title: Cell differentiation enhancement by hydrophilic derivatives of 4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-diones in HL-60 leukemia cells.
abstract: Among five carboxamide derivatives (13-17), N-(2-dimethylaminoethyl)-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione-2-carboxamide (13) showed the greatest enhancement of all-trans retinoid acid (ATRA)-induced differentiation in HL-60 cells, inducing nearly complete differentiation at a concentration of 0.02microM. On the other hand, 2-hydroxymethyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione (2) and 2-(1-hydroxylethyl)-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione (18) exhibited excellent and equally potent differentiation effects on HL-60 cells. To improve their water solubility, ester-type hydrophilic prodrugs (23-26) were also synthesized. Compounds 13 and 23-26 are identified in this paper as new anti-leukemic drug candidates.
authors.affiliation: Pharmaceutical Technology Division, Biomedical Engineering Center, Industrial Technology Research Institute, No. 321, Kuang Fu Road, Section 2, Hsinchu, Taiwan.
authors.forename: Yen-Fang
authors.initials: YF
authors.lastname: Wen
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Pi-Tsan
authors.initials: PT
authors.lastname: Huang
authors.forename: Mei-Hwai
authors.initials: MH
authors.lastname: Chen
authors.forename: Wuu-Chian
authors.initials: WC
authors.lastname: Shin
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Hsu
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007938:Leukemia / Q000473:pathology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D013876:Thiophenes