Dharmendra K Yadav
Gachon University, South Korea
Title: Synthesis, biological evaluation and molecular simulation studies of new arylated benzo[h]quinolines
Biography
Biography: Dharmendra K Yadav
Abstract
In this study, we have carried out Gaussian-based 3D-QSAR model against the target COX-2 with good statistical significance (R2training=0.86) and predictability (Q2training=0.66, Q2test=0.84). The 3D-QSAR includes steric, electrostatic, hydrophobic, and hydrogen bond acceptor field indicators, whereas the potential field contributions indicate that the steric and hydrophobic features of the molecules play an important role in governing their biological activity. The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. Among the synthesized compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and on expression of apoptosis related gene was studied. While their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stress-mediated DNA damage. Molecular simulation study was performed to find binding conformations and different bonding behaviors, in order to reveal the possible mechanism of action behind higher accumulation of active benzo[h]quinolines with β-tubulin.
Recent Publications
1. Yadav DK, Kumar S, Saloni, Singh H, Kim MH, Sharma P. Misra S, Khan F (2017) Molecular docking, QSAR and ADMET studies of withanolide analogs against breast cancer. Drug Design, Development and Therapy 11:1859-1870.
2. Yadav DK, Rai R, Kumar N, Singh S, Misra S, Sharma P, Shaw P, Pérez-Sánchez H, Mancera RL, Choi EH, Kim MH, Pratap R (2016). New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage. Scientific reports 6:38128.
3. Yadav DK, Dhawan S, Chauhan A, Qidwai T, Sharma P, Bhakuni RS, Dhawan OP, Khan F (2014). QSAR and docking based semi-synthesis and in vivo evaluation of artemisinin derivatives for antimalarial activity. Current Drug Target 15(8):753-61.
4. Yadav DK, Ahmad I, Shukla A, Khan F, Negi AS, Gupta A (2014). QSAR and docking studies on Chalcone derivatives for anti-tubercular activity against M. tuberculosis H37Rv. Journal of Chemometrics 28: 499-507
5. Yadav DK, Kalani K, Singh AK, Khan F, Srivastava SK, Pant AB (2014). Design, synthesis and in vitro evaluation of 18β-glycyrrhetinic Acid derivatives for anticancer activity against human breast cancer cell line MCF-7. Curr Med Chem 21(9):1160-70.
