title: The in vitro antitumor assay of "half-mustard type" phenothiazines in screens of AIDS-related leukemia and lymphomas.
abstract: Twelve different "half-mustard type" phenothiazines were newly synthesized and tested on seven AIDS-related lymphoma (ARL) tumor cell lines, one leukemia CCRF-CEM cell culture and five different lymphoma lines; RL, KD-488, AS283, PA682 and SU-DHL-7 cell lines. The alkylene-urea substituted phenothiazines affected the growth and inhibited the growth rate of AIDS-related lymphoma cells. The Cl-substituent at the 2-position was more effective than the CF3 substitution. In AIDS-related leukemia also the compounds with Cl at the 2-position with propylene or butylene linkers, -(CH2)3- and -(CH2)4-, respectively, were more effective than the CF3 substituted compounds. Two of the six phenothiazine-substituted alkyl-urea derivatives, i.e., 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)propyl-l-urea (9, GI50 = -5.66, TGI = -5.04) and 1-(2-chloroethyl)- 3-(2-chloro-10H-phenothiazin-10-yl)butyl-1-urea (10, GI50 = -5.61, TGI = -5.12) exhibited antitumor activity for AIDS-related leukemia and five AIDS-related lymphomas. The trifluoromethyl-substituted derivatives were not as effective on AIDS-related tumor cell lines. Apparently, the substituent at the 2-position on the phenothiazine and the alkylene number of the linker attached to the nitrogen of the phenothiazine ring have an important role in the compound's antitumor effects on AIDS-related leukemia and lymphomas.
authors.affiliation: SCRIPTGEN Pharmaceuticals, Inc., Medford, MA 02155, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Wuonola
authors.forename: M G
authors.initials: MG
authors.lastname: Palfreyman
authors.forename: N
authors.initials: N
authors.lastname: Motohashi
authors.forename: M
authors.initials: M
authors.lastname: Kawase
authors.forename: S
authors.initials: S
authors.lastname: Gabay
authors.forename: J
authors.initials: J
authors.lastname: Molnár
mesh_terms: D000970:Antineoplastic Agents; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology*; D010797:Phthalimides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D010640:Phenothiazines; D010797:Phthalimides; D014508:Urea