Department of Medicinal Chemistry and Pharmacognosy, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Drug Dev Res. 2018 Mar;79(2):58-69. doi: 10.1002/ddr.21421. Epub 2017 Dec 29.
Hit, Lead & Candidate Discovery Glyoxalase-I (Glo-I) enzyme has emerged as a potential target for cancer treatment. Several classes of natural products including coumarins and flavonoids have shown remarkable Glo-I inhibitory activity. In the present study, computational and experimental approaches were used to explore the structure-activity relationships of a panel of 24 flavonoids as inhibitors of the Glo-1 enzyme. Scutellarein with an IC value of 2.04 μM was identified as the most potent inhibitor among the series studied. Di- or tri-hydroxylation of the benzene rings A and B accompanied with a C2/C3 double bond in ring C were identified as essential structural features for enzyme inhibition. Moreover, the ketol system showed a minor role in the inhibitory power of these compounds. The structure-activity relationships revealed in this study had deepened our understanding of the Glo-I inhibitory activities of flavonoids and opened the door for further exploration of this promising compound class.
已鉴定出，乙醛酸酶-I（Glo-I）酶已成为癌症治疗的一个潜在靶点。包括香豆素和类黄酮在内的几类天然产物已表现出显著的 Glo-I 抑制活性。在本研究中，使用计算和实验方法来探究了一组 24 种类黄酮作为 Glo-1 酶抑制剂的构效关系。研究中发现，具有 2.04 μM 的 IC 值的白杨素是系列中最有效的抑制剂。苯环 A 和 B 的二羟基化或三羟基化伴随着环 C 中的 C2/C3 双键被鉴定为抑制酶的必需结构特征。此外，酮醇系统在这些化合物的抑制能力中仅起到次要作用。本研究中揭示的构效关系加深了我们对类黄酮抑制 Glo-I 活性的理解，并为进一步探索这一有前途的化合物类别开辟了道路。
