Benzimidazole tethered pyrrolo[3,4-b]quinoline with broad-spectrum activity against fungal pathogens

Pedro Villa; Natarajan Arumugam; Abdulrahman I Almansour; Raju Suresh Kumar; S M Mahalingam; Keiji Maruoka; Shankar Thangamani

doi:10.1016/j.bmcl.2019.01.006

Benzimidazole tethered pyrrolo[3,4-b]quinoline with broad-spectrum activity against fungal pathogens

Bioorg Med Chem Lett. 2019 Mar 1;29(5):729-733. doi: 10.1016/j.bmcl.2019.01.006. Epub 2019 Jan 9.

Authors

Pedro Villa¹, Natarajan Arumugam², Abdulrahman I Almansour³, Raju Suresh Kumar⁴, S M Mahalingam⁵, Keiji Maruoka⁶, Shankar Thangamani⁷

Affiliations

¹ Midwestern University, Glendale, AZ 85308, United States.
² Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: antarajan@ksu.edu.sa.
³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: almansor@ksu.edu.sa.
⁴ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: sraju@ksu.edu.sa.
⁵ Deparatment of Chemistry, SRM Institute of Science and Technology, Kattankulathur, Kancheepuram 603203, India.
⁶ Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan. Electronic address: maruoka@kuchem.kyoto-u.ac.jp.
⁷ Department of Pathology and Population Medicine, College of Veterinary Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, United States. Electronic address: sthang@midwestern.edu.

PMID: 30655213
DOI: 10.1016/j.bmcl.2019.01.006

Abstract

Fungal infections caused by Candida and Cryptococcus are particularly dangerous for immunocompromised individuals. In this study, we identified that benzimidazole fused pyrrolo[3,4-b]quinoline compounds have potent antifungal activity against several clinical isolates of pathogenic fungal strains. Specifically, the compound 6a did not show cytotoxicity against mammalian cells at a concentration that inhibits the growth of fungal strains. In addition, the compound 6a also significantly reduced the metabolic activity of fungal cells in the Candida albicans biofilms. Collectively, our results indicate that benzimidazole fused quinoline compounds have a potential to develop as an antifungal agents.

Keywords: Antifungal agent; Benzimidazole fused pyrroloquinoline; Povarov reaction; Toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antifungal Agents / pharmacology*
Benzimidazoles / chemistry*
Biofilms / drug effects
Candida albicans / drug effects*
Cryptococcus / drug effects*
Microbial Sensitivity Tests
Pyrroles / chemistry*
Quinolines / chemistry*

Substances

Antifungal Agents
Benzimidazoles
Pyrroles
Quinolines
pyrroloquinoline