Ramaswamy H. Sarma.

Indian Journal of Clinical Biochemistry, 2021

Background:Ajwa date (Phoenix dactylifera L.) has been described in traditional and alternative m... more Background:Ajwa date (Phoenix dactylifera L.) has been described in traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remain to be scientifically validated. In the present study, we evaluated the anticancer effects of the ethanolic extract of Ajwa Dates pulp on human triple-negative breast cancer MDA-MB-231 cells. MethodsAjwa Dates Pulp Extract (ADPE) was phytochemically characterized using high performance liquid chromatography coupled with mass spectrometry (LC-MS). The in vitro cytotoxicity of ADPE at various concentrations viz. 10, 12, 15, 18, 20, 22 and 25 mg/mL were evaluated against MDA-MB-231 and MCF-7 cells at 24 and 48 h. The apoptosis effect was examined by Hoechst 33342 and AO/PI-double-stain using fluorescence microscopy. The proportion of apoptotic cells, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) and cell cycle phase distri...

Future Medicinal Chemistry, 2020

Aim: Phenanthridines are an essential class of nitrogenous heterocycles with extensive applicatio... more Aim: Phenanthridines are an essential class of nitrogenous heterocycles with extensive applications in medicinal chemistry. The development of efficient and eco-friendly methods for the preparation of chirally pure dihydropyrrolo[1,2- f]phenanthridines (5a–h), and their in vitro evaluation and modeling studies as potential anticancer, antioxidant and DNA cleavage agents is reported. Methodology & results: Compounds 5a–h were prepared through a facile one-pot synthesis and characterized by infrared, high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance. The molecules were subjected to virtual screening and docking analysis against selected human molecular targets. Compound 5g displayed good binding properties as well as significant anticancer and DNA cleavage activity. Conclusion: Compound 5g has been identified as a potential lead candidate for further testing against additional cancer cell lines and animal models in future.

Journal of Biomolecular Structure and Dynamics, 2020

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormali... more Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. Withania somnifera (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using in silico methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted to undergo Phase-I metabolism prior to excretion. All phytoconstituents had favorable bioactivity scores with respect to various receptor proteins and target enzymes. SAR analysis revealed that the number of oxygen atoms in the withanolide backbone and structural rearrangements were crucial for effective binding. Molecular simulation analyses of SARS-CoV-2 spike protein and papain-like protease with Withanolides A and B, respectively, displayed a stability profile at 300 K and constant RMSDs of protein side chains and Ca atoms throughout the simulation run time. In a nutshell, WS phytoconstituents warrant further investigations in vitro and in vivo to unravel their molecular mechanism(s) and modes of action for their future development as novel antiviral agents against COVID-19.

Cytopathology, 2020

Micronuclei counts were performed in cervical smears with low‐grade squamous intraepithelial lesi... more Micronuclei counts were performed in cervical smears with low‐grade squamous intraepithelial lesions of the cervix (LSIL) to assess its potentiality as tumour marker in cervical carcinogenesis.

Era's Journal of Medical Research, 2019

Various experiments have proved that Curcuma longa (CL), the Golden Spice of our kitchen, exibits... more Various experiments have proved that Curcuma longa (CL), the Golden Spice of our kitchen, exibits anticancer effects to inhibit the uncontrolled cell division and metastasis of carcinoma cells, by the cell cycle arrest and finally promote to programmed cell death. In particular, CL exhibits the most powerful phytocompound to affect human breast cancer, the most prevalent type of cancer among the women, throughout the world. The main compounds present in CL can be classified as Curcuminoids and Non-curcuminoids, which shows the anticancer, anti-inflamatory functions for cancer cells. It helps in powerful inhibition in low concentration on breast cancer cell lines that exhibit the estrogen receptor negative(ER) and sensitizes the cells towards the anticancer drugs in low dose. Above all, it promotes the cells towards apoptosis, which does not have hormone receptor expression. Curcuminoids and non curcuminoids inhibit the excessive cell division of breast cancer stem cells (BCSC). Prevention of BCSC proliferation is performed by suppressing metastasis and adherence of the cells with one another, ultimately limiting tumor formation. The main powerful phyto-compound present in CL, curcumin, causes the yellow coloration of it, has drawn the main interest as the chemosensitizing agent also. Different mode of cancer cell targeting and apoptosis is discussed.

Era's Journal of Medical Research, 2019

Matrix metalloproteinases (MMPs) are members of metzincin group of zincdependent endopeptidases w... more Matrix metalloproteinases (MMPs) are members of metzincin group of zincdependent endopeptidases which are responsible for degrading and remodeling of extracellular matrix (ECM) during organogenesis, wound healing, angiogenesis, apoptosis, cell proliferation and cancer progression. MMPs are synthesized in cytoplasm as proenzymes with a cytoplasmic domain and can be divided into 6 groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type and other non-classified MMPs. They are found in cytosol, subcellular organelles, nucleus and extracellular regions and have several biological functions in all stages of cancer. MMPs play crucial roles in cell growth, survival, differentiation and motility. ECM degradation by MMPs not only increases tumor invasion but also affects tumor cell behavior and leads to metastasis and cancer progression. Thus, MMPs and their inhibitors can be considered as promising therapeutic target(s) against cancer.

Scientific Reports, 2019

Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several... more Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosisinducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide β-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose-and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/ PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer. Cancer is a rapidly growing health problem around the world, caused mainly due to mutation, adverse environmental conditions, dietary habits, and lifestyle 1,2. Amongst cancer, hepatocellular carcinoma (HCC) is the second most common cause of cancer death. HCC is the fifth most common malignant tumor of the liver in adults and occurs predominantly in patients with underlying chronic liver disease and cirrhosis 3. Due to HCC, there are approximately 800,000 deaths per annum globally 4. The prevalence of HCC is increasing gradually in the world during the past decade 5. Various treatment strategies based on hepatic resection, orthotopic liver transplantation, chemo-embolization and systemic chemotherapies 6 , are available. Amongst all treatment managements, chemotherapy is the main therapeutic method for advanced HCC. However, drug resistance and side-effects of liver failure accompanying the disease limit the successful outcome in most cases 7. In this context, natural products may be considered as safe and effective alternative therapeutic methods for the treatment of HCC and hence, it is essential to rigorously explore novel natural products that effectively cure HCC patients. Ethno-traditional uses of plant-derived natural products have been a major source for the discovery of potential anticancer agents 8. Natural products are primary sources of effective anticancer drugs with novel structures and unique mechanisms of action for the treatment of various forms of cancer 9. Various plant-derived natural products such as alkaloids, flavonoids, polysaccharides, saponins, and terpenes have been used against HCC 10. However, most of the plant-derived natural products are toxic or ineffective which limit the use of natural

Computational biology and chemistry, 2018

The present paper deals with in silico evaluation of 32 virtually designed transition metal compl... more The present paper deals with in silico evaluation of 32 virtually designed transition metal complexes of 2-butanone thiosemicarbazone and N,S,O containing donor hetero-ligands namely py, bpy, furan, thiophene, 2-picoline, 1,10-phenanthroline, piperazine and liquid ammonia. The complexes were designed with a view to assess their potential anticancer, antioxidant and antibacterial activity. The absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the chosen ligands were calculated by admetSAR software. Metabolic sites of different ligands likely to undergo metabolism were predicted using Metaprint 2D. The proposed complexes were also evaluated for their drug-like quality based on Lipinski's, Veber, Ghose and leadlikeness filters. Druglikeness and toxicity potential were predicted by OSIRIS property explorer. The pharmacokinetic properties and bioactivity scores were calculated by Molinspiration tool. Bioactivity scores of the complexes were predicted ...

Journal of ethnopharmacology, Jan 22, 2018

India being a multicultural nation, every region of the country offers a distinct culinary flavor... more India being a multicultural nation, every region of the country offers a distinct culinary flavor and taste. These flavors are attributed to spices and condiments which form the mainstay of Indian cuisine. Most of these spices and condiments are derived from various biodiversity hotspots in India and form the crux of India's multidiverse and multicultural cuisine. Apart from their varying aromas, flavors and tastes, these spices and condiments are known to possess several medicinal properties also. Most of these spices find considerable mention in Ayurveda, the indigenous system of medicine, as panaceas for several aliments. Cinnamomum zeylanicum (CZ), belonging to family Lauraceae and commonly known as cinnamon is one such spice known to have diverse medicinal properties since time immemorial. In the present study, apoptotic and anti-microbial activity of ethanolic extract of CZ was evaluated against human breast cancer cell line MDA-MB-231 and compared for its effect on normal...

Journal of chemical biology, 2017

2-Butanone thiosemicarbazone ligand was prepared by condensation reaction between thiosemicarbazi... more 2-Butanone thiosemicarbazone ligand was prepared by condensation reaction between thiosemicarbazide and butanone. The ligand was characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry and UV spectroscopic studies. Docking studies were performed to study inhibitory action against topoisomerase II (Topo II) and ribonucleoside diphosphate reductase (RR) enzymes. Inhibition constants (Ki ) of the ligand were 437.87 and 327.4 μM for the two enzymes, respectively. The ligand was tested for its potential anticancer activity against two cancer cell lines MDA-MB-231 and A549 using MTT assay and was found to exhibit good activity at higher doses with an IC50 = 80 μM against human breast cancer cell line MDA-MB-231. On the other hand, no significant activity was obtained against the lung carcinoma cell line A549. Antibacterial activity of the ligand was tested against Staphylococcus aureus and E. coli using the disc diffusion method. Ligand did not exhibit any significant antibacterial...

Journal of Ayurveda and integrative medicine, Jan 6, 2017

The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian tradi... more The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian traditional system of medicine. Withania somnifera Dunal and Withania coagulans Dunal have been documented in folklore as panaceas for various ailments since time immemorial. W. coagulans (WC), commonly called as Indian cheese maker is used for fermenting milk for cheese production in various parts of India. In the study, in vitro cytotoxicity of methanolic extract of dried fruits (berries) of WC was evaluated in a dose dependent manner using trypan blue dye exclusion method against human breast cancer cell line MDA-MB-231 and normal kidney epithelial cell line Vero in the range 20-200 μg/ml. The percentage viability of the cell lines was determined by using MTT assay and cytometry. Methanolic extract of WC showed significant anticancer activity against MDA-MB-231 cell line. Cell viability was reduced to about 50% at 40 μg/ml of methanolic extract in 50% DMSO. Cytotoxicity of the extract was ...

Integrative medicine research, 2017

Aromatherapy is used in clinical settings for patients suffering from several chronic and critica... more Aromatherapy is used in clinical settings for patients suffering from several chronic and critical diseases such as cancer. Ethyl acetate (EA) is a colorless liquid with a characteristic fruity smell and is naturally present in fruits and wines. In the present study, the effect of the aroma of EA was evaluated on human breast cancer cell line MDA-MB-231 and normal cell line, Vero. Cell line viability and mechanism of EA cytotoxicity were determined by Trypan blue dye exclusion assay and phase contrast microscopy. It was found that EA at a concentration of 0.026 M was effective in causing considerable cytotoxicity in breast cancer cells (without even coming in contact with the culture medium and cells), while showing no effect on normal cells. Mechanism of action of EA on cancer and Vero cells was investigated by DNA fragmentation and dye binding assays using agarose gel electrophoresis (AGE) and fluorescence microscopy/cytometry, respectively. It was found that EA aroma induced pred...

Era's journal of medical research, Nov 30, 2023

The Ayurvedic community has long relied on this evergreen tropical plant for the treatment of inf... more The Ayurvedic community has long relied on this evergreen tropical plant for the treatment of inflammatory and intestinal conditions like colitis, hemorrhoids and even heart disorders.(5). Kokum has the potential to be used in the culinary, pharmaceutical and nutraceutical industries due to its abundance of bioactive compounds. The fruit is beneficial for the skin and also acts as a digestive tonic. The fruit has a lot of untapped potential due to its high nutrient density, medicinal properties and historical use. INTRODUCTION A HISTORICAL PERSPECTIVE Herbal medicines are the result of decades of therapeutic experience from generations of aboriginal medical practitioners. Garcinia indica Choisy (G.indica) Syn the popular plant Brindonia indica, also referred to as kokum and a member of the Guttiferae family, is indigenous to specific parts of India. Traditional Ayurvedic medicine has long used the plant because of its amazing healing properties for a broad variety of diseases (1). Originally confined to the western coast of the peninsula and the Western Ghats, Maharashtra, Karnataka, Goa and Kerala, it has also recently been discovered to grow in the eastern states of West Bengal, Assam and the North Eastern Hill region (2), (3). Traditional Ayurveda writings describe the unripe fruit of G. indicaas 'amla' (sour), whereas the ripe fruit is variously described as 'katu' (hot and spicy), 'kashaya' (p u n g e n t) , ' a l p a m a d h u r a ' (m i l d l y s w e e t) and'vranaropaka (enhanced healing of wounds) are properties of its bark and oil. 3-hydroxy citric acid found in the fruit rind has been shown to have fatburning effects. Additionally, it acts as an antidepressant and semen coagulant (4). The major phytochemicals extracted from kokum fruit with demonstrated physiological functions are hydroxycitric acid, anthocyanins and benzophenone derivatives (6). Other chemicals in the fruit include citric and oxalic acids. Carbohydrates, malic acid, polyphenols and ascorbic acid are the other main constituents. Kokum seed butter is utilized in many different types of moisturizers and cleansers because of its non-greasy moisturizing characteristics. Foot massage with kokum oil are really rejuvenating and relaxing. The fruit is additionally utilized as a spice as well as condiment in many different pickles, chutneys, and curry meals in India. 'Amrutkokum', a sugar syrup-steeped fruit beverage used to treat sunstroke, is a summertime staple (7). The present provides an update on the anticancer, antibacterial, antidiabetic, antiobesity, antidepressant and antiulcer properties of G. indica, besides its multiple uses in the culinary and industries.

Era's Journal of Medical Research, 2019

Matrix metalloproteases (MMPs) are involved in the dissolution of basement membrane and component... more Matrix metalloproteases (MMPs) are involved in the dissolution of basement membrane and components of extracellular matrix (ECM). Metastasis is one of the leading causes of deaths in cancer. It is a critical step in the progression of cancer through dissolution of tissue barriers throughout the body and spread to distant sites. MMPs induce cancer progression by interacting with tumor suppressor genes and initiating abnormalities in normal cells. The regulation of MMPs is critical, since they have a role in tumorigenesis and metastasis. One of the most effective therapeutic strategies to overcome cancer progression is through downregulation of the expression of MMPs leading to anti-invasion and anti-metastasis. Tissue inhibitors of metalloproteinases (TIMPs) are the major in situ inhibitors of MMPs and they maintain homeostasis between ECM formation and destruction. However, TIMPs have limited efficacy as pharmacological agents due to their short halflives in vivo. In the present review, the classification of MMPs and their significant roles in different types of cancers have been discussed. A number of synthetic MMP inhibitors (MMPIs) have been synthesized in the last few decades and have undergone rigorous clinical evaluation in an attempt to control abnormal MMPs expression in certain physiological conditions including cancer. Although limited success has been achieved in this respect, nevertheless, development of novel and effective MMPIs is an ongoing area of vigorous research and might prove to be a promising research area for both diagnostic and therapeutic purposes in future.

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormali... more Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. <i>Withania somnifera</i> (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using <i>in silico</i> methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted t...

Thiosemicarbazones are Schiff based ligands which have gained importance over the decades as pote... more Thiosemicarbazones are Schiff based ligands which have gained importance over the decades as potential drug candidates. When coordinated to metals, they have proved as good anticancer, antimicrobial, antioxidant and antiprotozoal agents. Numerous applications of these ligands in the field of Analytical Chemistry have also been reported. The present review aims to summarize some of the recent advances in the design/synthesis of novel substituted metal-ligand thiosemicarbazone complexes with special emphasis on the efficacy of transition metalligand complexes as potential anticancer agents as well as to unravel their possible mode of action on in vitro living systems viz. cell lines as well as a few animal models. Transition-metal based complexes hold several advantages over other metal complexes because of their better acceptability and low toxicity in biological systems. Moreover, the role of transition metals as micronutrients as well as co-factors of several metallo-enzymes in liv...

A series of six Cu (II) complexes were prepared from N4 substituted thiosemicarbazones having str... more A series of six Cu (II) complexes were prepared from N4 substituted thiosemicarbazones having structures [Cu (p-clbhtsc)2 ]Cl2. 2H2O [1], [Cu (p-mbhtsc)2]Cl2.2H2O [2], [Cu (p-nbhtsc)2]Cl2.2H2O [3], [Cu (p-clacehtsc)2 ]Cl2. 2H2O [4], [Cu (pmacehtsc) 2]Cl2.2H2O [5] and [Cu (p-nacehtsc)2]Cl2.2H2O [6] where (p-clbhtsc)=p-chlorobenzylidene thiosemicarbazone, (pmbhtsc)= p-methoxy benzylidene thiosemicarbazone, (p-nbhtsc)=p-nitro benzylidene thiosemicarbazone, (p-clacehtsc)=pchloroacetophenone thiosemicarbazone, (p-macehtsc)=p-methoxyacetophenone thiosemicarbazone, and (p-nacehtsc)=pnitroacetophenone thiosemicarbazone. All six complexes were characterized by elemental analysis, IR, 1HNMR, mass and electronic spectra. The magnetic moments and electronic spectral studies suggested distorted octahedral geometry for all the complexes. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding through azomethine nitrogen and sulfur atom. Cytotoxic activity against human breas...

Journal of Biomolecular Structure and Dynamics, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coro... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). Nigella sativa, commonly known as black seed or black cumin, has been a historical and traditional plant since thousands of years. Based on their therapeutic efficacy, the chief components of terpenoids and flavonoids were selected from N. sativa seeds and seed oil. This study was designed to check the antiviral efficacy of N. sativa main phytoconstituents against five potential targets of SARS-CoV-2 using in silico structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins viz. N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-PRO ; PDB ID: 6W9C) of SARS-CoV-2 using AutoDock 4.2.6, AutoDock Vina and iGEMDOCK. PASS analyses of all ten phytocomponents using Lipinski's Rule of five showed promising results. Further, druglikeness and toxicity assessment using OSIRIS Data Warrior v5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Molecular dynamics simulation study of NRBD of SARS-CoV-2 nucleocapsid protein-alpha-spinasterol complex and PL-PRO-cycloeucalenol complex displayed strong stability at 300 K. Both these complexes exhibited constant root mean square deviation (RMSDs) of protein side chains and Ca atoms throughout the simulation run time. Interestingly, PL-PRO and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL-PRO have the potential to serve as therapeutic targets for N. sativa phytoconstituents in drug discovery process against COVID-19.

Journal of Biomolecular Structure and Dynamics, 2021

There is currently a dearth of specific therapies to treat respiratory infections caused by the t... more There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo. Communicated by Ramaswamy H. Sarma.

Indian Journal of Clinical Biochemistry, 2021

Background:Ajwa date (Phoenix dactylifera L.) has been described in traditional and alternative m... more Background:Ajwa date (Phoenix dactylifera L.) has been described in traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remain to be scientifically validated. In the present study, we evaluated the anticancer effects of the ethanolic extract of Ajwa Dates pulp on human triple-negative breast cancer MDA-MB-231 cells. MethodsAjwa Dates Pulp Extract (ADPE) was phytochemically characterized using high performance liquid chromatography coupled with mass spectrometry (LC-MS). The in vitro cytotoxicity of ADPE at various concentrations viz. 10, 12, 15, 18, 20, 22 and 25 mg/mL were evaluated against MDA-MB-231 and MCF-7 cells at 24 and 48 h. The apoptosis effect was examined by Hoechst 33342 and AO/PI-double-stain using fluorescence microscopy. The proportion of apoptotic cells, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) and cell cycle phase distri...

Future Medicinal Chemistry, 2020

Aim: Phenanthridines are an essential class of nitrogenous heterocycles with extensive applicatio... more Aim: Phenanthridines are an essential class of nitrogenous heterocycles with extensive applications in medicinal chemistry. The development of efficient and eco-friendly methods for the preparation of chirally pure dihydropyrrolo[1,2- f]phenanthridines (5a–h), and their in vitro evaluation and modeling studies as potential anticancer, antioxidant and DNA cleavage agents is reported. Methodology & results: Compounds 5a–h were prepared through a facile one-pot synthesis and characterized by infrared, high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance. The molecules were subjected to virtual screening and docking analysis against selected human molecular targets. Compound 5g displayed good binding properties as well as significant anticancer and DNA cleavage activity. Conclusion: Compound 5g has been identified as a potential lead candidate for further testing against additional cancer cell lines and animal models in future.

Journal of Biomolecular Structure and Dynamics, 2020

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormali... more Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. Withania somnifera (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using in silico methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted to undergo Phase-I metabolism prior to excretion. All phytoconstituents had favorable bioactivity scores with respect to various receptor proteins and target enzymes. SAR analysis revealed that the number of oxygen atoms in the withanolide backbone and structural rearrangements were crucial for effective binding. Molecular simulation analyses of SARS-CoV-2 spike protein and papain-like protease with Withanolides A and B, respectively, displayed a stability profile at 300 K and constant RMSDs of protein side chains and Ca atoms throughout the simulation run time. In a nutshell, WS phytoconstituents warrant further investigations in vitro and in vivo to unravel their molecular mechanism(s) and modes of action for their future development as novel antiviral agents against COVID-19.

Cytopathology, 2020

Micronuclei counts were performed in cervical smears with low‐grade squamous intraepithelial lesi... more Micronuclei counts were performed in cervical smears with low‐grade squamous intraepithelial lesions of the cervix (LSIL) to assess its potentiality as tumour marker in cervical carcinogenesis.

Era's Journal of Medical Research, 2019

Various experiments have proved that Curcuma longa (CL), the Golden Spice of our kitchen, exibits... more Various experiments have proved that Curcuma longa (CL), the Golden Spice of our kitchen, exibits anticancer effects to inhibit the uncontrolled cell division and metastasis of carcinoma cells, by the cell cycle arrest and finally promote to programmed cell death. In particular, CL exhibits the most powerful phytocompound to affect human breast cancer, the most prevalent type of cancer among the women, throughout the world. The main compounds present in CL can be classified as Curcuminoids and Non-curcuminoids, which shows the anticancer, anti-inflamatory functions for cancer cells. It helps in powerful inhibition in low concentration on breast cancer cell lines that exhibit the estrogen receptor negative(ER) and sensitizes the cells towards the anticancer drugs in low dose. Above all, it promotes the cells towards apoptosis, which does not have hormone receptor expression. Curcuminoids and non curcuminoids inhibit the excessive cell division of breast cancer stem cells (BCSC). Prevention of BCSC proliferation is performed by suppressing metastasis and adherence of the cells with one another, ultimately limiting tumor formation. The main powerful phyto-compound present in CL, curcumin, causes the yellow coloration of it, has drawn the main interest as the chemosensitizing agent also. Different mode of cancer cell targeting and apoptosis is discussed.

Era's Journal of Medical Research, 2019

Matrix metalloproteinases (MMPs) are members of metzincin group of zincdependent endopeptidases w... more Matrix metalloproteinases (MMPs) are members of metzincin group of zincdependent endopeptidases which are responsible for degrading and remodeling of extracellular matrix (ECM) during organogenesis, wound healing, angiogenesis, apoptosis, cell proliferation and cancer progression. MMPs are synthesized in cytoplasm as proenzymes with a cytoplasmic domain and can be divided into 6 groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type and other non-classified MMPs. They are found in cytosol, subcellular organelles, nucleus and extracellular regions and have several biological functions in all stages of cancer. MMPs play crucial roles in cell growth, survival, differentiation and motility. ECM degradation by MMPs not only increases tumor invasion but also affects tumor cell behavior and leads to metastasis and cancer progression. Thus, MMPs and their inhibitors can be considered as promising therapeutic target(s) against cancer.

Scientific Reports, 2019

Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several... more Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosisinducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide β-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose-and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/ PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer. Cancer is a rapidly growing health problem around the world, caused mainly due to mutation, adverse environmental conditions, dietary habits, and lifestyle 1,2. Amongst cancer, hepatocellular carcinoma (HCC) is the second most common cause of cancer death. HCC is the fifth most common malignant tumor of the liver in adults and occurs predominantly in patients with underlying chronic liver disease and cirrhosis 3. Due to HCC, there are approximately 800,000 deaths per annum globally 4. The prevalence of HCC is increasing gradually in the world during the past decade 5. Various treatment strategies based on hepatic resection, orthotopic liver transplantation, chemo-embolization and systemic chemotherapies 6 , are available. Amongst all treatment managements, chemotherapy is the main therapeutic method for advanced HCC. However, drug resistance and side-effects of liver failure accompanying the disease limit the successful outcome in most cases 7. In this context, natural products may be considered as safe and effective alternative therapeutic methods for the treatment of HCC and hence, it is essential to rigorously explore novel natural products that effectively cure HCC patients. Ethno-traditional uses of plant-derived natural products have been a major source for the discovery of potential anticancer agents 8. Natural products are primary sources of effective anticancer drugs with novel structures and unique mechanisms of action for the treatment of various forms of cancer 9. Various plant-derived natural products such as alkaloids, flavonoids, polysaccharides, saponins, and terpenes have been used against HCC 10. However, most of the plant-derived natural products are toxic or ineffective which limit the use of natural

Computational biology and chemistry, 2018

The present paper deals with in silico evaluation of 32 virtually designed transition metal compl... more The present paper deals with in silico evaluation of 32 virtually designed transition metal complexes of 2-butanone thiosemicarbazone and N,S,O containing donor hetero-ligands namely py, bpy, furan, thiophene, 2-picoline, 1,10-phenanthroline, piperazine and liquid ammonia. The complexes were designed with a view to assess their potential anticancer, antioxidant and antibacterial activity. The absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the chosen ligands were calculated by admetSAR software. Metabolic sites of different ligands likely to undergo metabolism were predicted using Metaprint 2D. The proposed complexes were also evaluated for their drug-like quality based on Lipinski's, Veber, Ghose and leadlikeness filters. Druglikeness and toxicity potential were predicted by OSIRIS property explorer. The pharmacokinetic properties and bioactivity scores were calculated by Molinspiration tool. Bioactivity scores of the complexes were predicted ...

Journal of ethnopharmacology, Jan 22, 2018

India being a multicultural nation, every region of the country offers a distinct culinary flavor... more India being a multicultural nation, every region of the country offers a distinct culinary flavor and taste. These flavors are attributed to spices and condiments which form the mainstay of Indian cuisine. Most of these spices and condiments are derived from various biodiversity hotspots in India and form the crux of India's multidiverse and multicultural cuisine. Apart from their varying aromas, flavors and tastes, these spices and condiments are known to possess several medicinal properties also. Most of these spices find considerable mention in Ayurveda, the indigenous system of medicine, as panaceas for several aliments. Cinnamomum zeylanicum (CZ), belonging to family Lauraceae and commonly known as cinnamon is one such spice known to have diverse medicinal properties since time immemorial. In the present study, apoptotic and anti-microbial activity of ethanolic extract of CZ was evaluated against human breast cancer cell line MDA-MB-231 and compared for its effect on normal...

Journal of chemical biology, 2017

2-Butanone thiosemicarbazone ligand was prepared by condensation reaction between thiosemicarbazi... more 2-Butanone thiosemicarbazone ligand was prepared by condensation reaction between thiosemicarbazide and butanone. The ligand was characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry and UV spectroscopic studies. Docking studies were performed to study inhibitory action against topoisomerase II (Topo II) and ribonucleoside diphosphate reductase (RR) enzymes. Inhibition constants (Ki ) of the ligand were 437.87 and 327.4 μM for the two enzymes, respectively. The ligand was tested for its potential anticancer activity against two cancer cell lines MDA-MB-231 and A549 using MTT assay and was found to exhibit good activity at higher doses with an IC50 = 80 μM against human breast cancer cell line MDA-MB-231. On the other hand, no significant activity was obtained against the lung carcinoma cell line A549. Antibacterial activity of the ligand was tested against Staphylococcus aureus and E. coli using the disc diffusion method. Ligand did not exhibit any significant antibacterial...

Journal of Ayurveda and integrative medicine, Jan 6, 2017

The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian tradi... more The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian traditional system of medicine. Withania somnifera Dunal and Withania coagulans Dunal have been documented in folklore as panaceas for various ailments since time immemorial. W. coagulans (WC), commonly called as Indian cheese maker is used for fermenting milk for cheese production in various parts of India. In the study, in vitro cytotoxicity of methanolic extract of dried fruits (berries) of WC was evaluated in a dose dependent manner using trypan blue dye exclusion method against human breast cancer cell line MDA-MB-231 and normal kidney epithelial cell line Vero in the range 20-200 μg/ml. The percentage viability of the cell lines was determined by using MTT assay and cytometry. Methanolic extract of WC showed significant anticancer activity against MDA-MB-231 cell line. Cell viability was reduced to about 50% at 40 μg/ml of methanolic extract in 50% DMSO. Cytotoxicity of the extract was ...

Integrative medicine research, 2017

Aromatherapy is used in clinical settings for patients suffering from several chronic and critica... more Aromatherapy is used in clinical settings for patients suffering from several chronic and critical diseases such as cancer. Ethyl acetate (EA) is a colorless liquid with a characteristic fruity smell and is naturally present in fruits and wines. In the present study, the effect of the aroma of EA was evaluated on human breast cancer cell line MDA-MB-231 and normal cell line, Vero. Cell line viability and mechanism of EA cytotoxicity were determined by Trypan blue dye exclusion assay and phase contrast microscopy. It was found that EA at a concentration of 0.026 M was effective in causing considerable cytotoxicity in breast cancer cells (without even coming in contact with the culture medium and cells), while showing no effect on normal cells. Mechanism of action of EA on cancer and Vero cells was investigated by DNA fragmentation and dye binding assays using agarose gel electrophoresis (AGE) and fluorescence microscopy/cytometry, respectively. It was found that EA aroma induced pred...