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Gold(III) Complexes with Aromatic Cyano-Substituted Bisdithiolate Ligands as Potential Anticancer and Antimicrobial Agents
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Gold(III) Complexes with Aromatic Cyano-Substituted Bisdithiolate Ligands as Potential Anticancer and Antimicrobial Agents
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Journal Article
Gold(III) Complexes with Aromatic Cyano-Substituted Bisdithiolate Ligands as Potential Anticancer and Antimicrobial Agents
2025
Overview
Cancer and infectious diseases are major causes of global morbidity and mortality stressing the need to find novel drugs with promising dual anticancer and antimicrobial efficacy. Gold complexes have been studied for the past years due to their anticancer properties, with a few of them displaying antimicrobial properties, which support their pharmacological interest. Within this scope, we investigated six gold bisdithiolate complexes [Au (bdt)2]− (1), [Au (dcbdt)2]− (2), [Au (3-cbdt)2]− (3), [Au (4-cbdt)2]− (4), [Au (pdt)2]− (5) and [Au (dcdmp)2]− (6), and) against the ovarian cancer cell lines A2780 and A2780cisR, the Gram-positive bacteria Staphylococcus aureus Newman, the Gram-negative bacteria Escherichia coli ATCC25922 and Burkholderia contaminans IST408, and the pathogenic yeasts Candida glabrata CBS138 and Candida albicans SC5134. Complexes 2 and 6, with ligands containing aromatic pyrazine or phenyl rings, substituted with two cyanonitrile groups, showed after 24 h of incubation high anticancer activities against A2780 ovarian cancer cells (IC50~5 µM), being also able to overcome cisplatin resistance in A2780cisR cells. Both complexes induced the formation of ROS, activated caspase-3/7, and induced necrosis (LDH release) in a dose-dependent way, in a greater extent in the case of 6. Among the bacterial and fungal strains tested, only complex 6 presented antimicrobial activity against S. aureus Newman, indicating that this complex is a potential novel anticancer and antibacterial agent. These results delve into the structure-activity relationship of the complexes, considering molecular alterations such as replacing a phenyl group for a pyrazine group, and the inclusion of one or two cyanonitrile appendage groups, and their effects on biological activity. Overall, both complexes were found to be promising leads for the development of future anticancer drugs against low sensitive or cisplatin resistant tumors.
Publisher
MDPI AG,MDPI
Subject
Anti-Infective Agents - chemical synthesis
/ Anti-Infective Agents - chemistry
/ Anti-Infective Agents - pharmacology
/ Antineoplastic Agents - chemical synthesis
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ Coordination Complexes - chemistry
/ Coordination Complexes - pharmacology
/ Female
/ Gold
/ Humans
/ Ligands
