Synthesis and Bioactivity Investigation of Quinone-based Dimeric Cationic Triazolium Amphiphiles Selective against Resistant Fungal and Bacterial Pathogens

Authors

Jaya P. Shrestha, Utah State University
Coleman Baker, Utah State UniversityFollow
Yukie Kawasaki, Utah State UniversityFollow
Yagya Prasad Subedi, Utah State University
Vincent P. N. Nziko, Utah State University
Jon Y. Takemoto, Utah State UniversityFollow
Cheng-Wei Tom Chang, Utah State UniversityFollow

Document Type

Article

Journal/Book Title

European Journal of Medicinal Chemistry

Publication Date

1-27-2017

Publisher

Elsevier

Volume

126

First Page

696

Last Page

704

Abstract

A series of synthetic dimeric cationic anthraquinone analogs (CAAs) with potent antimicrobial activities against a broad range of fungi and bacteria were developed. These compounds were prepared in 2–3 steps with high overall yield and possess alkyl chain, azole, quinone, and quaternary ammonium complexes (QACs). In vitro biological evaluations reveal prominent inhibitory activities of lead compounds against several drug-susceptible and drug-resistant fungal and bacterial strains, including MRSA, VRE, Candida albicans and Aspergillus flavus. Mode of action investigation reveals that the synthesized dimeric CAA's can disrupt the membrane integrity of fungi. Computational studies reveal possible designs that can revive the activity of QACs against drug-resistant bacteria. Cytotoxicity assays in SKOV-3, a cancer cell line, show that the lead compounds are selectively toxic to fungi and bacteria over human cells.

Comments

PubMed PMID: 27951483

Recommended Citation

Shrestha, J. P.; Baker, C.; Kawasaki, Y.; Subedi,Y. P.; Nziko, V. P.; Takemoto, J. Y.; Chang, C.-W. T. “Synthesis and Bioactivity Investigation of Quinone-based Dimeric Cationic Triazolium Amphiphiles Selective against Resistant Fungal and Bacterial Pathogens.” Eur. J. Med. Chem. 2017, 126, 696-704. PubMed PMID: 27951483.