Quinoline‐1,3‐Oxazole Hybrids: Syntheses, Anticancer Activity and Molecular Docking Studies

• Published in: ChemistrySelect (Weinheim) Vol. 5; no. 3; pp. 1097 - 1102
• Main Authors: Shah, Shailesh R., Katariya, Kanubhai D., Reddy, Dushyanth
• Format: Journal Article
• Language: English
• Published: 23-01-2020
• Subjects: 1,3-Oxazole; Anticancer activity; Hydrazone; Molecular Docking; Quinoline
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201903763

In continuation of the synthesis of potent quinoline based anticancer agents, a series of novel quinoline‐1,3‐oxazole hybrids 15 a‐l were synthesized by the condensation reaction of 2‐aryl‐5‐methyl‐1,3‐oxazole‐4‐carbaldehydes 10 a‐f and 6‐bromo/6‐chloro‐2‐methyl‐quinolin‐4‐yl‐hydrazines 14 a/b in good yield. Out of twelve, ten of the synthesized compounds were selected by the National Cancer Institute, USA for anticancer activity screening against 60 different human cancer cell lines representing nine types of cancer. Nine compounds were displayed outstanding antiproliferative activity with GI50 values ranging from 0.26 to 25.6 μM and LC50 values ranging from 2.96 μM to >100 μM. The mean MG‐MID values of GI50, TGI, and LC50 were compared with the methotrexate and four compounds 15 b, 15 d, 15 e, 15 f emerged with important GI50 <2.0 μM. Among all compounds screened, 15 d displayed the highest potency as a cytotoxic molecule. Moreover, new hybrids were also studied for molecular docking into the active binding site of DNA topoisomerase I (htopoI) to understand the binding mode and favorable interactions of active compounds into binding sites of topoisomerase enzyme.
A series of twelve novel quinoline‐1,3‐oxazole hybrids 15 a–l were synthesized and characterized by various spectroanalytical techniques and studied for their in vitro anticancer activity against NCI's sixty cancer cell line panel at single as well as five dose level. Out of all, nine new hybrids molecules (15 b, 15 c, 15 d, 15 e, 15 f, 15 g, 15 h, 15 i, 15 j) displayed outstanding anticancer activity. Further, molecular docking studies have been performed to understand the interactions of the active molecules with DNA topoisomerase I enzyme.