Novel triazole analogs of apigenin‑7‑methyl ether exhibit potent antitumor activity against ovarian carcinoma cells via the induction of mitochondrial‑mediated apoptosis

Abstract

Ovarian cancer is one of the main causes of cancer-associated mortality across the world. Currently, ovarian cancer is mainly treated with chemotherapy. However, ovarian cancer is detected at advanced stages and chemotherapy has numerous side effects. In addition, the results of current chemotherapy on the treatment of ovarian cancer are less than satisfactory. Therefore, there is an urgent need to develop novel and more viable chemotherapeutic agents that can be used to treat ovarian cancer. The present study was designed to synthesize a series of novel triazole analogs of the bioactive apigenin-7-methyl ether to evaluate its anticancer activity against three human ovarian cancer cell lines. A total of eight novel triazole derivatives were synthesized and screened for their anticancer activity. Of all the derivatives, a derivative named 3d exhibited significant and dose-dependent anticancer activity against the SKOV3 ovarian cancer cell line. The IC50 of 3d was found to be 10 µM against the SKOV3 cancer cell line. It was also observed that 3d induced apoptosis in SKOV3 cancer cells through the accretion of reactive oxygen species and reduction in mitochondrial membrane potential. The molecule also modulated the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein. Taken together, these results showed that the apigenein-7-methyl ether novel derivative 3d may prove an important lead molecule for the treatment of ovarian cancer.

Application of triazoles in the structural modification of natural products

“…Qi et al. 67 found that novel triazole analogs of apigenin-7-methyl ether exhibit potent antitumor activity against ovarian carcinoma cells via the induction of mitochondria-mediated apoptosis. Of all the derivatives, the derivative 14 ( Figure 6 ) exhibited significant and dose-dependent anticancer activity against the SKOV3 ovarian cancer cell line.…”

Recent Advances in Bioactive Flavonoid Hybrids Linked by 1,2,3-Triazole Ring Obtained by Click Chemistry

“…Flavone derivatives 37a – 37g ( Figure 13 ) of apigenin-7-methyl ether were synthesized by CuAAC reaction between O -propargylated flavone and substituted azides. These compounds exhibited antiproliferative activity against ovarian cancer cell lines SKOV3, OVCAR-3 and Caov-3 (10 < IC 50 < 40 µM) [ 78 ]. Hybrid 37a showed the highest antiproliferative activity against all cancer cells (IC 50 = 10, 15 and 20 µM for SKOV3, OVCAR-3 and Caov-3, respectively) and was found to induce apoptosis on SKOV3 cells through ROS-mediated alterations in mitochondrial membrane potential (MMP), and modulated the expression of Bcl-2 and Bax proteins [ 78 ].…”

Click Chemistry in Natural Product Modification

“…Rao et al reported that the flavone/imidazole-triazole derivative G3 could exert moderate antiproliferative activity against MCF-7 cancer cells (IC 50 = 17.9 μ M) ( Rao et al, 2018 ). Chen et al reported that apigenin-triazole G4 could exert inhibitory activity against SKOV-3 cells (IC 50 = 10 μ M) ( Qi et al, 2018 ). Mechanistic studies indicated that G4 could promote the level of cellular reactive oxygen species (ROS) and reduce the mitochondrial membrane potential, thereby inducing the apoptosis of SKOV-3 cells.…”