Inhibition of Chitin Synthases and Antifungal Activities by 2′-Benzoyloxycinnamaldehyde from Pleuropterus ciliinervis and Its Derivatives

• Published in: Biological & Pharmaceutical Bulletin Vol. 30; no. 3; pp. 598 - 602
• Main Authors: Kang, Tae Hoon, Hwang, Eui Il, Yun, Bong Sik, Park, Ki Duk, Kwon, Byoung Mog, Shin, Chul Soo, Kim, Sung Uk
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-03-2007; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: 2′-benzoyloxycinnamaldehyde; Acrolein - analogs & derivatives; Acrolein - chemistry; Acrolein - isolation & purification; Acrolein - pharmacology; Aminoglycosides - pharmacology; antifungal activity; Antifungal Agents - chemistry; Antifungal Agents - isolation & purification; Antifungal Agents - pharmacology; Benzoates - chemistry; Benzoates - isolation & purification; Benzoates - pharmacology; Candida - drug effects; Candida - growth & development; Chitin Synthase - antagonists & inhibitors; Chitin Synthase - metabolism; chitin synthase inhibitor; Cryptococcus neoformans - drug effects; Cryptococcus neoformans - growth & development; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Humans; Microbial Sensitivity Tests - methods; Molecular Structure; Plant Components, Aerial - chemistry; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Pleuropterus ciliinervis; Polygonaceae - chemistry; Pyrimidine Nucleosides - pharmacology
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.30.598

In the course of search for potent chitin synthase inhibitors from natural resources, a novel chitin synthases inhibitor, 2′-benzoyloxycinnamaldehyde (2′-BCA) (I), was isolated from the aerial parts of Pleuropterus ciliinervis NAKAI. 2′-BCA inhibited chitin synthase 1 and 2 of Saccharomyces cerevisiae with the IC50s of 54.9 and 70.8 μg/ml, respectively, whereas it exhibited no inhibitory activity for chitin synthase 3 up to 280 μg/ml. Its derivatives, 2′-chloro- (V) and 2(-bromo-cinnamaldehyde (VI), each showed 1.9 and 2.7-fold stronger inhibitory activities than 2′-BCA, with the IC50s of 37.2 and 26.6 μg/ml, respectively. Especially, the IC50 of compound VI against chitin synthase 2 represented 1.7-fold more potent inhibitory activity than polyoxin D, a well-known chitin synthase inhibitor. Furthermore, compounds V and VI showed potent antifungal activities against various fungi including human pathogenic fungi, with a particularly strong inhibitory activity against Cryptococcus neoformans (MIC=16 μg/ml). Although the chemical synthesis of this compound has been reported, the present study is the first report to describe the isolation of 2′-BCA from natural resources and chitin synthases inhibitory activities of its derivatives. These results suggested that 2′-BCA and its derivatives can potentially serve as useful lead compounds for development of antifungal agents.