Synthesis of Benzimidazole Based 1,2,4-Triazole Derivatives as Potential Anticancer Agents: In Silico Techniques

Compounds with a 1,2,4-triazole scaffold serve an essential role in organic synthesis, particularly in the synthesis of bioactive organic compounds; thus, the development of new approaches for modifying this scaffold is a very interesting framework of this study. To contribute to the development of an efficient method for the conversion of anticancer triazoles, a novel series of benzimidazole based 1,2,4-triazoles was designed and synthesized. All the newly synthesized derivatives were characterized by NMR (H-1 &C-13), FT-IR and mass spectrometry. Among the tested compounds, hybrids 5 b, 5 g exhibited exceptional anticancer susceptibilities with IC50=8.8 +/- 0.9, 9.2 +/- 1.5 mu M against the tested HCA-7cancer cell line. Anticancer profiles showed that compounds 5 d, 5 i had better anticancer inhibitory potency against a breast cancer cell line MCF-7with IC(50)values 8.3 +/- 2.1, 10.6 +/- 1.2 mu M, whereas 5 d, and 5 g showed potent anticancer activity against colorectal cancer cell line HT29 with IC50 values 7.1 +/-+/- 0.9, 7.7 +/- 1.2 mu M respectively. From docking results, 5 d demonstrated highly stable binding amino acids LeuA : 2247, GlyA : 2449, SerA : 2409, HisA : 2379, AspA : 2373, LysA : 2318, IleA : 2317, IleA : 2246, IleA : 2412, AlaA : 2410, GlnA : 2452, AsnA : 2245, TyrA : 2243, and HisA : 2448, which play a crucial role enabling optimal ligand binding in a crystal structure tyrosine phosphatase mutated in colorectal cancer (PDB: 1WCH). Furthermore, the physicochemical and absorption, distribution, metabolism, and excretion (ADME) filtration molecular properties, estimation of bioactivity, and toxicity scores of these scaffolds were evaluated.