Saklani Samriti, Chaudhari Shruti, Shukla Gayatri, Gound Harishankar, Awasarmol Dewashish, Taware Ravindra
Department of Natural Products, National Institute of Pharmaceutical Education and Research, Ahmedabad, Opposite Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India.
Mol Divers. 2024 Oct 30. doi: 10.1007/s11030-024-11018-0.
Parasitic diseases remain a significant global health challenge, especially in developing countries, contributing to approximately one million deaths annually. Notably, among the 143 FDA-approved antiparasitic drugs, thirty-four possess chlorine in their chemical structure, highlighting the importance of chlorine substitution. This underscores the significance of chlorine atoms in elucidating structure-activity relationships crucial for drug discovery, aiming to develop safer, more selective, and environmentally friendly molecules with enhanced efficacy. Of particular interest some are naturally occurring chlorinated metabolites derived from PKS, NRPS, and PKS-NRPS biosynthetic pathways, which offer the potential for further manipulation. However, there is limited literature on antiparasitic chlorinated compounds from microbial sources. To address this, we conducted a comprehensive literature survey from 1963 to the present, identifying 28 chlorinated compounds with confirmed antiparasitic properties. This review underscores the potential of enzymatic machinery for selective chlorine substitution, offering insights for biochemists and synthetic chemists to develop versatile chlorinated compounds through synthetic biology, combinatorial chemistry, and organic synthesis.
寄生虫病仍然是一项重大的全球健康挑战，尤其是在发展中国家，每年导致约100万人死亡。值得注意的是，在143种经美国食品药品监督管理局（FDA）批准的抗寄生虫药物中，有34种在其化学结构中含有氯，这凸显了氯取代的重要性。这强调了氯原子在阐明对药物发现至关重要的构效关系方面的重要性，旨在开发出更安全、更具选择性且对环境友好、疗效增强的分子。特别令人感兴趣的是一些源自聚酮合酶（PKS）、非核糖体肽合成酶（NRPS）和PKS-NRPS生物合成途径的天然存在的氯化代谢产物，它们具有进一步改造的潜力。然而，关于微生物来源的抗寄生虫氯化化合物的文献有限。为了解决这一问题，我们对1963年至今的文献进行了全面调查，确定了28种具有已证实抗寄生虫特性的氯化化合物。本综述强调了酶促机制进行选择性氯取代的潜力，为生物化学家和合成化学家通过合成生物学、组合化学和有机合成开发通用氯化化合物提供了见解。
