Molecular docking studies on analogues of quercetin with alanine:alanine ligase of Helicobacter pylori
Molecular docking studies on analogues of quercetin with alanine:alanine ligase of Helicobacter pylori
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DOI：
10.1007/s00044-012-0207-7
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发表时间：
2013-05-01
影响因子：
2.6
通讯作者：
Karak, Niranjan
中科院分区：
文献类型：
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作者：
Singh, Salam Pradeep;Konwarh, Rocktotpal;Karak, Niranjan
幽门螺杆菌(Hp)是一种与多种疾病相关的人类病原体，如胃炎、消化性溃疡、痔疮和胃癌。幽门螺杆菌对抗菌药的耐药性已与世界范围内的其他病原体一样增加，因此迫切需要开发新的抗菌剂。D-丙氨酸：D-丙氨酸连接酶(DDL，EC 6.3.2.4)一直被认为是一种潜在的抗菌药物靶点，并进行了大量的抑制剂筛选工作。栎素是黄酮类化合物中的一员，其特征是由两个苯环通过杂环吡喃酮环连接而成的黄酮核，具有抗幽门螺杆菌DDL(HpDdl)酶的活性。在此环境下，我们进行了Qetetin及其类似物在HpDd1活性部位的分子对接分析。部分化合物与HpDdl酶有较好的亲和力和相互作用。对接分析和吸收、分布、代谢及毒性研究进展较少，作为可能的先导分子或一类具有增强药理性质的新型药物。
Helicobacter pylori (Hp) is a human pathogen associated with myriad of diseases such as gastritis, peptic ulceration, piles and gastric cancer. The resistance of Hp against antimicrobial agents has increased just as that of other pathogens worldwide, thus emphasizing an urgent need for developing new antibacterial agents. The d-alanine:d-alanine ligase (Ddl, EC 6.3.2.4) has been considered as a putative antimicrobial drug target and a lot of inhibitor screening efforts have been made. Quercetin, a member of the flavonoids, characterized by a flavone nucleus composed of two benzene rings linked through a heterocyclic pyrone ring is reported to possess antibacterial activity against H. pylori Ddl (HpDdl) enzyme. In this milieu, we have performed molecular docking analysis of quercetin and its analogues at the active site of HpDdl. Some of the screened compounds showed better affinity and interaction with HpDdl enzyme. The docking analysis and absorption, distribution, metabolism and toxicity study forward few of them as plausible lead molecule or a novel class of drugs with enhanced pharmacological properties.