Rock Jonathan, Garcia Daniel, Espino Omar, Shetu Shaila A, Chan-Bacab Manuel J, Moo-Puc Rosa, Patel Navin B, Rivera Gildardo, Bandyopadhyay Debasish
Department of Chemistry, University of Texas Rio Grande Valley, Edinburg, TX, United States.
Departamento de Microbiología Ambiental y Biotecnología, Universidad Autónoma de Campeche, Campeche, México.
Front Chem. 2021 Sep 17;9:725892. doi: 10.3389/fchem.2021.725892. eCollection 2021.
World Health Organization (WHO) identified twenty tropical disease categories as neglected tropical diseases (NTDs). Chagas' disease (also known as American trypanosomiasis) and leishmaniasis are two major classes of NTDs. The total number of mortality, morbidity, and disability attributed each year due to these two categories of diseases in magnitudes is much higher than the so-called elite diseases like cancer, diabetes, AIDS, cardiovascular and neurodegenerative diseases. Impoverished communities around the world are the major victim of NTDs. The development of new and novel drugs in the battle against Chagas' disease and leishmaniasis is highly anticipated. An easy and straightforward on-water green access to synthesize benzopyrazines is reported. This ultrasound-assisted procedure does not require any catalyst/support/additive/hazardous solvents and maintains a high atom economy. A series of eleven benzopyrazines has been synthesized, and most of the synthesized compounds possess the drug-likeness following Lipinski's "Rule of 5". Benzopyrazines and demonstrated moderate leishmanicidal activity against (M378) strain. The selective lead compound showed good leishmanicidal, and trypanocidal activities () against both (M378) and (NINOA) strains compared to the standard controls. The trypanocidal and leishmanicidal activities of the lead compound have been validated by molecular docking studies against four biomolecular drug targets histidyl-tRNA synthetase, -sialidase, leishmanial rRNA A-site, and leishmania major -myristoyl transferase.
世界卫生组织（WHO）将二十种热带病类别确定为被忽视的热带病（NTDs）。恰加斯病（也称为美洲锥虫病）和利什曼病是两类主要的被忽视的热带病。每年由于这两类疾病导致的死亡、发病和残疾总数在数量级上远高于癌症、糖尿病、艾滋病、心血管疾病和神经退行性疾病等所谓的“精英疾病”。世界各地的贫困社区是被忽视的热带病的主要受害者。人们高度期待在对抗恰加斯病和利什曼病的战斗中开发新的和新颖的药物。本文报道了一种简单直接的水上绿色合成苯并吡嗪的方法。这种超声辅助方法不需要任何催化剂/载体/添加剂/有害溶剂，并且保持了高原子经济性。已经合成了一系列十一种苯并吡嗪，并且大多数合成化合物符合Lipinski的“五规则”，具有药物相似性。苯并吡嗪 和 对（M378）菌株表现出中等的杀利什曼原虫活性。与标准对照相比，选择性先导化合物 对（M378）和（NINOA）菌株均表现出良好的杀利什曼原虫和杀锥虫活性（）。通过针对四种生物分子药物靶点（组氨酰 - tRNA合成酶、 - 唾液酸酶、利什曼原虫rRNA A位点和硕大利什曼原虫 - 肉豆蔻酰转移酶）的分子对接研究，验证了先导化合物 的杀锥虫和杀利什曼原虫活性。
