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

Abstract

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 (IC 50 ) values of 13.12, 15.34, and 16.34 μM, respectively. Compounds 6 a, 6 d and 6 j exhibited potential anticancer activity against HBT-55 cell line with IC 50 value 17.28, 16.48, and 15.12 μM respectively, when compared to standard drug doxorubicin. Further, docking studies are performed to under-stand 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.

Triazole derivatives as potential xanthine oxidase inhibitors: Design, enzyme inhibition potential, and docking studies

“…Figure 10 represents commercial drugs carrying 1,2,4-triazole moiety as antifungal, [82] antitumor, [83] estrogen blockers, [84] antidepressant, [85] antihypertensives, [86] herbicides, [87] anticonvulsants, [88] antihypnotics, [89] and plant growth regulators. [90] Kantar et al have reported the preparation and evaluation of novel phthalonitrile and zinc(II) phthalocyanines containing morpholino substituted 1,2,4-triazole-3-one derivatives under microwave irradiation as XO inhibitors, as seen in Figure 11.…”

1,2,3-Triazole Scaffold in Recent Medicinal Applications: Synthesis and Anticancer Potentials

“…69 Besides the 1,2,3-triazole ring, some possible targets of the 1,2,4-triazole compounds were reported such as anti-apoptotic Bcl-2 protein, 77 vascular endothelial growth factor 2 (VEGF2), 78 as well as fibroblast growth factor receptor 1 (FGFR1) and Ser-/Thr-specific kinase Akt protein (Akt). 79 Additionally, the nitrogen atom of the 1,2,4-triazole ring was noted to form coordination interaction with the heme Fe ion of the aromatase enzyme contributing to the aromatase inhibitory effect. 80…”

Novel Dioxolane Ring Compounds for the Management of Phytopathogen Diseases as Ergosterol Biosynthesis Inhibitors: Synthesis, Biological Activities, and Molecular Docking

“…13,14 After some triazole fungicides are used, plants cannot synthesize auxin and gibberellin (GA), thereby inhibiting plant growth. 15 On the other hand, 1,2,4-triazole derivatives represent attractive agents for synthetic optimization studies with a wide range of biological activities such as herbicidal, 16 antiproliferative, 17,18 antimicrobial, 19,20 anticancer, 21 analgesic, 22 antioxidant, 23,24 antimalarial, 25 and anticoronavirus activities. 26 Triazole fungicides are sterol biosynthesis C-14 demethylase inhibitors (DMI), 27 which have an inhibitory effect on ergosterol biosynthesis in plants and fungi.…”

“…Triazole fungicides have high activity, broad spectrum, strong systemic conductivity, and adequate half-lives. , Most triazole fungicides can prevent diseases , and regulate plant growth. , After some triazole fungicides are used, plants cannot synthesize auxin and gibberellin (GA), thereby inhibiting plant growth . On the other hand, 1,2,4-triazole derivatives represent attractive agents for synthetic optimization studies with a wide range of biological activities such as herbicidal, antiproliferative, , antimicrobial, , anticancer, analgesic, antioxidant, , antimalarial, and anticoronavirus activities …”