Synthesis, Anticancer Activity and Computational Docking Techniques of Some Novel Derivatives Based on Indole Bearing Oxadiazole–Triazole Moieties

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.