Recent advances in microbially derived chlorinated antiparasitic compounds.

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-10-30 DOI:10.1007/s11030-024-11018-0
Samriti Saklani, Shruti Chaudhari, Gayatri Shukla, Harishankar Gound, Dewashish Awasarmol, Ravindra Taware
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Abstract

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.

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微生物衍生氯化抗寄生虫化合物的最新进展。
寄生虫病仍然是全球健康的重大挑战,尤其是在发展中国家,每年造成约 100 万人死亡。值得注意的是,在美国食品及药物管理局批准的 143 种抗寄生虫药物中,有 34 种药物的化学结构中含有氯,这凸显了氯替代的重要性。这凸显了氯原子在阐明结构-活性关系方面的重要意义,而结构-活性关系对于药物发现至关重要,其目的是开发出更安全、更具选择性、更环保且药效更强的分子。尤其令人感兴趣的是,从 PKS、NRPS 和 PKS-NRPS 生物合成途径中天然产生的氯化代谢物,具有进一步操纵的潜力。然而,有关微生物来源的抗寄生虫氯化化合物的文献十分有限。为了解决这个问题,我们对 1963 年至今的文献进行了全面调查,确定了 28 种已证实具有抗寄生虫特性的氯化化合物。这篇综述强调了酶机制在选择性氯置换方面的潜力,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多功能氯化化合物提供了启示。
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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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