Synthesis and synergistic studies of isatin based mixed ligand complexes as potential antifungal therapeutic agents

Ovas Ahmad Dar; Shabir Ahmad Lone; Manzoor Ahmad Malik; Faisal Mohammed Aqlan; Mohmmad Younus Wani; Athar Adil Hashmi; Aijaz Ahmad

doi:10.1016/j.heliyon.2019.e02055

Synthesis and synergistic studies of isatin based mixed ligand complexes as potential antifungal therapeutic agents

Heliyon. 2019 Jul 17;5(7):e02055. doi: 10.1016/j.heliyon.2019.e02055. eCollection 2019 Jul.

Authors

Ovas Ahmad Dar¹, Shabir Ahmad Lone², Manzoor Ahmad Malik¹, Faisal Mohammed Aqlan³, Mohmmad Younus Wani³, Athar Adil Hashmi¹, Aijaz Ahmad^{2

4}

Affiliations

¹ Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India.
² Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
³ Chemistry Department, Faculty of Science, University of Jeddah, P.O. Box 80327, Jeddah 21589, Kingdom of Saudi Arabia.
⁴ Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, 2193, South Africa.

Abstract

Metal based drugs are important class of chemotherapeutic agents that have the potential to circumvent drug resistance. Increasing drug resistance, treatment failures and limited treatment options necessitates the development of new therapeutic drugs with different mechanisms of action. Towards this direction, we synthesized a series of isatin based mixed ligand complexes of [Cu(dbm)LClH₂O] (mlc1), [Co(dbm)LCl₂]^‒ (mlc2) and [Ni(dbm)LClH₂O] (mlc3) and evaluated their antifungal activity alone and in combination with fluconazole (FLC) against seven different Candida albicans isolates. The insight mechanism of antifungal action was revealed by studying apoptosis via terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The study revealed that all these compounds showed antifungal activity at varying concentrations with mlc3 as the most potent compound with minimum inhibitory concentration ranging from 0.5-8 μg/mL and minimum fungicidal concentration ranging from 4-16 μg/mL. Upon combination with FLC, most of the interactions were either synergistic (54 %) or additive (32 %) with no antagonistic combination against any of the tested isolate. The study on their mechanism of action revealed that these compounds show apoptotic effect on C. albicans at sub-inhibitory concentrations, suggesting that strategies to target this process may augment the current antifungal treatment modalities.

Keywords: Inorganic chemistry; Microbiology; Organic chemistry; Pharmaceutical chemistry; Pharmaceutical science.