Design and synthesis of 1,3-diynes as potent antifungal agents against aspergillus fumigatus

TitleDesign and synthesis of 1,3-diynes as potent antifungal agents against aspergillus fumigatus
Publication TypeJournal Article
Year of Publication2023
AuthorsGoswami, L, Gupta, L, Paul, S, Vijayaraghavan, P, Bhattacharya, AK
JournalChemMedChem
Volume18
Issue9
Date PublishedMAY
Type of ArticleArticle
ISSN1860-7179
Keywords1, 3-Diynes, Antifungal agents, Aspergillus fumigatus, Cadiot-Chodkiewicz, Glaser-Hay
Abstract

Eugenol and isoeugenol, secondary metabolites isolated from the plant Myristica fragrans have displayed antifungal activities against Aspergillus fumigatus (IC50 1900 mu M). Compounds having conjugated unsaturation have been of great use as antifungals i. e. amphotericin B, nystatin and terbinafine etc. Hence, in the present study, we have designed and synthesised 1,3-diynes by utilizing Glaser-Hay and Cadiot-Chodkiewicz coupling reactions to furnish possible antifungal agents. Synthesis of 1,6-diphenoxyhexa-2,4-diyne derivatives was achieved by Cu(I) catalysed coupling of propargylated eugenol, isoeugenol, guaiacol, vanillin and dihydrogenated eugenol or eugenol in good to excellent yields. All the synthesized compounds were evaluated against pathogenic fungus A. fumigatus. Among all the synthesized compounds, one of the compounds was found to be exhibiting promising antifungal activity with IC50 value of 7.75 mu M thereby suggesting that this type of scaffold could pave the way for developing new antifungal agents. The most active compound was found to be low cytotoxic when assayed against L-132 cancer cell line. Effect of the most active compound on ergosterol biosynthesis has also been studied. Also, the most active compound exhibited significant anti-biofilm activity although the concentration was found to be higher than its anti-fungal activity. Morphological changes in the biofilm were remarkable under confocal laser scanning microscopy.

DOI10.1002/cmdc.202300013
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

3.540

Divison category: 
Organic Chemistry
Database: 
Web of Science (WoS)

Add new comment