Design, Synthesis, Anticancer and Antimicrobial Evaluation and In Silico Study of Indazole – Pyrimidine – 1,2,3-Triazole Hybrids

Cancer and antibiotic resistance offer serious obstacles in drug discovery and design, which could be addressed by the synthesis of novel heterocyclic compounds with diverse combinations. In view of this a library of new molecular hybrids that contain indazole, pyrimidine, and 1,2,3-triazole heterocycles (6a-l) were synthesized and screened for their in vitro anticancer efficacy against MCF-7, PC-3, and HeLa cancer cell lines, with results compared to those of Doxorubicin. Two molecules with 2-chloro (6d) and 4-nitro (6 g) substituents presented potent activity against the PC-3 cell line, with IC50 values of 3.28 ± 0.07 µM and 3.25 ± 0.06 µM, respectively, with reference to Doxorubicin (IC50 = 3.79 ± 0.02 µM). Another molecule with 3-fluoro (6i) substituent displayed substantial action against the MCF-7 cell line, with an IC50 value of 3.26 ± 0.04 µM. The 4-nitro compound (6 g) exhibited the outstanding activity, with an IC50 value of 3.25 ± 0.07 µM against the HeLa cell line. A diverse selection of bacterial and fungal strains were employed to assess the antimicrobial potential of these compounds, and against the strains 6d, 6 g, 6h, 6i, and 6 l exhibited notably robust action. Molecular docking experiments were conducted to further investigate the binding interactions of these derivatives, compound 6 l scored highest binding affinity value of −10.4 kcal/mol.a The predicted pharmacokinetics of the molecules indicate favorable drug-likeness properties.