Green Synthesis, Biological Evaluation, and Molecular Docking of 4'-(Substituted Phenyl)Spiro[Indoline-3,3'-[1,2,4]Triazolidine]-2,5'-Diones

Abstract

We reported herein a green and efficient catalyst-free synthesis of 4'-(substituted phenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-diones (3a–g) in excellent yields. A one-pot multi-component synthesis was achieved using a glycerol-water (4:1) green solvent system. The current synthetic procedure has the advantage of being environmentally friendly, catalyst free, and having a simple workup with high yields. The structure of the title compounds (3a–g) was confirmed by infrared (IR), nuclear magnetic resonance (NMR) and mass spectral data, followed by their biological evaluation. Using the standard protocol, all of the compounds were tested for antibacterial, antifungal, and antitubercular activities. 4'-(4-Chlorophenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-dione (3b) was found to be the most potent compound in the series, with MIC values ranging from 12.71 to 50.84 M, but it was found to be inactive against Mycobacterium tuberculosis H₃₇Ra and M. bovis. 4'-(4-Methoxyphenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-dione (3e) displayed significant antifungal activity with MIC values of 12.89 and 25.78 µM. The SwissADME prediction studies of revealed that the compounds (3a–g) followed the Lipinski rule of 5 and have good absorption from gastrointestinal tract. The title compounds were also investigated using molecular docking against bacterial DNA gyrase (PDB ID: 1KZN).

Graphical Abstract

Keywords:

• Spiro-fused indinones
• green synthesis
• antibacterial
• antifungal
• antitubercular
• molecular docking
• DNA gyrase

Disclosure statement

No potential conflict of interest was reported by the author(s).

Acknowledgement

The current research is supported by Taif University Researchers Supporting Project number (TURSP-2020/293), Taif University, Taif, Saudi Arabia.