Synthesis and Anticancer Activity Evaluation of Novel Phenanthridine Derivatives

Conclusions Based on the structure of sanguinarine, fourteen phenanthridine derivatives 8a-m were synthesized and evaluated for their cytotoxic activity against five different human cancer cell lines. Among the evaluated compounds, 8a exhibited a broad spectrum of anti-proliferative activities against all the tested cancer cell lines. Further mechanistic assay revealed that compound 8a could inhibit the activity of both DNA Top I and Top II, as well as preventing cell transition from S to G2 phase dose-dependently. Apoptosis studies against MCF-7 cells indicated that downregulation of Bcl-2 and upregulation of Bax expression may contribute to the anti-proliferative activities. In summary, these findings suggest that molecule 8a is a potent lead compound in the derived phenanthridine derivatives. Further molecule 8a based structural modification may be beneficial in the discovery of novel anticancer agents with improved antitumor activity and reduced side effects. Materials and Methods Chemistry All chemicals were obtained from commercial suppliers and used without further purification. Reactions progress was detected by thin layer chromatography (TLC) and visualized under UV light. Two hundred to three hundred mesh silica gel was used for column chromatography. All compounds were characterized by 13C NMR, 1H NMR, and HRMS. 1H and 13C NMR spectra were recorded on Mercury Plus-400 with internal standard used TMS and recorded in parts per million (ppm). Date were reported as...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research