Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies

Milena Simic; Nikola Paunovic; Ivan Boric; Jelena Randjelovic; Sandra Vojnovic; Jasmina Nikodinovic-Runic; Marina Pekmezovic; Vladimir Savic

doi:10.1016/j.bmcl.2015.08.086

Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies

Bioorg Med Chem Lett. 2016 Jan 1;26(1):235-9. doi: 10.1016/j.bmcl.2015.08.086. Epub 2015 Aug 31.

Authors

Milena Simic¹, Nikola Paunovic¹, Ivan Boric¹, Jelena Randjelovic¹, Sandra Vojnovic², Jasmina Nikodinovic-Runic², Marina Pekmezovic³, Vladimir Savic⁴

Affiliations

¹ University of Belgrade, Faculty of Pharmacy, Department of Organic Chemistry, Vojvode Stepe 450, 11221 Belgrade, Serbia.
² University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Microbial Molecular Genetics and Ecology, Vojvode Stepe 444a, P.P. Box 23, 11010 Belgrade, Serbia.
³ University of Belgrade, Faculty of Medicine, National Reference Medical Mycology Laboratory, Institute of Microbiology and Immunology, Dr Subotica 1, 11000 Belgrade, Serbia.
⁴ University of Belgrade, Faculty of Pharmacy, Department of Organic Chemistry, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: vladimir.savic@pharmacy.bg.ac.rs.

PMID: 26586600
DOI: 10.1016/j.bmcl.2015.08.086

Abstract

A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds.

Keywords: Antifungal compounds; Candida species; Isocoumarin derivatives.

Publication types

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

MeSH terms

Antifungal Agents / chemical synthesis*
Antifungal Agents / chemistry
Antifungal Agents / pharmacology*
Candida / cytology
Candida / drug effects*
Cell Line
Cell Survival / drug effects
Dose-Response Relationship, Drug
Humans
Isocoumarins / chemical synthesis*
Isocoumarins / chemistry
Isocoumarins / pharmacology*
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship

Substances

Antifungal Agents
Isocoumarins