Inhibition of chitin synthases and antifungal activities by 2'-benzoyloxycinnamaldehyde from Pleuropterus ciliinervis and its derivatives.
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 microg/ml, respectively, whereas it exhibited no inhibitory activity for chitin synthase 3 up to 280 microg/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 microg/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 microg/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.
Kang
Tae Hoon
TH
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Hwang
Eui Il
EI
Yun
Bong Sik
BS
Park
Ki Duk
KD
Kwon
Byoung Mog
BM
Shin
Chul Soo
CS
Kim
Sung Uk
SU
D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000617:Aminoglycosides / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects / Q000254:growth & development; D002687:Chitin Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D015394:Molecular Structure; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019664:Polygonaceae / Q000737:chemistry*; D011741:Pyrimidine Nucleosides / Q000494:pharmacology
C484327:2'-benzoyloxycinnamaldehyde; C522108:2'-chlorocinnamaldehyde; C522109:2-bromocinnamaldehyde; D000617:Aminoglycosides; D000935:Antifungal Agents; D001565:Benzoates; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011741:Pyrimidine Nucleosides; D000171:Acrolein; C011952:nikkomycin; C002458:polyoxorim; D002687:Chitin Synthase; C400821:chitin synthase 2