New 1,2,4-Triazole Scaffolds as Anticancer Agents: Synthesis, Biological Evaluation and Docking Studies

A series of novel 4,5-diphenyloxazol-1,2,4-triazole derivatives (6 a-6 l) were synthesized and screened for anticancer activity against the prostate lung cancer cell lines viz., PC-93 and HBT-55. The outcome of the investigation reveals that compounds 6 a, 6 b and 6 j showed potential anticancer activity against PC-93 cell line with the half maximal inhibitory concentration (IC50) values of 13.12, 15.34, and 16.34 mu M, respectively. Compounds 6 a, 6 d and 6 j exhibited potential anticancer activity against HBT-55 cell line with IC50 value 17.28, 16.48, and 15.12 mu M respectively, when compared to standard drug doxorubicin. Further, docking studies are performed to understand the possible interactions responsible for their potential activity by considering the Fibroblast growth factor receptor 1 (FGFR1) and the Ser-/Thr-specific kinase Akt protein (Akt) as target proteins. The amino acid residues from ALA639 to PRO741 of FGFR1 and from GLU17 to ASP292 of Akt proteins are involved in non-covalent interactions with the ligands 6 a-6 l. The insilico pharmacokinetic properties are predicted for the molecules 6 a-6 l to assess the druggability. The study provides that compounds 6 a, 6 b, 6 d, and 6 j scaffolds serve as promising lead molecules for treating cancer and further structure optimizations.

Automated summary

A series of novel 4,5-diphenyloxazol-1,2,4-triazole derivatives were synthesized and screened for anticancer activity against prostate and lung cancer cell lines. Compounds 6a, 6b, 6d, and 6j showed potential anticancer activity, with promising lead molecules identified for further structure optimizations in cancer treatment.