Bandyopadhyay Debashis, Samano Selina, Villalobos-Rocha Juan Carlos, Sanchez-Torres Luvia Enid, Nogueda-Torres Benjamin, Rivera Gildardo, Banik Bimal K
Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, Texas 78539, United States.
Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F. Mexico.
Curr Med Chem. 2017;24(41):4714-4725. doi: 10.2174/0929867325666171201101807.
Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas' disease and leishmaniasis. Chagas' disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and millions of people are infected. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. On the other hand, Leishmaniasis represents complex diseases with an important clinical and epidemiological diversity. It is endemic in 88 countries 72 of which are developing countries and it has been estimated that are 12 million people infected and 350 million are in areas with infection risk. On this basis, research on organic compounds that can be used against these two diseases is an important target. A very simple, green, and efficient protocol is developed in which bismuth nitrate pentahydrate is employed as a Lewis acid catalyst in aqueous media under microwave irradiation for the synthesis of various 2-aryl substituted benzimidazoles from aldehydes and o-phenylenediamine. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and no wastes. Nine 1H-benzimidazole derivatives (1-9) with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by spectroscopic methods. The compounds were screened to identify whether they posses pharmacological activity against Chagas' disease and leishmaniasis. Compound 8 showed better activity than the control Nifurtimox against INC-5 Trypanosoma cruzi strain whereas compounds 3 and 9 have demonstrated potent leshmanicidal activity. A systematic green synthetic procedure and in vitro biological evaluation of nine 1H-benzimidazoles are described.
抗菌耐药性是全球范围内日益严重的问题，已经达到了严峻的程度。两种非常常见的被忽视热带病是恰加斯病和利什曼病。恰加斯病是一个严重的健康问题，主要发生在拉丁美洲，每年造成约50000人死亡，数百万人口感染。约25%-30%感染克氏锥虫的患者会发展为该疾病的慢性形式。另一方面，利什曼病是一类复杂的疾病，具有重要的临床和流行病学多样性。该病在88个国家呈地方性流行，其中72个是发展中国家，据估计有1200万人感染，3.5亿人处于感染风险地区。在此基础上，对可用于治疗这两种疾病的有机化合物的研究是一个重要目标。本文开发了一种非常简单、绿色且高效的方法，其中使用五水合硝酸铋作为路易斯酸催化剂，在微波辐射下于水介质中，由醛和邻苯二胺合成各种2-芳基取代的苯并咪唑。该方法的其他显著特点包括条件温和、原子经济性、易于萃取且无废物产生。合成了9种在2位和5位带有取代基的1H-苯并咪唑衍生物（1-9），并通过光谱方法阐明了化合物的结构。对这些化合物进行筛选，以确定它们是否具有抗恰加斯病和利什曼病的药理活性。化合物8对克鲁斯锥虫INC-5菌株显示出比对照药物硝呋莫司更好的活性，而化合物3和9已表现出强大的杀利什曼原虫活性。本文描述了一种系统的绿色合成方法以及对9种1H-苯并咪唑的体外生物学评价。
