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聚酮合酶 13(Pks13)抑制:新型抗结核药物的潜在靶点。

Polyketide Synthase 13 (Pks13) Inhibition: A Potential Target for New Class of Anti-tubercular Agents.

机构信息

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli, Uttar Pradesh, 226002, India.

出版信息

Curr Top Med Chem. 2024;24(27):2362-2376. doi: 10.2174/0115680266322983240906055750.

Abstract

Tuberculosis is one of the deadly infectious diseases that has resurfaced in multiple/ extensively resistant variants (MDR/XDR), threatening humankind. Today's world has a higher prevalence of tuberculosis (TB) than it has ever had throughout human history. Due to severe adverse effects, the marketed medications are not entirely effective in these forms. So, developing new drugs with a promising target is an immense necessity. Pks13 has emerged as a promising target for the mycobacterium. The concluding step of mycolic acid production involved Pks13, a crucial enzyme that helps form the precursor of mycolic acid via the Claisen-condensation reaction. It has five domains at the active site for targeting the enzyme and is used to test chemical entities for their antitubercular activity. Benzofurans, thiophenes, coumestans, N-phenyl indoles, and β lactones are the ligands that inhibit the Pks13 enzyme, showing potential antitubercular properties.

摘要

结核病是一种致命的传染病,已经出现了多种/广泛耐药变体(MDR/XDR),威胁着人类。当今世界的结核病(TB)患病率高于人类历史上的任何时期。由于严重的副作用,市场上的药物在这些形式下并不完全有效。因此,开发具有有前途目标的新药是当务之急。Pks13 已成为分枝杆菌的一个有希望的靶标。Mycolic 酸生成的最后一步涉及 Pks13,这是一种关键酶,通过 Claisen 缩合反应帮助形成 Mycolic 酸的前体。它在活性部位有五个结构域,用于针对酶,并用于测试化学实体的抗结核活性。苯并呋喃、噻吩、香豆素、N-苯基吲哚和β内酰胺是抑制 Pks13 酶的配体,显示出潜在的抗结核特性。

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