Synthesis, anti-leukemia activity, and molecular docking of novel 3,16-androstenedione derivatives

Dongjie Chen; Jiaying Huang; Shanshan Xiao; Guiguang Cheng; Yaping Liu; Tianrui Zhao; Caixia Chen; Yongxin Yi; Yungui Peng; Jianxin Cao

doi:10.1016/j.steroids.2023.109290

Synthesis, anti-leukemia activity, and molecular docking of novel 3,16-androstenedione derivatives

Steroids. 2023 Nov:199:109290. doi: 10.1016/j.steroids.2023.109290. Epub 2023 Aug 6.

Authors

Affiliations

¹ Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
² Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
³ Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address: pyg@swu.edu.cn.
⁴ Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China. Electronic address: jxcao321@hotmail.com.

PMID: 37549776
DOI: 10.1016/j.steroids.2023.109290

Abstract

In this study, we synthesized androsta-4,14-diene-3,16-dione, 12β-hydroxyandrosta-4,14-diene-3,16-dione, and other 3,16-androstenedione derivatives from commercially available dehydroepiandrosterone as a starting material in 9-13 steps with high yields. The bioactivity of the obtained compounds was evaluated. Compounds 14a and 23a were shown to have high antitumor activity against acute lymphoblastic leukemia cell lines Nalm-6 and BALL-1, respectively. Network pharmacology analysis showed that the anti-leukemia activity of compounds 14a and 23a might be related to the JAK2, ABL1 protein, and PI3K/Akt signaling pathways. The molecular docking of compounds 14a and 23a identified possible active sites, with the lowest docking scores for PTGS2 and MAPK14, respectively. In addition, the absorption, distribution, metabolism, and excretion prediction results revealed the drug-likeness of the two compounds. Therefore, compounds 14a and 23a should be considered anti-leukemia candidates in future studies.

Keywords: 3,16-androstenedione derivatives; Acute lymphoblastic leukemia; Androsta-4,14-diene-3,16-dione; Molecular docking; Network pharmacology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androstenedione*
Molecular Docking Simulation
Phosphatidylinositol 3-Kinases* / metabolism
Signal Transduction

Substances

Androstenedione
Phosphatidylinositol 3-Kinases