Design, synthesis, and quantitative structure–activity relationship of cytotoxic γ-carboline derivatives

Three series of γ-carboline derivatives were designed and synthesized. All the compounds were tested for their cytotoxic activities in vitro against five human tumor cell lines (A549, SGC, HCT116, MCF-7, K562) and one multi-drug resistant subline (K562R). Most compounds showed moderate to potent cytotoxic activities against the tested cell lines. Sulfonate 11f exhibited more potent cytotoxic activities against almost all of the tested cells in comparison with the positive control, taxol, with IC50 values ranging from 0.15 to 4.5 μM. The structure–activity relationships were discussed and a statistically reliable QSAR model (r2 = 0.936, q2 = 0.581) was established by the CoMFA analysis performed using the cytotoxic data against K562 cell line as a template.

Three series of γ-carboline derivatives were designed, synthesized and tested for their cytotoxic activities in vitro against several human tumor cell lines. CoMFA analysis was carried out, and a statistically reliable QSAR model (r2 = 0.936, q2 = 0.581) was established.Figure optionsDownload as PowerPoint slide