Synthesis and biological evaluation of BU-4664L derivatives as potential anticancer agents

Bioorg Med Chem Lett. 2022 Jan 1:55:128474. doi: 10.1016/j.bmcl.2021.128474.

Chao Liu ¹, Yuan-Yuan Xu ², Zhao-Hui Wen ², Yue-Hui Dong ³, Zhao-Peng Liu ⁴

Affiliations

1 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China. Electronic address: chaoliu@sdu.edu.cn.
2 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
3 Jinan Vocational College of Nursing, Jinan 250102, PR China.
4 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China. Electronic address: liuzhaop@sdu.edu.cn.

PMID: 34838651 DOI: 10.1016/j.bmcl.2021.128474

Abstract

BU-4664L is a naturally occurring N-farnesylated dibenzodiazepinone with important biological activities. Herein, we report the synthesis and antitumor evaluation of two series of BU-4664L derivatives bearing different substituent patterns on the dibenzodiazepinone core and with diverse side chains. All of the derivatives displayed micromolar activity against the human prostate Cancer PC-3 cells, while lower or no activity against the human lung H460 cells. The most active derivatives were 10a and 16c which exerted antiproliferative activity against PC-3 cells with GI₅₀ values of 5.66 and 5.94 μM, respectively, and thus represent promising lead compounds for further development.

Keywords

Anticancer agents; BU-4664L; Diazepinomicin; ECO-4601; TLN-4601.

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