gowramma byran - Academia.edu (original) (raw)

Papers by gowramma byran

Indian Journal of Pharmaceutical Education and Research, 2017

Introduction: In general, 9-aminoacridine derivatives are inhibiting DNA topoisomerase II (topoII... more Introduction: In general, 9-aminoacridine derivatives are inhibiting DNA topoisomerase II (topoII) because of their strong activity due to the ability of acridine nucleus to intercalate into DNA base pair. To get insight of the intermolecular interactions, the molecular docking studies are performed at active site of topoisomerase II. Aim: In this study, an attempt is made for identification of potential ligands from oxazine substituted 9-anilino acridines targeted against topoisomerase-II (1ZXM) using molecular modelling and docking studies by using Schrodinger suit-2012 Maestro 9.3 version. Insilco ADMET screening also performed by qikprop module of Schrodinger suit. Results: The relative binding affinity of the designed compounds towards topoisomerase-II (1ZXM) was selected on the basis of docking score, GLIDE score and interaction patterns. Several compounds showed strong hydrogen bonding interactions with amino acid residues and their hydrophobic interactions and other parameters could also explain their potency to inhibit topoisomerase-II (1ZXM). The oxazine substituted 9-anilino acridine derivatives 1a-1k have good binding affinity with Glide score in the range of-5.7 to-8.06 when compared with the standard ledacrine (-5.24). The ADMET screening of the designed compounds have almost all the properties of the compounds are within the recommended values. Conclusion: Hence, this study provides evidence for consideration of valuable ligands in oxazine substituted 9-anilino acridine derivatives as potential topoisomerase-II inhibitor and further in vitro and in vivo investigations may prove its therapeutic potential

Asian Journal of Pharmaceutical and Clinical Research, 2019

Objective: In the present study, an isocratic chiral reverse-phase high-performance liquid chroma... more Objective: In the present study, an isocratic chiral reverse-phase high-performance liquid chromatography method was developed and the resolution of the drug and complete separation from its degradation products were successfully achieved. Methods: An isocratic method developed with a Phenomenex Lux 5 μ Cellulose 1 (150 mm×4.6 mm i.d., 5 μ) using UV detector at wavelength of 220 nm, with a mobile phase consisting of methanol:0.1% diethylamine (60:40% v/v) and a flow rate of 1 ml/min. The drug was subjected to alkaline, acidic, neutral, oxidative, and photolytic to apply stress conditions. The stressed samples were analyzed by the proposed method. Results: The described method was linear over the range of 3–7 μg/ml for R-enantiomer and 9–21 μg/ml of S-enantiomer, respectively. The limit of detection and limit of quantification of R and S enantiomers were found to be 0.56 μg/ml and 0.18 μg/ml, respectively. Conclusion: The method provides good sensitivity and excellent precision and r...

Journal of the Iranian Chemical Society, 2020

γ-Secretase inhibitors (GSIs) are repurposed as cancer therapeutics based on the promising inhibi... more γ-Secretase inhibitors (GSIs) are repurposed as cancer therapeutics based on the promising inhibition of NOTCH1 signalling pathway in various cancers. GSIs are a class of small-molecule compounds that target the Notch pathway and have been tested to treat various types of cancers in preclinical and clinical trials. Although GSIs elicit a response in some tumours as single agents and sensitize to cytotoxic and targeted therapies, they have not yet been approved for cancer therapy. A new series of chroman-4-one fused 1,3,4-thiadiazole derivatives has been synthesized with the help of different aromatic benzaldehydes, and the final compounds were characterized by FT-IR and 1 HNMR. Chroman-4-one fused 1,3,4-thiadiazole derivatives were synthesized by the reaction of Schiff base derivatives with chroman-4-one fused 1,3,4-thiadiazole. All the synthesized compounds were screened for their anticancer activity. These compounds were evaluated for their anticancer activity against MDA-MB-231, MCF-7, and Vero cancer cell lines. Four of the compounds possessed good to moderate anticancer activity. Four of the synthesized compounds, i.e. 3a, 3c, 3i, and 3e, were found to possess maximum growth inhibition. In conclusion, the designed chromanone-1,3,4-thiadiazole scaffold is an interesting anticancer pharmacophore and considered as novel lead scaffold for any future optimization.

Annals of Medicine & Surgery

https://oversea.onlinecnki.net/details.php?id=DOI:10.17605/OSF.IO/CHKNW

Applied Biochemistry and Biotechnology, Oct 20, 2022

CERN European Organization for Nuclear Research - Zenodo, Jun 29, 2022

Current Enzyme Inhibition

: Poly [ADP-ribose] polymerase-1 [PARP-1] is a chromatin-bound nuclear enzyme that gets activated... more : Poly [ADP-ribose] polymerase-1 [PARP-1] is a chromatin-bound nuclear enzyme that gets activated by DNA damage. It facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Increased PARP-1 expression is observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. PARP-1 interacts directly and indirectly with various oncogenic proteins and regulates several transcription factors, thereby modulating carcinogenesis. There is a lot of pre-clinical and clinical data supporting the use of PARP-1 inhibitors [PARP-1i] in cancers that express homologous recombination deficiencies like mutations within the BRCA-1/2 genes. Therapeutic inhibition of PARP-1 is therefore perceived as a promising anticancer strategy, and numerous PARP-1i are currently under development and clinical evaluation. Currently, there are 4 FDA-approved PARP-1i products on the market, and a few more are in the last stage of clinical development. All the molecules are non-selective PARP-1i. While giving promising results, PARP-1i have their own disadvantages, like safety problems, resistance, etc. Looking at the success rate of PARP-1i in various solid tumours, there is a need for novel and selective PARP-1i. In this review, we discuss various aspects related to PARP-1i, like recent developments, overcoming resistance, and selectivity criteria of new molecules for potential PARP-1i.

Annals of Medicine and Surgery

RASAYAN Journal of Chemistry

Thiadiazole is a heterocyclic molecule made up of one sulphur atom, two nitrogen atoms, and two d... more Thiadiazole is a heterocyclic molecule made up of one sulphur atom, two nitrogen atoms, and two double-bonded 5- membered ring systems. Heterocyclic compounds having biological activity serve a significant role in medicinal chemistry. More than one or two heteroatoms are also included in the five-membered ring, including thiadiazole, oxazole, thiazole, azole, pyrrole, triazine, and others. Thiadiazole has been shown to have anticancer, antiinflammatory, anti-diabetic, antimicrobial, antifungal, antibacterial, antiviral, anti-tuberculosis, anticonvulsant, antidepressant, antileishmanial, and other biological effects.

Mini-Reviews in Medicinal Chemistry

: Acridine derivatives have been thoroughly investigated and discovered to have multitarget quali... more : Acridine derivatives have been thoroughly investigated and discovered to have multitarget qualities, inhibiting topoisomerase enzymes that regulate topological changes in DNA and interfering with DNA's vital biological function. This article discusses current progress in the realm of novel 9-substituted acridine heterocyclic compounds, including the structure and structure– activity connection of the most promising molecules. The IC50 values of the new compounds against several human cancer cell lines will also be presented in the publication. The review also looks into the inhibition of topoisomerase by polycyclic aromatic compounds. Background: Acridine rings can be found in molecules used in many different areas, including industry and medicine. Nowadays, acridines with anti-bacterial activity are of research interest due to decreasing bacterial resistance. Some acridine derivatives showed antimalarial or antiviral activity. Acridine derivatives were also investigated for anti-tumor activity due to the interaction with topoisomerase II and DNA base pairs. Considering these possible uses of acridine derivatives, this work overviewed all significant structure performances for the specific action of these compounds. Objective: The objective of this study is to review the activity of acridines as anti-proliferative agents. Design: This review is designed as acridines acting as topoisomerase I and II inhibitors/ poison, Acridines on the G-quadraplux interaction, Acridines with metal complexes, Acridines with quinacrine scaffold, Acridines with sulphur moiety. Conclusion: Although introduced in the 19th century, acridine derivatives are still of scientific interest. In this review, acridine derivatives with various biological activities (antiparasitic, antiviral, anti-bacterial, and antiproliferative) and their structure-activity relationship analyses are presented. Although several mechanisms of their action are known, the only important are discussed here. It can be concluded that the dominant mechanisms are DNA intercalation and interaction with enzymes.

Novel poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing, the 4-(benzylideneamino)-<i&g... more Novel poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing, the 4-(benzylideneamino)-N-(quinolin-8-yl)benzamide moiety, were designed and synthesized. The docking study revealed that the designed compounds possess significant to moderate interaction with the targeted enzyme PARP1. Among them compound 3d (−52.04 K/cal) and 3e (−50.234 K/cal) showed similar Glidescore compared to Olaprib (−57.76 K/cal). Some of the synthesized compounds displayed good PARP-1 inhibitory activity, and among them, 3d and 3e were the most potent one. Enzyme inhibitory assay indicated that the compounds 3d, 3e, 3i and 3o exhibited an enzyme inhibitory activity against PARP-1 enzyme similar to that of olaparib. All the synthesized compounds were screened for their in vitro anticancer activity against MCF-7 and MDA-MB-232 cell lines. Among them, compound...

Journal of Biomolecular Structure and Dynamics, 2020

Abstract Coronavirus disease (COVID-19), a life-threatening disease, is caused by SARS-CoV-2. The... more Abstract Coronavirus disease (COVID-19), a life-threatening disease, is caused by SARS-CoV-2. The targeted therapeutics of small molecules helps the scientific community to fight against SARS-CoV-2. In this article, some oxazine substituted 9-anilinoacridines (A1–A48) was designed by docking, MM-GBSA and molecular dynamics (MD) simulation studies for their COVID-19 inhibitory activity. The docking of ligands A1–A48 against SARS-CoV-2 (PDB ID: 5R82) are performed by using Glide module, in silico ADMET screening by QikProp module, binding energy using Prime MM-GB/SA module, MD simulation by Desmond module and atomic charges were derived by Jaguar module of Schrodinger suit 2019-4. Compound A38 has the highest G-score (−7.83) when compared to all the standard compounds which are proposed for COVID-19 treatment such as ritonavir (−7.48), lopinavir (−6.94), nelfinavir (−5.93), hydroxychloroquine (−5.47) and mataquine (−5.37). Compounds A13, A23, A18, A7, A48, A46, A32, A20, A1 and A47 are significantly active against SARS-CoV-2 main protease when compared with hydroxychloroquine and mataquine. The residues GLN19, THR24, THR25, THR26, LEU27, HIE41, SER46, MET49, ASN119, ASN142, HIE164, MET165, ASP187, ARG188 and GLN189 of SARS-CoV-2 main protease play a crucial role in binding with ligands. The in silico ADMET properties of the molecules are within the recommended values. The binding free energy was calculated using PRIME MM-GB/SA studies. From the ligands A38, A13, A23, A18, A7, A48 and A46 with significant Glide scores may produce significant COVID-19 activity for further development. Compound A38 was subjected to MD simulation at 100 ns to study the dynamic behaviour of protein–ligand complex. Communicated by Ramaswamy H. Sarma

Journal of Medicinal Chemistry, 2012

The influenza virus nucleoprotein (NP) is an emerging target for antiinfluenza drug development. ... more The influenza virus nucleoprotein (NP) is an emerging target for antiinfluenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC 50 values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC 50 values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.

Rasayan Journal of Chemistry

Seven protein families known as class III histone deacetylase for their characteristic features h... more Seven protein families known as class III histone deacetylase for their characteristic features have been reported in mammals. Sirtuin3 (SIRT3) has gained considerable attention among the sirtuin members for its role in neurodegenerative disease. A new series of 4-thiazolidinones fused 1, 3, 4-oxadiazole derivatives have been designed in silico by using Schrodinger software. Molecules showing high affinity with the target protein (4JSR) were selected for the synthesis and analytical methods were used to determine the structures. The synthesized compounds III (a-h) were taken for in vitro cytotoxicity studies by MTT assay technique using SHSY5Y neuroblastoma cell lines. The synthesized compounds III (a-h) were taken for in vitro cytotoxicity studies by MTT assay technique using SHSY5Y neuroblastoma cell lines. Gene expression study was then performed on SIRT-3 gene by reverse transcriptase PCR method. Compound III b and III g were effective with IC50 values of 126.70 and 157.42 respe...

Drug Development and Industrial Pharmacy

Abstract An enantiomeric separation of meclizine enantiomers by liquid chromatography with tandem... more Abstract An enantiomeric separation of meclizine enantiomers by liquid chromatography with tandem mass spectrometry LC-MS method was developed and validated for the analysis of Meclizine enantiomers. Enantiomeric resolution of the drug products were successfully achieved on a Phenomenex® lux cellulose 1 C18 (250 mm × 4.6 mm i.d, 5 µm particle size) column with mobile phase consisting of acetonitrile: 5 mM ammonium format pH (5.5) adjusted with formic acid (90:10) (v/v), and a flow rate of 0.4 mL/min. The developed method provided linear responses within the concentration range 1–5 ng/mL, and regression analysis showed a correlation coefficient value (r2) of 0.999. The optimized mobile phase separated (+) Meclizine at 1.58 min and (-) Meclizine at 2.20 min, respectively. The LC/MS method was validated as per ICH guidelines with respect to specificity, precision, linearity and robustness. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 1.0 ng/mL and 5.0 ng/mL respectively. The proposed method is suitable for analysis of meclizine enantiomers in pharmaceutical formulations and quality control analysis.

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Indo American Journal of Pharmaceutical Research, 2015

Article history To develop a rapid, specific, accurate and efficient liquid chromatography-mass s... more Article history To develop a rapid, specific, accurate and efficient liquid chromatography-mass spectrometry method and validate as per ICH guidelines for the simultaneous estimation of quercetin and rutin from Aganosma dichotoma. The chromatographic separation was achieved by using C18 column, 150 x 4.6mm i.d., 5µ Phenomenex, mobile phase containing methanol: 10mM ammonium acetate (80:20 v/v). The flow rate was 0.4 ml/min. The retention time of quercetin and rutin was found to be 4.09 min and 3.31 min respectively. Quercetin and rutin exhibited linear in the range 1-5 ng/ml and 10-50 ng/ml respectively. The method was validated for the parameters like system suitability, specificity, linearity, accuracy, precision, limit of detection and limit of quantification. The proposed method was successfully applied for the simultaneous estimation of both the constituents in Aganosma dichotoma and established a quantitative method for the simultaneous determination of quercetin and rutin fro...

South African Journal of Botany