Synthesis, characterization, and biological activities of some heterocyclic compounds derived from coupling carboxylic acids and 1H-1,2,4-triazole-3,5-diamine
摘要
A coupled reaction between 1H-1,2,4-triazole-3,5-diamine and carboxylic acids was studied to synthesize new amido-1H-1,2,4-triazoles derivatives (1–5), under various optimization conditions, leading to the higher yield of this coupling obtained with N,N′-diisopropylcarbodiimide (DIC) as a catalyst at 0 °C for 48 h. The produced compounds were subsequently identified by analytical techniques (1H NMR, 13C NMR and IR) and evaluated for various biological activities, including antibacterial, anti-inflammatory, and antioxidant effects. The findings demonstrated that all compounds exhibited powerful antibacterial effect against the tested strains, as found by the promising activities with minimum inhibitory concentration (MIC), ranging from 0.07 to 3.24 µmol mL−1 when compared to amoxicillin as a positive control (0.171 ≤ MIC ≤ 0.684 µmol mL−1). Of particular, compound 5 showed the highest antibacterial activity among other compounds. The in vitro investigation was conducted on the synthesized compounds to estimate their anti-inflammatory effects, as assessed by bovine serum albumin denaturation approach. Compounds 4 and 5 showed excellent anti-denaturation activities with IC50 values of 0.11 and 0.10 µmol mL−1, respectively, compared to diclofenac sodium (standard drug) and other compounds (IC50 from 0.19 to 0.27 µmol mL−1). Synthesized compounds were also tested for their antioxidant power, as assessed by DPPH radical-scavenging activity, and the maximum inhibition was found to be 33.17% at 100 µg mL−1. Furthermore, analysis with molecular docking against bacterial enzymes revealed that the compounds 2 and 5 showed a strong interaction with high docking scores of 1RO5 (− 8.160 kcal mol−1) and 2XCT (− 7.994 kcal mol−1) proteins, respectively. Therefore, these compounds can be considered as a promising candidate for antibacterial agents.
Graphical abstract