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

Abstract

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 IC 50 s of 54.9 and 70.8 m mg/ml, respectively, whereas it exhibited no inhibitory activity for chitin synthase 3 up to 280 m mg/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 IC 50 s of 37.2 and 26.6 m mg/ml, respectively. Especially, the IC 50 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 (MIC‫61؍‬ m mg/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.

Plasma pharmacokinetics and metabolism of the antitumour drug candidate 2′-benzoyloxycinnamaldehyde in rats

“…BCA has also been isolated recently from the aerial parts of Pleuropterus ciliinervis Nakai (Polygonaceae) (Kang et al 2007). …”

“…The authors' studies further demonstrated that their anti-proliferative activity against tumour cells was mediated by induction of apoptosis via reactive oxygen species (ROS) (Han et al 2004) and inhibition of proteasome (Hong et al 2007). In addition, HCA was reported to have various other pharmacological activities including farnesyl protein transferase inhibition (Kwon et al 1996), anti-inflammatory activity (Lee et al 2005), immunomodulation (Koh et al 1998), and antifungal activity (Kang et al 2007). …”

Morphological Changes of the Filamentous Fungus Mucor Mucedo and Inhibition of Chitin Synthase Activity Induced by Anethole

“…In fact, micafungin was developed as a specific inhibitor of fungal glucan synthase in C. albicans and Aspergillus spp. (Denning, 2003;Kang et al, 2007). In addition, analysing unknown mechanisms of action for the development of novel antifungal drugs is thought to contribute to the elucidation of metabolic pathways or functions unique to filamentous fungi.…”

Natural Toxins for Use in Pest Management

“…Its mode of action is through inhibition of fungal cell wall formation by inhibition of chitin synthesis [67,68]. …”