Synthesis of 2-styrylchromones as a novel class of antiproliferative agents targeting carcinoma cells.
A series of 2-styrylchromone analogs were synthesized and examined for their antiproliferative effects on a panel of carcinoma cells. Among the tested agents, only 4m exhibited a moderate activity with an IC(50) value of 28.9 microM against PC-3 cells which indicates the selectivity of PC-3 cells in response to 2-styrylchromones. In addition, 4q demonstrated the most antiproliferative effect with an IC(50) value of 4.9 microM against HeLa cells. Flow cytometric analysis and DAPI staining revealed that HeLa cells exposed to 4q as low as 5 microM induced cell death through sub-G1 arrest and DNA fragmentation. Furthermore, CoMFA analysis of tested 2-styrylchromones resulted in a q(2) of 0.459 to generate a 3D-QSAR model on BT483 cell line. Together, these results suggest a potential structural optimization and pharmacological study of 2-styrylchromones.
Shaw
Arthur Y
AY
Department of Chemistry, Tamkang University, Tamsui 251, Taiwan. shaw299@mail.tku.edu.tw
Chang
Chun-Yi
CY
Liau
Hao-Han
HH
Lu
Pei-Jung
PJ
Chen
Hui-Ling
HL
Yang
Chia-Ning
CN
Li
Hao-Yi
HY
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D013343:Styrenes / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*; D013997:Time Factors
D002867:Chromones; D013343:Styrenes