Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
Italian Malaria Network, Centro Interuniversitario di Ricerche Sulla Malaria (CIRM), Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
Molecules. 2020 Mar 27;25(7):1530. doi: 10.3390/molecules25071530.
Malaria is a life-threatening disease and, what is more, the resistance to available antimalarial drugs is a recurring problem. The resistance of malaria parasites to previous generations of medicines has undermined malaria control efforts and reversed gains in child survival. This paper describes a continuation of our ongoing efforts to investigate the effects against strains and human microvascular endothelial cells (HMEC-1) of a series of methoxy -benzyl-substituted thiazinoquinones designed starting from a pointed antimalarial lead candidate. The data obtained from the newly tested compounds expanded the structure-activity relationships (SARs) of the thiazinoquinone scaffold, indicating that antiplasmodial activity is not affected by the inductive effect but rather by the resonance effect of the introduced group at the position of the benzyl substituent. Indeed, the current survey was based on the evaluation of antiparasitic usefulness as well as the selectivity on mammalian cells of the tested -benzyl-substituted thiazinoquinones, upgrading the knowledge about the active thiazinoquinone scaffold.
疟疾是一种危及生命的疾病，更糟糕的是，对抗疟药物的耐药性是一个反复出现的问题。疟原虫对前几代药物的耐药性破坏了疟疾控制工作，使儿童生存方面的成果付之东流。本文描述了我们正在进行的一项研究工作的延续，该研究工作旨在调查一系列甲氧基苄基取代的噻嗪并喹啉酮对疟原虫株和人微血管内皮细胞（HMEC-1）的作用。这些设计的化合物是以一种有针对性的抗疟先导候选药物为起点的。从新测试的化合物中获得的数据扩展了噻嗪并喹啉酮支架的构效关系（SARs），表明抗疟原虫活性不受诱导效应的影响，而是受苄基取代基 位引入基团的共振效应的影响。事实上，本研究是基于对被测试的甲氧基苄基取代的噻嗪并喹啉酮的抗寄生虫有用性以及对哺乳动物细胞的选择性进行评估的，提高了对活性噻嗪并喹啉酮支架的认识。
