Chagaleti Bharath Kumar, Reddy M B Rahul, Saravanan Venkatesan, B Shanthakumar, D Priya, Senthil Kumar P, Kathiravan M K
Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM IST Kattankulathur, Kancheepuram, Tamil Nadu, India.
Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India.
J Biomol Struct Dyn. 2023;41(23):14582-14598. doi: 10.1080/07391102.2023.2193985. Epub 2023 Mar 28.
Tuberculosis is a highly infectious disease other than HIV/AIDS and it is one of the top ten causes of death worldwide. Resistance development in the bacteria occurs because of genetic alterations, and the molecular insights suggest that the accumulation of mutation in the individual drug target genes is the primary mechanism of multi-drug resistant tuberculosis. Chorismate is an essential structural fragment for the synthesis of aromatic amino acids and synthesized biochemically by a number of bacteria, including Mycobacterium tuberculosis, utilizing the shikimate pathway. This shikimate kinase is the newer possible target for the generation of novel antitubercular drug because this pathway is expressed only in mycobacterium and not in Mammals. The discovery and development of shikimate kinase inhibitors provide an opportunity for the development of novel selective medications. Multiple shikimate kinase inhibitors have been identified via virtual screening and related protein-ligand interactions along with their studies. These inhibitors bind to the active site in a similar fashion to shikimate. In the current review, we present an overview of the biology and chemistry of the shikimate kinase protein and its inhibitors, with special emphasis on the various active scaffold against the enzyme. A variety of chemically diversified synthetic scaffolds including Benzothiazoles, Oxadiazoles, Thiobarbiturates, Naphthoquinones, Thiazoleacetonitriles, Hybridized Pyrazolone derivatives, Orthologous biological macromolecule derivatives, Manzamine Alkaloids derivatives, Dipeptide inhibitor, and Chalcones are discussed in detail. These derivatives bind to the specific target appropriately proving their potential ability through different binding interactions and effectively explored as an effective and selective Sk inhibitor.Communicated by Ramaswamy H. Sarma.
结核病是除艾滋病毒/艾滋病之外的一种高传染性疾病，是全球十大死因之一。细菌产生耐药性是由于基因改变，分子层面的见解表明，单个药物靶基因中突变的积累是耐多药结核病的主要机制。分支酸是芳香族氨基酸合成所必需的结构片段，包括结核分枝杆菌在内的许多细菌利用莽草酸途径通过生化方式合成。这种莽草酸激酶是开发新型抗结核药物的新的潜在靶点，因为该途径仅在分枝杆菌中表达，而在哺乳动物中不表达。莽草酸激酶抑制剂的发现和开发为新型选择性药物的开发提供了机会。通过虚拟筛选以及相关蛋白质-配体相互作用及其研究，已鉴定出多种莽草酸激酶抑制剂。这些抑制剂以与莽草酸相似的方式结合到活性位点。在本综述中，我们概述了莽草酸激酶蛋白及其抑制剂的生物学和化学性质，特别强调了针对该酶的各种活性支架。详细讨论了多种化学结构多样的合成支架，包括苯并噻唑、恶二唑、硫代巴比妥酸盐、萘醌、噻唑乙腈、杂化吡唑啉酮衍生物、直系同源生物大分子衍生物、曼赞胺生物碱衍生物、二肽抑制剂和查耳酮。这些衍生物与特定靶点适当结合，通过不同的结合相互作用证明了它们的潜在能力，并作为一种有效且选择性的莽草酸激酶抑制剂得到了有效探索。由拉马斯瓦米·H·萨尔马传达。
