Privileged fragment-based design, synthesis and in vitro antitumor activity of imatinib analogues

Hongyu Jiang; Yuankun Wang; Maokai Jiang; Lei Yao

doi:10.55730/1300-0527.3549

Privileged fragment-based design, synthesis and in vitro antitumor activity of imatinib analogues

Turk J Chem. 2023 Feb 14;47(2):426-435. doi: 10.55730/1300-0527.3549. eCollection 2023.

Authors

Hongyu Jiang¹, Yuankun Wang¹, Maokai Jiang¹, Lei Yao¹

Affiliation

¹ School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shan-dong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, China.

Abstract

Based on the privileged fragment-based drug design strategy, a series of imatinib analogues bearing the moiety of 3-(2-amino-2-oxoacetyl)-1H-indole were designed and synthesized, and the in vitro antitumor activity of these compounds was detected by MTT method using K562 (human myeloid leukemia) and K562R (imatinib-resistant chronic myeloid leukemia) cell lines. Molecular docking was used to preliminarily explain the possible binding modes. The most potent compound I2 exhibited better antitumor activity than those of imatinib against K562 and K562R cancer cells with IC₅₀ values of 0.8 μM and 0.7 μM.

Keywords: Privileged fragment-based drug design; antitumor; imatinib; synthesis.