Synthesis of newly designed fatty acid containing benzimidazole-triazole hybrids from sustainable precursor as potential anticancer agents targeting human breast adenocarcinoma

The current challenges of cancer therapies highlight a demanding need for new anticancer agents. In pursuit of better anticancer agents, a series of newly designed fatty acid-containing benzimidazole-triazole derivatives (8a-8j) was designed, synthesized, and evaluated for anti-breast cancer activity. The amphiphilic properties, capacity to regulate membrane permeability and bioactive nature of fatty acid were utilized as important structural elements in this development to enhance anticancer potential. The desired derivatives 8a-8j were synthesized by using a sequential technique that included an initial cyclization process, followed by targeted substitution, and then a click chemistry approach. Compounds 8a-8j were characterized using FTIR, HRMS, ¹H & ¹³C NMR spectroscopy to confirm their structures and verify successful synthesis. ADMET profiling and molecular docking analysis were employed to assess the drug likeness, toxicity properties and binding interactions, highlighting their potential as effective agents in drug development. Synthesized derivatives 8a-8j were evaluated against MCF-7 cells and non-cancerous RPE-1 cells using the MTT assay. Compound 8a, with an IC<inf>50</inf> of 3.71 ± 1.01 µM and selectivity index (SI) = 12.20, surpassed the potency of the standard drug doxorubicin (DOX), with an IC<inf>50</inf> of 4.43 ± 0.91 µM. These cytotoxicity findings were also validated using colony formation assay. The collective experimental as well as computational results suggest that these derivatives 8a-8j possess potential as anticancer agents, meriting future biological research and structural optimizations.