Synthesis and biological evaluation of heterocyclic 1,2,4-Triazole scaffolds as promising pharmacological agents

Abstract

Background: Triazole is an important heterocyclic moiety that occupied a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, antiurease , anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic, antimigrain agents.Methods: The structure of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU and cisplatin as standards.Results, discussion and conclusion: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1µM, MICAmo = 17.1µM) and fluconazole (MICFlu = 20.4µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity showed by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT 116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).