DESIGN, SYNTHESIS, BIOLOGICAL EVALUATION, AND COMPUTATIONAL INSIGHTS OF 1,2,4-TRIAZOLE-BASED SCHIFF AND MANNICH BASE DERIVATIVES INCORPORATING 3,4,5-TRIHYDROXYBENZOIC ACID
DOI:
https://doi.org/10.3126/jist.v31i1.85935Keywords:
1,2,4-Triazole, Antimicrobial activity, Computational studies, Mannich base, Schiff baseAbstract
1,2,4-Triazole is a privileged heterocyclic scaffold with various biological activities and extensive pharmaceutical applications. In this work, a series of new Schiff base (5a and 5b) and Mannich base (6a and 6b) derivatives of 1,2,4-triazole incorporating 3,4,5-trihydroxybenzoic acid were synthesized via a multi-step synthetic route. Thin Layer Chromatography (TLC), melting point analysis, UV-Vis, FT-IR, 1H-NMR, and 13C-NMR spectroscopy were utilized to verify their molecular framework. The existence of mixture of E and Z geometric isomers determined by NMR spectral analysis indicated the presence of stereoisomeric diversity in the target compounds. These newly produced compounds were tested concerning their in vitro antimicrobial, antioxidant and cytotoxic properties. The Mannich base derivatives (6a and 6b) demonstrated enhanced antimicrobial activity, exhibiting inhibition zones of up to 31 mm against Bacillus subtilis and 33 mm against Saccharomyces cerevisiae, surpassing the corresponding Schiff bases and showing responses comparable to ciprofloxacin and itraconazole under the tested conditions. In the DPPH assay, compounds 6a and 5a displayed notable radical scavenging activity (IC50 = 2.350 and 2.962 mg/mL, respectively), although lower than standard ascorbic acid. Brine shrimp lethality assay indicated concentration-dependent cytotoxicity, with LC50 values ranging from 48.39 to 157.90 µg/mL. Quantum chemical calculations (DFT-based geometry optimization, HOMO-LUMO analysis, and molecular electrostatic potential mapping) provided insights into electronic properties and reactive sites. Moreover, ADMET predictions suggested favorable pharmacokinetic profiles and low toxicity risks for most of these synthesized compounds. The present study highlights these triazole-based derivatives as promising candidates for further development in the field of medicinal chemistry.
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