Synthesis of 2-styrylchromones as a novel class of antiproliferative agents targeting carcinoma cells

• Published in: European journal of medicinal chemistry Vol. 44; no. 6; pp. 2552 - 2562
• Main Authors: Shaw, Arthur Y., Chang, Chun-Yi, Liau, Hao-Han, Lu, Pei-Jung, Chen, Hui-Ling, Yang, Chia-Ning, Li, Hao-Yi
• Format: Journal Article
• Language: English
• Published: PARIS Elsevier Masson SAS 01.06.2009; Elsevier
• Subjects: 2-Styrylchromone; Antineoplastic agents; Antiproliferation; Apoptosis - drug effects; Biological and medical sciences; Carcinoma cells; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry, Medicinal; Chromones - chemical synthesis; Chromones - classification; Chromones - pharmacology; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Fluorescent Antibody Technique; General aspects; HeLa Cells; Humans; Life Sciences & Biomedicine; Male; Medical sciences; Models, Molecular; Molecular Structure; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Quantitative Structure-Activity Relationship; Science & Technology; Stereoisomerism; Styrenes - chemical synthesis; Styrenes - classification; Styrenes - pharmacology; Time Factors; Antiproliferation; Carcinoma cells; 2-Styrylchromone; CHROMONES; HORMOTHAMNIONE; CLINICAL DEVELOPMENT; ANTICANCER AGENTS; CHEMISTRY; CONSTITUENTS; Antineoplastic agent; Carcinoma; Chromone derivatives; Cytotoxicity; Uterine cervix; Oxygen heterocycle; Modeling; Structure activity relation; Styrene derivatives; Molecular model; Bicyclic compound; Aromatic compound; Chemical synthesis; Antimitotic; Tumor cell; Human; Benzene derivatives; Prediction; Antitubulin; Malignant tumor; In vitro; Hela cell line; Three dimensional model; Cell line; Fluorine Organic compounds; Prostate; Cancer
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.01.034

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 μM 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 μM against HeLa cells. Flow cytometric analysis and DAPI staining revealed that HeLa cells exposed to 4q as low as 5 μM 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. [Display omitted] A series of 2-styrylchromone derivatives were synthesized and evaluated for their antiproliferative effects on a panel of carcinoma cells in this report.