Structure-based hybridization, synthesis and biological evaluation of novel tetracyclic heterocyclic azathioxanthone analogues as potential antitumor agents

• Published in: European journal of medicinal chemistry Vol. 103; pp. 615 - 627
• Main Authors: Chen, Tsung-Chih, Wu, Chia-Lun, Lee, Chia-Chung, Chen, Chun-Liang, Yu, Dah-Shyong, Huang, Hsu-Shan
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 20.10.2015; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Azathioxanthones; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Medicinal; Cytostatic and cytotoxic activities; DNA Topoisomerases, Type I - metabolism; DNA Topoisomerases, Type II - metabolism; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Life Sciences & Biomedicine; Molecular Structure; MTT assay; NCI-60 human tumor cell lines; Pharmacology & Pharmacy; Quinolines - chemistry; Quinolines - pharmacology; Science & Technology; Structure-Activity Relationship; Thioxanthenes - chemistry; Thioxanthenes - pharmacology; Topoisomerase assays; Topoisomerase I Inhibitors - chemical synthesis; Topoisomerase I Inhibitors - chemistry; Topoisomerase I Inhibitors - pharmacology; Topoisomerase II Inhibitors - chemical synthesis; Topoisomerase II Inhibitors - chemistry; Topoisomerase II Inhibitors - pharmacology; Azathioxanthones; Cytostatic and cytotoxic activities; MTT assay; Topoisomerase assays; NCI-60 human tumor cell lines; RAPID COLORIMETRIC ASSAY; ANTHRACENE-9,10-DIONES; DOXORUBICIN; PIXANTRONE; MOLECULAR TARGET; DNA TOPOISOMERASES; TOPOISOMERASE-I INHIBITORS; ANTICANCER DRUG SCREEN; DERIVATIVES; STRUCTURE-BASED DESIGN
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.09.050

A series of tetracyclic heterocyclic azathioxanthones were synthesized and evaluated for cell proliferations, topoisomerase inhibitions, and NCI-60 cell panel assay, respectively. Compounds 5, 7, 8, 16, and 19 were selected for topoisomerase assay after MTT assay. 7 not only showed cytotoxic effect (IC50 = 2.84 ± 0.64 μM) in PC-3 cells but also revealed topoisomerases inhibition with IC50 (10–25 μM) and increased apoptotic cleavage of PARP and caspase 3 activity. The overall of novel azathioxanthones with different cytostatic and cytotoxic activities should be further developed as new potential candidates for anticancer drugs. [Display omitted] •A series of novel tetracyclic heterocyclic azathioxanthones were synthesized.•Ten compounds were selected and tested by NCI against their anticancer potency.•Compound 7 revealed topoisomerase I and II inhibition in drug screening assays.