Quest for Efficacious Next-Generation Taxoid Anticancer Agents and Their Tumor-Targeted Delivery

Journal of Natural Products
Iwao OjimaChangwei Wang

Abstract

Paclitaxel and docetaxel are among the most widely used chemotherapeutic drugs against various types of cancer. However, these drugs cause undesirable side effects as well as drug resistance. Therefore, it is essential to develop next-generation taxoid anticancer agents with better pharmacological properties and improved activity especially against drug-resistant and metastatic cancers. The SAR studies by the authors have led to the development of numerous highly potent novel second- and third-generation taxoids with systematic modifications at the C-2, C-10, and C-3' positions. The third-generation taxoids showed virtually no difference in potency against drug-resistant and drug-sensitive cell lines. Some of the next-generation taxoids also exhibited excellent potency against cancer stem cells. This account summarizes concisely investigations into taxoids over 25 years based on a strong quest for the discovery and development of efficacious next-generation taxoids. Discussed herein are SAR studies on different types of taxoids, a common pharmacophore proposal for microtubule-stabilizing anticancer agents and its interesting history, the identification of the paclitaxel binding site and its bioactive conformation, characteristi...Continue Reading

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Aug 29, 2020·Pharmaceutics·Alberto JuanCarlos Alonso-Moreno
Jun 19, 2019·Angewandte Chemie·Yusuke ImamuraMasayuki Inoue
Jan 12, 2021·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Luciana MoscaGianni Colotti
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Jan 19, 2021·ACS Biomaterials Science & Engineering·Jyothi B NairKaustabh Kumar Maiti
Nov 20, 2018·Organic Letters·Hiroaki MatobaMasayuki Inoue

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