Synthesis and Anticancer Activity of Ergosterol Peroxide Hybrids With Paclitaxel Side Chain Inducing Apoptosis in Human Hepatoma Carcinoma Cells

Natural Product Communications

卷:18

Original Research Paper

Xiaoshan Guo ; Wenkang Ren ; Zhen Lv ; Gang Li ; Hongling Li ; Mingrui Sun ; Xiaoming Li ; Gang Chen ; Zhiguo Zhang ; Wenting Zhang ; Ming Bu

[1] Department of Pharmacy, The Second Affiliated Hospital of , Qiqihar, China

[2] College of Pharmacy, , Qiqihar, China

[3] College of Psychiatry, , Qiqihar, China

[4] Department of Pharmacy, The Third Affiliated Hospital of , Qiqihar, China

[5] Research Institute of Medicine & Pharmacy, , Qiqihar, China

关键词: structure modification;    paclitaxel;    ergosterol peroxide;    hybrids;    antitumor;   

DOI  :  10.1177/1934578X231166778

 received in 2023-01-04, accepted in 2023-02-07,  发布年份 2023

来源: Sage Journals

【 摘 要 】

The antitumor activities of natural paclitaxel (PTX), semisynthetic docetaxel, and cabazitaxel are highly dependent on their C-13 side chains. Therefore, using natural ergosterol peroxide (EP, 1) as the lead compound, two EP-PTX hybrids (EP-A2 and EP-B2) were prepared and their antitumor activities were evaluated against 4 kinds of human MCF-7, HepG2, HCT-116, and A549 cell lines in vitro. The results showed that both EP-A2 and EP-B2 inhibited the growth of all four kinds of tested tumor cell lines. For paclitaxel-resistant MCF-7 cells, both EP-A2 and EP-B2 showed significant inhibitory activity with relatively low IC50 values (9.39 μM and 8.60 μM, respectively). In addition, EP-B2 inhibited the growth of the HepG2 cells (IC50 = 7.82 μM) more successfully than EP. Preliminary studies of the mechanism suggest that EP-B2 could arrest the G1 phase transition in HepG2 cells. In addition, EP-B2 showed an obvious apoptosis-inducing effect in HepG2 cells, as detected by the Annexin V/PI binding assay and the Western blot assay. Hybrid EP-B2 has the potential to become a novel antitumor drug through further study of the mechanism of action and its structural modifications.

【 授权许可】

CC BY-NC   
© The Author(s) 2023