Palladium-Catalyzed Synthesis and Anticancer Activity of Paclitaxel-Dehydroepiandrosterone Hybrids

Sheng-Jie Lou; Xiao-Huan Li; Xian-Li Zhou; Dong-Mei Fang; Feng Gao

doi:10.1021/acsomega.0c00558

Palladium-Catalyzed Synthesis and Anticancer Activity of Paclitaxel-Dehydroepiandrosterone Hybrids

ACS Omega. 2020 Mar 9;5(10):5589-5600. doi: 10.1021/acsomega.0c00558. eCollection 2020 Mar 17.

Authors

Sheng-Jie Lou¹, Xiao-Huan Li¹, Xian-Li Zhou¹, Dong-Mei Fang², Feng Gao¹

Affiliations

¹ School of Life Science and Engineering, Southwest Jiaotong University, No. 111, Erhuan Road, Chengdu 610031, PR China.
² Chengdu Institute of Biology, Chinese Academy of Sciences, No. 9, Section 4, South Renmin Road, Chengdu 610041, PR China.

Abstract

According to the activity-structure relationship of the C-13 side chain in paclitaxel or docetaxel, eighteen novel paclitaxel-dehydroepiandrosterone (DHEA) hybrids were designed and synthesized by Pd(II)-catalyzed Suzuki-Miyaura cross-coupling of 17-trifluoromethanesulfonic enolate-DHEA with different aryl boronic acids. The in vitro anticancer activity of the hybrids against a human liver cancer cell line (HepG-2) was evaluated by MTT assay, showing that most of these hybrids possessed moderate antiproliferative activity against the HepG-2 cancer cell line. Among these hybrids, three ones (7b, 7g, and 7i) with ortho-substituents in the phenyl group of the D-ring of DHEA analogues exhibited moderate anticancer activity. The optimal compound 7i showed superior anticancer activity against the HepG-2 cell line with an IC₅₀ value of 26.39 μM.