Sofi Firdoos Ahmad, Tabassum Nahida
Department of Pharmaceutical Sciences, School of Applied Sciences and Technology, University of Kashmir, Srinagar, Jammu & Kashmir, India.
J Biomol Struct Dyn. 2023 Oct-Nov;41(17):8605-8628. doi: 10.1080/07391102.2022.2134212. Epub 2022 Oct 18.
Natural products have emerged as major leads for the discovery and development of new anti-cancer drugs. The plant-derived anti-cancer drugs account for approximately 60% and the quest for new anti-cancer agents is in progress. Anti-cancer leads have been isolated from plants, animals, marine organisms, and microorganisms from time immemorial. The process of semisynthetic modifications of the parent lead has led to the generation of new anti-cancer agents with improved therapeutic efficacy and minimal side effects. The various chemo-informatics tools, bioinformatics, high-throughput screening, and combinatorial synthesis are able to deliver the new natural product lead molecules. Plant-derived anticancer agents in either late preclinical development or early clinical trials include taxol, vincristine, vinblastine, topotecan, irinotecan, etoposide, paclitaxel, and docetaxel. Similarly, anti-cancer agents from microbial sources include dactinomycin, bleomycin, mitomycin C, and doxorubicin. In this review, we highlighted the importance of natural products leads in the discovery and development of novel anti-cancer agents. The semisynthetic modifications of the parent lead to the new anti-cancer agent are also presented. Further, the leads in the preclinical settings with the potential to become effective anticancer agents are also reviewed.Communicated by Ramaswamy H. Sarma.
天然产物已成为发现和开发新型抗癌药物的主要先导物。植物源抗癌药物约占60%，新型抗癌药物的探索工作正在进行中。自古以来，人们就从植物、动物、海洋生物和微生物中分离出抗癌先导物。对母体先导物进行半合成修饰的过程已产生了具有更高治疗效果和最小副作用的新型抗癌药物。各种化学信息学工具、生物信息学、高通量筛选和组合合成能够提供新的天然产物先导分子。处于临床前后期开发或早期临床试验阶段的植物源抗癌药物包括紫杉醇、长春新碱、长春碱、拓扑替康、伊立替康、依托泊苷、多西他赛等。同样，微生物源抗癌药物包括放线菌素、博来霉素、丝裂霉素C和阿霉素。在本综述中，我们强调了天然产物先导物在发现和开发新型抗癌药物中的重要性。还介绍了母体先导物向新型抗癌药物的半合成修饰。此外，还对临床前阶段有可能成为有效抗癌药物的先导物进行了综述。由拉马斯瓦米·H·萨尔马传达。
