Microwave-assisted synthesis, antimicrobial, antiquorum-sensing and cytotoxic activities of a new series of isatin-β-thiocarbohydrazones

Abstract

New isatin-β-thiocarbohydrazone hybrids 4-17 were designed relied on isatin scaffold to generate various analogs with expected antimicrobial activity. The new hybrids were estimated for antibacterial effectiveness over S. aureus, B. cereus and E. coli, and antifungal efficacy over C. albicans and A. fumigatus. Compound 14 evinced the highest efficacy over A. fumigatus and C. albicans. In addition, 5 and 12 showed eminent efficacy toward A. fumigatus, where compounds 4, 7, 9, 11, 13, 15 and 16 exhibited moderate activity over the same fungus. Moreover, 6 and 9 displayed moderate activity over C. albicans. The new compounds were also estimated for antiquorum-sensing effectiveness against C. violacium, where compound 17 showed interesting activity. In vitro cytotoxicity assay of the new analogs was done over Hela and COS-7 cancer cell lines. All analogs have IC₅₀ values >50 μM toward both cell lines.

Graphical Abstract

Compound 14 demonstrated the highest efficacy over A. fumigatus (MIC = 39.06 µg/mL). Also, it displayed acceptable antiquorum-sensing activity, and it was proven to be an excellent candidate for evolution of new more efficient antifungal analogs.

Keywords:

• Isatin
• antimicrobial
• antiquorum-sensing
• cytotoxicity

Acknowledgements

Gratitude to Georgia State University, USA, for implementing spectral analysis.

Supporting Information

Results of in silico studies, detailed experimental procedures, ¹H, ¹³C-NMR and HRMS spectra are presented in the supplemental data.