Structural simplification of maytansine and synthesis efficiency for antitumor activity

Name: Uchida, Tomomi

Organization : Kobe University. Graduate School of Agricultural Science

Name: Fujimoto, Mayuka

Organization : Kobe University. Faculty of Agriculture

Name: Minamino, Maina

Organization : Kobe University. Faculty of Agriculture

Name: Kuse, Masaki

Organization : Kobe University. Graduate School of Agricultural Science

Email : kuse@eagle.kobe-u.ac.jp

keyword: Maytansine

LCSH: Antineoplastic agents

; Maytansinoids

Abstract: This study shows again the importance of the chemical synthesis of maytansine despite the decline in research following semi-synthetic advances in the 1980s. The renewed interest is due to the use of maytansine derivatives in antibody-drug conjugates (ADCs), particularly in trastuzumab emtansine (Kadcyla®), highlighting its clinical potential despite initial limitations caused by the potent cytotoxicity of maytansine. The binding site of maytansine differs from other anti-tumor agents; thus, we focused on this specificity. Based on the binding structure, the focus was on rational design, targeting non-critical moieties—specifically the dienyl structure and methoxy group-to be replaced with a simpler methylene chain. Computational simulations confirmed the stability of the designed analog, implying comparable activity to maytansine. The provided retrosynthetic analysis outlined a synthetic roadmap involving strategic transformations and critical steps such as aldol condensation. This study furthers the maytansine's binding mechanism and suggests a more efficient synthesis route for maytansine derivatives. The findings will offer potential advancements in ADC development, promoting maytansine's broader application in treating cancers and fostering improved clinical effectiveness

King Mongkut's University of Technology North Bangkok. Central Library

Address: BANGKOK

Email: library@kmutnb.ac.th

Created: 2024

Modified: 2024-12-04

Issued: 2024-12-04

บทความ/Article

application/pdf

BibliograpyCitation : In Kasetsart University. Faculty of Science. The Pure and Applied Chemistry International Conference 2024 (PACCON 2024) (pp.863-868). Bangkok : Kasetsart University, 2024

eng

©copyrights King Mongkut's University of Technology North Bangkok

ลำดับที่.	ชื่อแฟ้มข้อมูล	ขนาดแฟ้มข้อมูล	จำนวนเข้าถึง	วัน-เวลาเข้าถึงล่าสุด
1	PACCON 2024pp.863-868.pdf	330.11 KB

ใช้เวลา

0.032589 วินาที