Abstract

Spiro-compounds are a significant class of naturally occurring materials distinguished by their prominent biological characteristics. Spiro[indole-thiazolidines] analogues find an extensive application in the development of biologically active compounds. The synthesis of the 4′-(substitutedphenyl)spiro[indoline-3,3′-[1,2,4]triazolidine]-2,5′-diones (3a-d) described here was quick and efficient, and it produced excellent yields. The synthesis was carried out in a hydro-alcoholic (EtOH:H2O; 1:2 v/v) system with an addition of 30% mol of boric acid in glycerol. The structure of the prepared compounds was validated using infrared (IR), nuclear magnetic resonance (1H & 13C NMR) and mass spectral (GC-MS) data, followed by their antibacterial, antitubercular and antifungal activities. Among the series, 4́-(3-chloro-4-fluorophenyl)spiro[indoline-3,3́-[1,2,4]triazolidine]-2,5́-dione (3d) was found to be the most potent, with minimum inhibitory concentrations (MICs) values ranging from 4 to 8 µg/mL against both the gram positive (Bacillus subtilis and Staphylococcus aureus) as well as gram negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. However, the compound 3d was found to have inconsequential activity against the mycobacterium strains (Mycobacterium tuberculosis H37Ra and M. bovis) and less activity against fungal strains (Aspergillus niger and Candida albicans). On the other hand 4́-(2-methoxyphenyl)spiro[indoline-3,3́-[1,2,4]triazolidine]-2,5́-dione (3c) displayed moderate but significant antifungal activity. The title compounds (3a-d) were further subjected to ADME and toxicity prediction as well as in-silico molecular docking studies against bacterial DNA gyrase (PDB ID: 6KZV). All the compounds (3a-d) followed the Lipinski's rule of five and were predicted as free from toxicities like immunotoxicity, mutagenicity and cytotoxicity and placed in Class IV category (300 < LD50 ≤ 2000). The docking score of the compound 3d was found to be −6.689 kcal/mol and demonstrated H-bond interactions with the residue Arg76 and Asp73 via water molecule.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.