5-Fluoro-1H-indole-2,3-dione-triazoles- synthesis, biological activity, molecular docking, and DFT study

Abstract

An environmental friendly heterogeneous catalyst Cell-CuI-NPs was employed for the synthesis of biologically promising 1-((1-aryl)-1H-1,2,3-triazol-4-yl)methyl-5-fluoroindoline-2,3-diones via CuAAC click reaction of 5-fluoro-(1-prop-2-ynyl)indoline-2,3-dione, an alkyne with various organic azides in aqueous medium. Compounds 4b, and 4c, with MIC values 0.0075, 0.0075, 0.0082, 0.0164 μmol/mL for S. Epidermidis and B. Subtilis, respectively and compound 7b with MIC value 0.0156 for each S. Epidermidis, E. Coli, &P. Aeruginosa bacterial strains exhibited considerable antibacterial potency with the reference drug Ciprofloxacin (MIC: 0.0047 μmol/mL). On antifungal activity investigation, compound 4a, 4d, and 7c (MIC: 0.0075, 0.0082, and 0.0092 μmol/mL, respectively) for A. Niger exhibited better potency than reference drug Fluconazole (MIC: 0.0102 μmol/mL). Also, compound 4a, 4d, and 4e (MIC: 0.0075, 0.0082, and 0.0090 μmol/mL, respectively) for C. Albicans demonstrated considerable potency with respect to reference antifungal drug Fluconazole (MIC: 0.0051 μmol/mL). Antibacterial and antifungal activity results showed that incorporation of triazole unit in an alkyne 2 improved the potency. Molinspiration physicochemical parameters revealed that all the synthesized 5-fluoroisatin-triazole molecules 4a-e and 7a-e have possessed good drug like properties. Further, antimicrobial activity results were supported by the molecular docking on alkyne 2 and its active triazole 4a as well as DFT study by B3PW91 level with 6-311G(d,p) basis set. The FMOs also revealed that incorporation of triazole moiety on to alkyne 2 has improved the pharmacological activities of the resulted triazoles 4a-e and 7a-e.