S-benzyldithiocarbazate imine coordinated metal complexes kill Candida albicans by causing cellular apoptosis and necrosis

• Published in: Bioorganic chemistry 2020-05, Vol.98, p.103771, Article 103771
• Main Authors: Malik, Manzoor Ahmad, Lone, Shabir Ahmad, Wani, Mohmmad Younus, Talukdar, Md. Ikbal Ahmed, Dar, Ovas Ahmad, Ahmad, Aijaz, Hashmi, Athar Adil
• Format: Article
• Language: English
• Subjects: Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Candida albicans; Candida albicans - drug effects; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Dithiocarbazate; Dose-Response Relationship, Drug; Hydrazines - chemistry; Hydrazines - pharmacology; Imines - chemistry; Imines - pharmacology; Metal complexes; Microbial Sensitivity Tests; Molecular Structure; Necrosis; Structure-Activity Relationship
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.103771

S-benzyldithiocarbazate imine coordinated metal complexes showed excellent anti-Candida activity by causing cellular apoptosis and necrosis. [Display omitted] •S-benzyldithiocarbazate imine coordinated homoleptic transition metal complexes were synthesized.•Metal complexes were evaluated for their anti-Candida activity and membrane disruption potential.•Ni complex (dtc3) was found to be highly active with minimum inhibitory concentration (MIC) values ranging from 1 to 32 µg/mL.•These complexes kill Candida albicans by inducing cellular apoptosis and necrosis. Development of new chemotherapeutic agents and strategies are urgently needed to curb and halt the growing menace caused by hard-to-treat microbes. Coordination of metals to bioactive organic ligands is now considered to be an efficient strategy for delivering bioactive compounds inside the microbial cell membranes. Metal complexes have been effectively used to treat many dreadful diseases were other treatment modalities had failed. Use of metal complexes to treat microbial infections is now conceived to be an alternative and efficient strategy. Towards this, some new homoleptic transition metal complexes, obtained by coordination of metal ions to bioactive S-benzyldithiocarbazate Schiff-base ligands were evaluated for their anti-Candida activity and their potential to disrupt the membrane architecture. The complexes displayed remarkable antifungal activity against a wide spectrum of fluconazole susceptible and resistant Candida albicans isolates, with Ni complex (dtc3) being highly active with minimum inhibitory concentration (MIC) values ranging from 1 to 32 µg/mL. Cell viability assay confirmed the fungicidal activity of these metal complexes, especially the complex dtc3. These metal complexes kill Candida albicans by inducing cellular apoptosis and necrosis thereby causing phosphatidylserine externalization as revealed by Annexin V-FITC and propidium iodide staining assays.