Design, synthesis, and quantitative structure-activity relationship of cytotoxic gamma-carboline derivatives.
Three series of gamma-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 IC(50) values ranging from 0.15 to 4.5 microM. The structure-activity relationships were discussed and a statistically reliable QSAR model (r(2)=0.936, q(2)=0.581) was established by the CoMFA analysis performed using the cytotoxic data against K562 cell line as a template.
Chen
Jing
J
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Dong
Xiaowu
X
Liu
Tao
T
Lou
Jianshu
J
Jiang
Chaoyi
C
Huang
Wenhai
W
He
Qiaojun
Q
Yang
Bo
B
Hu
Yongzhou
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D020014:K562 Cells; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
D000970:Antineoplastic Agents; D002243:Carbolines; C055572:gamma-carboline