Synthesis, characterization, and biological activities of two new pyrazole Schiff base derivatives

Abstract

The development of new heterocyclic scaffolds remains a priority in medicinal chemistry due to the rising challenges of microbial resistance and cancer. In this study, we explored the synergistic potential of combing thiophene-substituted pyrazoles with phenolic Schiff bases. We synthesized two novel derivatives, 3a and 3b, via the condensation of 5-Amino-3-(2-thienyl) pyrazole with salicylaldehyde and 5- bromo-2-hydroxybenzaldehyde. These structures were confirmed using FTIR, ¹H and ¹³C -NMR, UV- visible, mass spectroscopy, and elemental analyses. While both compounds were evaluated for their biological activities, compound 3b-the brominated derivative emerged as a multifaceted bioactive lead. Quantitative microdilution assays showed that 3b exhibited broad spectrum antibacterial activity, with MIC of 0.4 mg/mL against S. aureus and 1.2-2.0 mg/mL against gram negative strains of E. coli, P. aeruginosa and K. pneumoniae. where 3a remained inactive. Furthermore, it showed potent antifungal efficacy against clinical isolates of Candida species with MIC of 0.75 mg/mL, a significant improvement over the 2.0 mg/mL observed for 3a. Cytotoxicity assay indicated that 3b effectively inhibited the growth of MCF7, PC3 and MDA231 cancer lines. While both compounds were confirmed non-mutagenic via the Ames test. 3b revealed a tendency for red blood cell (RBC) lysis at concentrations ≥ 0.25 mg/mL. The integration of a bromide substituent in 3b significantly enhances bioactivity compared to 3a, suggesting that halogenation is key to bioactivity. Our findings suggest that compound 3b is a potential candidate base for tackling both drug-resistance infections and human malignancies.