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

Abstract 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 ( 1 H & 13 C), FT–IR and mass spectrometry. Among the tested compounds, hybrids 5 b , 5 g exhibited exceptional anticancer susceptibilities with IC 50 =8.8±0.9, 9.2±1.5 μM 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 μM, whereas 5 d , and 5 g showed potent anticancer activity against colorectal cancer cell line HT29 with IC 50 values 7.1±±0.9, 7.7±1.2 μM 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.