Synthesis, QSAR modeling, and molecular docking studies of 1,2,3-triazo-le-pyrazole hybrids as significant anti-cancer and anti-microbial agents

Abstract

In this research, the synthesis of 1,2,3-triazoles-based pyrazole carbaldehyde via click reaction of 5-azido-3methyl-1-phenyl-1H-pyrazole-4-carbaldehyde with terminal alkynes catalyzed by Cu(OAc)2 is reported. The antimicrobial and anticancer activities of the synthesized compounds were evaluated against the three pathogenic microorganisms: E. coli, P. aeruginosa, and C. albicans; two cancer cell lines were MCF-7 and OVCAR3. Among the screened compounds, 4i possessed the most potential cytotoxic activity against MCF-7 cell lines with an IC50 of 0.101 f 0.002 mu M; in contrast, 4e showed a dual activity as it was highly potent against the OVCAR3 cell line, where the IC50 = 0.264 f 0.0007 mu M, and high antibacterial activity towards E. coli, MIC = 0.431 f 0.009 mu M. Moreover, high antifungal activity appeared in compound 4j against C. albicans with an MIC of 0.558 f 0.01 mu M. In addition, the performance of the constructed QSAR model was assessed through various statistical metrics. Notably, the coefficients of determination (R2) yielded a remarkable value of 0.99, signifying a high degree of correlation between the predicted and observed values. In addition, the mean absolute error (MAE) was found to be 0.014, further attesting to the robustness and predictive capability of the proposed model. Novel compounds were suggested as possible active inhibitors based on the established link within the suggested QSAR model. Molecular docking studies' ligand-receptor (LR) interactions were used to verify and assess the compounds' correctness.