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通过虚拟筛选和药敏试验鉴定对莽草酸脱氢酶的潜在抑制剂。

Identification of potential inhibitors against shikimate dehydrogenase through virtual screening and susceptibility test.

机构信息

Department of Pharmacy, Fujian Medical University, Fuzhou, China.

出版信息

J Enzyme Inhib Med Chem. 2024 Dec;39(1):2301768. doi: 10.1080/14756366.2024.2301768. Epub 2024 Jan 17.

Abstract

shikimate dehydrogenase (SaSDH) plays a crucial role in the growth of (), but absent in mammals and therefore a potential target for antibacterial drugs to treat drug-resistant infection. In this study, a 3D model of SaSDH was constructed by homology modelling and inhibitors of SaSDH were screened through virtual screening. (-)-Gallocatechin gallate and rhodiosin were identified as inhibitors with Ks of 2.47 μM and 73.38 μM, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a K of 44.65 μM for (-)-gallocatechin gallate and 16.45 μM for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 μg/mL for (-)-gallocatechin gallate and 250 μg/mL for rhodiosin against . The current findings have the potential for identification of drugs to treat infections by targeting SaSDH.

摘要

莽草酸脱氢酶(SaSDH)在()的生长中起着至关重要的作用,但在哺乳动物中不存在,因此是治疗耐药性()感染的抗菌药物的潜在靶标。在这项研究中,通过同源建模构建了 SaSDH 的 3D 模型,并通过虚拟筛选筛选了 SaSDH 的抑制剂。(-)-没食子儿茶素没食子酸酯和洛神花红素被鉴定为抑制剂,Ks 分别为 2.47 μM 和 73.38 μM。分子对接和等温滴定量热法表明,两种抑制剂均与 SaSDH 相互作用,(-)-没食子儿茶素没食子酸酯的 K 为 44.65 μM,洛神花红素的 K 为 16.45 μM。两种抑制剂均具有抗菌活性,(-)-没食子儿茶素没食子酸酯对的 MIC 为 50 μg/mL,洛神花红素对的 MIC 为 250 μg/mL。这些发现有可能通过靶向 SaSDH 来鉴定治疗()感染的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cc/10798293/9557bdc14122/IENZ_A_2301768_F0001_C.jpg

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