Design, Synthesis, and Anticancer Activity of Natural Product Hybrids With Paclitaxel Side Chain Inducing Apoptosis in Human Colon Cancer Cells

Abstract

Based on the strong activity dependence of paclitaxel (PTX; Taxol) or docetaxel (Taxotere) on the C-13 side chain, a small library of dehydroepiandrosterone, cholesterol, vitamin D2, and alkaloids talatisamine and songorine-PTX hybrids have been synthesized and evaluated for in vitro anticancer activity by MTT assay against human breast (MCF-7), colon (HCT116), lung carcinoma (A549), and renal adenocarcinoma (786-0) cancer cell lines. Most hybrids (11b, 12b, 13b, 15b, and 18b) reduced the growth of MCF-7 and 786-0 cells with low PTX sensitivity in vitro. Among the synthesized compounds, hybrid 11b was better in inhibiting the growth of the 4 cells than PTX. A relatively low IC50 value of compound 11b (8.16 ± 0.04 μM) was also examined after exposure for 48 hours. Hybrid 11b showed a proapoptotic effect in HCT116 cells evaluated by Annexin V/propidium iodide binding assay. The level of hybrid 11b leading to protective cell death in HCT116 cells was detected using western blot and not easily observed in our basic examinations.

Improving Properties of Podophyllic Aldehyde-Derived Cyclolignans: Design, Synthesis and Evaluation of Novel Lignohydroquinones, Dual-Selective Hybrids against Colorectal Cancer Cells

“…The combination of different chemical entities with expected synergistic or dual effects also constitutes a promising strategy to avoid resistances or to discover new treatments in cancer therapy [ 19 ]. Thus, different natural products with diverse structures, origins, and mechanisms of action have been combined to create new bioactive entities [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Among the variety of natural products, lignans have contributed to remarkable advances in the discovery of new plant-derived drugs, particularly naphthalene cyclolignans, whose main representative is podophyllotoxin [ 27 ].…”

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

“…For PTX-resistant human mammary glands (MCF-7), most compounds were superior to PTX in inhibiting cell line growth. [25][26][27] These benefits encourage us to further synthesize taxane-like natural skeleton-C13 side chain hybrids and we expect to extend the therapeutic use of PTX to PTX-resistant or insensitive tumors.…”

Taxus yunnanensis genome offers insights into gymnosperm phylogeny and taxol production

“…Taxus are well-known for their cancer-inhibitory alkaloid paclitaxel (Taxol), which is a trace natural product 1 . Taxol is a polyoxygenated cyclic diterpenoid, mainly used to treat numerous cancers, including ovarian, breast, lung, cervical, and pancreatic cancer [2][3][4][5] . However, limited content (0.01-0.05 %) and localization of paclitaxel in specific organs (the bark of yew) renders production from natural sources low 3,6 .…”