Design and Evaluation of 5-oxo-1,2,4-triazole-3-carboxamide Compounds as Promising Anticancer Agents: Synthesis, Characterization, Cytotoxicity and Molecular Docking Studies.

BACKGROUND

Cancer presents a significant global health challenge, necessitating effective treatment strategies. While chemotherapy is widely employed, its non-specific nature can induce adverse effects on normal cells, prompting the exploration of targeted therapies. The 1,2,4-triazole scaffold has emerged as a promising element in anticancer drug development due to its structural diversity and potential to target cancer cells.

OBJECTIVE

This study aims to synthesize and evaluate novel derivatives derived from the 1,2,4-triazole scaffold for their potential as anticancer agents. Molecular docking techniques are employed to investigate the interactions between the designed derivatives and specific cancer-related targets, providing insights into potential underlying mechanisms.

METHODS

The synthesis involves a three-step process to produce 5-oxo-1,2,4-triazole-3-carboxamide derivatives. Various analytical techniques, including NMR and HRMS, validate the successful synthesis. Molecular docking studies utilize X-ray crystal structures of EGFR and CDK-4 obtained from the Protein Data Bank, employing the Schrödinger suite for ligand preparation and Glide's extra-precision docking modes for scoring.

RESULTS

The synthesis yields compounds with moderate to good yields, supported by detailed characterization. Molecular docking scores for the derivatives against EGFR and CDK-4 revealed diverse affinities influenced by distinct substituents. Compounds with hydroxyl, and halogen, substitutions exhibited notable binding affinities, while alkyl and amino substitutions showed varying effects. The 1,2,4-triazole derivatives demonstrated potential for targeted cancer therapy.

CONCLUSION

The study highlights the successful synthesis of 5-oxo-1,2,4-triazole-3-carboxamides and their diverse interactions with cancer-related targets. The findings emphasized the potential of these derivatives as candidates for further development as anticancer agents, offering insights into structure-activity relationships. The 1,2,4-triazole scaffold stands out as a promising platform for advancing cancer treatment with enhanced precision and efficacy.