University Department of Pharmaceutical Sciences, Utkal University, Vani Vihar, Bhubaneswar 751004, Odisha, India.
University Department of Pharmaceutical Sciences, Utkal University, Vani Vihar, Bhubaneswar 751004, Odisha, India.
Bioorg Chem. 2019 Oct;91:103169. doi: 10.1016/j.bioorg.2019.103169. Epub 2019 Jul 30.
The continuous emergence and rapid spread of a multidrug-resistant strain of bacterial pathogens have demanded the discovery and development of new antibacterial agents. A highly conserved prokaryotic cell division protein FtsZ is considered as a promising target by inhibiting bacterial cytokinesis. Inhibition of FtsZ assembly restrains the cell-division complex known as divisome, which results in filamentation, leading to lysis of the cell. This review focuses on details relating to the structure, function, and influence of FtsZ in bacterial cytokinesis. It also summarizes on the recent perspective of the known natural and synthetic inhibitors directly acting on FtsZ protein, with prominent antibacterial activities. A series of benzamides, trisubstituted benzimidazoles, isoquinolene, guanine nucleotides, zantrins, carbonylpyridine, 4 and 5-Substituted 1-phenyl naphthalenes, sulindac, vanillin analogues were studied here and recognized as FtsZ inhibitors that act either by disturbing FtsZ polymerization and/or GTPase activity. Doxorubicin, from a U.S. FDA, approved drug library displayed strong interaction with FtsZ. Several of the molecules discussed, include the prodrugs of benzamide based compound PC190723 (TXA-709 and TXA707). These molecules have exhibited the most prominent antibacterial activity against several strains of Staphylococcus aureus with minimal toxicity and good pharmacokinetics properties. The evidence of research reports and patent documentations on FtsZ protein has disclosed distinct support in the field of antibacterial drug discovery. The pressing need and interest shall facilitate the discovery of novel clinical molecules targeting FtsZ in the upcoming days.
一种具有多重耐药性的细菌病原体的不断出现和快速传播，要求人们发现和开发新的抗菌药物。高度保守的原核细胞分裂蛋白 FtsZ 被认为是一个有前途的靶点，可以通过抑制细菌胞质分裂来实现。抑制 FtsZ 组装会抑制被称为分裂体的细胞分裂复合物，导致丝状化，从而导致细胞裂解。这篇综述重点介绍了与 FtsZ 在细菌胞质分裂中的结构、功能和影响相关的细节。它还总结了最近关于直接作用于 FtsZ 蛋白的已知天然和合成抑制剂的观点，这些抑制剂具有突出的抗菌活性。一系列苯甲酰胺、三取代苯并咪唑、异喹啉、鸟嘌呤核苷酸、嗪类、羰基吡啶、4 和 5-取代的 1-苯基萘、舒林酸、香草醛类似物都在这里进行了研究，并被认为是通过干扰 FtsZ 聚合和/或 GTPase 活性而起作用的 FtsZ 抑制剂。多柔比星，一种来自美国 FDA 批准的药物库，显示出与 FtsZ 的强烈相互作用。讨论的几种分子，包括苯甲酰胺基化合物 PC190723（TXA-709 和 TXA707）的前药。这些分子对几种金黄色葡萄球菌菌株表现出最显著的抗菌活性，毒性最小，药代动力学性质良好。关于 FtsZ 蛋白的研究报告和专利文献的证据，在抗菌药物发现领域提供了明确的支持。迫切的需求和兴趣将有助于在未来几天发现针对 FtsZ 的新型临床分子。
