Synthesis, Anticancer Activity and Computational Docking Techniques of Some Novel Derivatives Based on Indole Bearing Oxadiazole–Triazole Moieties
Gopalarao Gogisetti, Tejeswara Rao Allaka, Umamaheswararao Kanna, Sravanthi Basireddy, Ravi Kumar Ganta, Vishal Sharma, Bhaskara Rao Tadiboina
Abstract
Abstract In this study, a new series of 1,4-disubstituted-1,2,3-triazole and 2,5-disubstituted oxadiazole tethered indole compounds were synthesized and their molecular structures were characterized by using 1H NMR, 13C NMR, FT–IR, mass and elemental analysis techniques. In particular 3-chloro-5-fluorophenyl-1,2,3-triazolylacetamide-1,3,4-oxadiazole, 2,6-difluorophenyl-triazolyloxadiazole, 4-trifluoromethylphenyl-triazolyloxadiazole had IC50 range 3.2–3.8 μg/mL against MCF-7 whereas 2,6-difluorophenyl-1,2,3-triazole-1,3,4-oxadiazole linked indole, 4-trifluoromethylphenyl-triazolyloxadiazole, 2-nitrophenyl-1,2,3-triazolyl-1,3,4-oxadiazole, 2,5-dimethoxyphenyl-1,2,3-triazolyl-1,3,4-oxadiazole and 3-chloro-5-fluorophenyl-triazolyloxadiazole, 3-chloro-5-fluorophenyl-1,2,3-triazolylacetamide-1,3,4-oxadiazole are active against MDA-MB-468 cell line with IC50 3.2–8.1 μg/mL respectively. Notably 3-chloro-5-fluorophenyl-1,2,3-triazolylacetamide-1,3,4-oxadiazole, 4-trifluoromethylphenyl-triazolyloxadiazole exhibited highest amino acid bonding interactions like AspA:124, ArgA:189, AspA:173, AsnA:69, LysA:168 (2), SerA:171, ArgA:75, Ala:44, LysA:52, GluA:72, TyrA:193, ThrA:48, LysA:47, GluA:72, ArgA:74. Final scaffolds p-tolyl-1,2,3-triazolyl-1,3,4-oxadiazole, 2,6-difluorophenyl-1,2,3-triazole-1,3,4-oxadiazole, 4-fluorobenzyl-1,2,3-triazolyl-1,3,4-oxadiazole, and 3,5-dichlorophenyl-1,2,3-triazolyl-1,3,4-oxadiazoles acquiring highest potency drug-likeness properties and processing Lipinski’s rule of five as good oral bioavailability agents.