1486-66-4Relevant articles and documents
Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM Inhibitors
Villaume, Sydney A.,Fu, Jian,N'Go, Inès,Liang, Hui,Lou, Huayong,Kremer, Laurent,Pan, Weidong,Vincent, Stéphane P.
supporting information, p. 10423 - 10429 (2017/08/07)
This study reports a novel class of inhibitors of uridine 5′-diphosphate (UDP) galactopyranose mutase (UGM) derived from a screening of natural products. This enzyme is an essential biocatalyst involved in the cell wall biosynthesis of Mycobacterium tuberculosis. Flavonoids are potent inhibitors of UGM. The synthesis of novel methylated flavonoids allowed a structure–activity relationship analysis to be performed and which functional groups and structural elements were required for UGM inhibition could be determined. The binding mode of one of the best inhibitors was found to be noncompetitive. Docking simulations indicated that this molecule was likely to bind UGM in its open conformation, in a cavity recently identified as a “druggable” pocket. Importantly, two of the best inhibitors of the M. tuberculosis UGM displayed moderate activity against whole M. tuberculosis cells. This study reports the first natural products that act as inhibitor of UGM. Given the importance of natural products in medicinal chemistry, these results create new opportunities for the discovery of new antitubercular agents.
Metabolism-based synthesis, biologic evaluation and SARs analysis of O-methylated analogs of quercetin as thrombin inhibitors
Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Wei-Li,Lian-Yin,Yang, Jian-Ping,Hao-Tang,Duan, Jin-Ao
experimental part, p. 210 - 222 (2012/09/07)
In blood, quercetin is mainly found in metabolized forms. In order to study the activities of these quercetin metabolites in cardiovascular disease, 17 methylquercetin derivatives were synthesized based on metabolism in vivo, their thrombin inhibition activity were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The results showed that 6 methylquercetin derivatives had stronger inhibitory activities than that of quercetin. Preliminary SARs analysis showed that hydroxyl groups at C-3′ and C-4′ position in the B-ring and hydroxyl group at C-3 position in the C-ring played key roles in the thrombin inhibitory activity. The findings of this study would provide information for the exploitation and utilization of quercetin as thrombin inhibitor for thrombotic disease treatment.
