{"title":"Recent advances in microbially derived chlorinated antiparasitic compounds.","authors":"Samriti Saklani, Shruti Chaudhari, Gayatri Shukla, Harishankar Gound, Dewashish Awasarmol, Ravindra Taware","doi":"10.1007/s11030-024-11018-0","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-024-11018-0","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
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.
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;