Hermann Theresa, Harzl Sarah, Wallner Robin, Prettner Elke, Pferschy-Wenzig Eva-Maria, Cal Monica, Mäser Pascal, Weis Robert
Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Schubertstraße 1, 8010 Graz, Austria.
Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstraße 8, 8010 Graz, Austria.
Pharmaceuticals (Basel). 2025 Jul 3;18(7):1004. doi: 10.3390/ph18071004.
: The benzamide from MMV's Malaria Box Project, the starting point of herein presented study, was initially tested against various strains as well as Gram-positive and Gram-negative bacteria. It exhibits multi-stage antiplasmodial potencies and lacks resistance development. : The favorable structural features from previous series were kept while the influence of the -Boc-piperazinyl substituent per se, as well as its ring position and its replacement by various heteroaromatic rings, was evaluated. Thus, this paper describes the preparation of the -derived 4'-(piperazin-1-yl)benzanilides for the first time, exhibiting broad-spectrum activity not only against plasmodia but also various bacterial strains. : A series of insightful structure-activity relationships were determined. Furthermore, pharmacokinetic and physicochemical parameters of the new compounds were determined experimentally or . Drug-likeliness according to Lipinski's rules was calculated as well. : A diarylthioether derivative of the lead compound was promisingly active against and exhibited broad-spectrum antibacterial activity against Gram-positive as well as Gram-negative bacteria. It is considered for testing against multi-resistant bacterial strains and studies.
MMV疟疾药物盒项目中的苯甲酰胺是本研究的起始点，最初对其针对各种疟原虫菌株以及革兰氏阳性和革兰氏阴性细菌进行了测试。它具有多阶段抗疟原虫效力且不易产生耐药性。保留了先前系列中有利的结构特征，同时评估了 -Boc-哌嗪基取代基本身的影响、其在环上的位置以及被各种杂芳环取代的情况。因此，本文首次描述了 -衍生的4'-(哌嗪-1-基)苯甲酰苯胺的制备，其不仅对疟原虫而且对各种细菌菌株都具有广谱活性。确定了一系列有见地的构效关系。此外，通过实验或其他方式确定了新化合物的药代动力学和物理化学参数。还根据Lipinski规则计算了药物相似性。先导化合物的二芳基硫醚衍生物对 具有有前景的活性，并且对革兰氏阳性和革兰氏阴性细菌均表现出广谱抗菌活性。它被考虑用于针对多重耐药细菌菌株的测试和 研究。
