Bindu B

Electronics

School of Electronics Engineering

Chennai Campus

Manikandan A.

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Bioorganic Chemistry

A family of 12 triazolo-pyridazine-6-yl-substituted piperazines (5a-l) was synthesized and evaluated for their Dipeptidyl peptidase-4 (DPP-4) inhibition potentials in order to develop them as anti-diabetic medications. In the two-step synthesis process, 6-chloro-3-(m-tolyl)-[1,2,4]triazolo[4,3-b]pyridazine was synthesized with one-pot mode using pyridine, 3,6-dichloropyridazine 5-(3-methyl-phenyl)tetrazole in toluene. Conjugating corresponding 2° amines with 6-chloro-3-(m-tolyl)-[1,2,4]triazolo[4,3-b]pyridazine afforded the target triazolo-pyridazine-6-yl-substituted piperazines (5a-l). DPP-4 inhibition potential of these compounds was testified in silico and in nitro along with their insulinotropic activities in 832/13 INS-1 cells. H2O2 radical scavenging assay and MTT assay were conducted to assess the antioxidant and cytotoxicity of these compounds respectively. Molecular docking and ELISA based enzyme inhibition assay results revealed the strong inhibition potential of the target compounds. MTT assay results indicated a maximum dose of 2.5 nM (IC50 1.25 nM) could be used and above this level vital for the cells. Compounds 5a, 5c, 5g and 5i were found with excellent antioxidant and insulinotropic activity up to 99%.

European Journal of Medicinal Chemistry

Synthesis and discovery of triazolo-pyridazine-6-yl-substituted piperazines as effective anti-diabetic drugs; evaluated over dipeptidyl peptidase-4 inhibition mechanism and insulinotropic activities

Piperazine-azole-fluoroquinolone hybrids: Conventional and microwave irradiated synthesis, biological activity screening and molecular docking studies

Developing a new antibacterial drug by using (Z/E)-4-(4-substituted-benzylidene)-2-isoquinoline-1,3(2H,4H)-diones (5a–h) via DNA gyrase inhibition mechanism is the main aim of this study. DNA gyrase inhibition assay was executed to confirm the DNA gyrase inhibition potentials of 5a–h. DNA gyrase inhibitory potentials were further validated through molecular docking. Docking study was also intended to get more insight into the binding mode of 5a–h into the active site of DNA gyrase A. Agar well diffusion method antimicrobial activity on Gram −ve bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), and Gram +ve bacteria (Staphylococcus aureus (MTCC 96) and Streptococcus pyogenes (MTCC 442) was evaluated. Excellent DNA gyrase inhibition was exhibited by the compound 5c, IC 50 0.55±0.12 μM; 5d, IC 50 0.65±0.075 μg/mL; 5e, IC 50 0.45±0.035 μM; 5f, IC 50 0.58±0.025 μM; 5h, IC 50 0.25±0.015 μM while Clorobiocin (standard) showed IC 50 0.5±0.05 μM. Apart from all the in vitro studies, a plausible mechanism of DNA gyrase inhibition was also proposed through the in silico validations that are including molecular docking, predicted SAR, functional group availability, pharmacokinetic, and ADMET properties. These predictions are well supported to confirm the druggability possibility of the most potent compounds among (Z/E)-4-(4-substituted-benzylidene)-2-isoquinoline-1,3(2H,4H) -diones (5a–h). © 2018 Wiley-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

Molecular Informatics

Computational Approaches to Develop Isoquinoline Based Antibiotics through DNA Gyrase Inhibition Mechanisms Unveiled through Antibacterial Evaluation and Molecular Docking

Unveiling novel 2-cyclopropyl-3-ethynyl-4-(4-fluorophenyl)quinolines as GPCR ligands via PI3-kinase/PAR-1 antagonism and platelet aggregation valuations; development of a new class of anticancer drugs with thrombolytic effects

An eco-friendly catalytic system for multicomponent, one-pot synthesis of novel spiro-chromeno indoline-triones and their anti-prostate cancer potentials evaluated via alkaline phosphatase inhibition mechanism

Synthesis and molecular validation of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives (4a-h) as antibacterial/DNA gyrase inhibitors reported. Primarily, 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives were docked into the active sites of DNA gyrase A&B, to ensure the binding mode of the compounds, and the results were superior on DNA gyrase A over DNA gyrase B. Based on this, S. aureus DNA gyrase A assay was proposed and executed. Most prominent DNA gyrase inhibition showed by 6-fluoro-2-(3-phenoxyphenyl)-4-phenylquinoline (4c), IC50 0.389μg/mL; 2-(3-phenoxyphenyl)-4-phenylquinolin-6-ol (4e), IC50 0.328μg/mL; and 5,7-dichloro-2-(3-phenoxyphenyl)-4-phenylquinolin-6-ol (4h), IC50 0.214μg/mL which were substituted with fluorine (4F), nitrile (4CN), hydroxyl group (4OH) and dichloro-hydroxyl (3,5Cl, 4OH) groups in the quinoline scaffold. Antimicrobial activity on Gram-ve bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), and Gram+ve bacteria Staphylococcus aureus (MTCC 96) and Streptococcus pyogenes (MTCC 442) was evaluated. Excellent antibacterial activity showed by S. aureus and S. pyogenes which indicates the activity dominance of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives on Gram+ve bacteria rather than Gram-ve. Subsequently, the cytotoxicity of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives was evaluated. Cytotoxicity results of MCF-7 (human breast cancer) and G361 (skin melanoma cancer) cell lines reveals that the 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives are highly toxic to cancer cells. Predicted SAR, Lipinski's filter, Pharmacokinetic, and ADMET properties were also ensured the druggability probabilities of most favorable compounds among 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives.

Bioorganic & Medicinal Chemistry

Molecular docking, discovery, synthesis, and pharmacological properties of new 6-substituted-2-(3-phenoxyphenyl)-4-phenyl quinoline derivatives; an approach to developing potent DNA gyrase inhibitors/antibacterial agents

Discovery, synthesis and molecular substantiation of N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides as anticancer agents

Journal	Data powered by TypesetBioorganic Chemistry
Publisher	Data powered by TypesetElsevier BV
ISSN	0045-2068
Open Access	0