discovery of hyaluronidase inhibitors from natural products and their mechanistic characterization under dmso-perturbed assay conditions：（透明质酸酶抑制剂的发现来自天然产物及其dmso-perturbed试验条件下的机械特性）.pdfVIP

Bioorganic Medicinal Chemistry Letters 27 (2017) 1620–1623 Contents lists available at ScienceDirect Bioorganic Medicinal Chemistry Letters journal homepage: www.else /locate/bmcl Discovery of hyaluronidase inhibitors from natural products and their mechanistic characterization under DMSO-perturbed assay conditions Keisuke Tomohara ⇑, Tomohiro Ito, Saika Onikata, Atsushi Kato, Isao Adachi ⇑ Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan a r t i c l e i n f o a b s t r a c t Article history: The present study discovered four novel hyaluronan-degrading enzyme (hyaluronidase) inhibitors Received 23 December 2016 including chikusetsusaponins and catechins through the activity-guided separation of Panax japonicus Revised 24 January 2017 and Prunus salicina, respectively. Although the discovery resulted in identification of usual frequent hit- Accepted 27 January 2017 ters, subsequent mechanistic characterizations under our DMSO-perturbed assay conditions and related Available online 31 January 2017 protocols revealed that chikusetusaponin IV would serve as an aggregating and non-specific binding inhi- bitor, while ()-epicatechin would interact specifically with enzyme at the catalytic site or more likely at Keywords: a kind of catechin-binding site with a relatively week inhibitory activity. The latter description might pro- Hyaluro