title: Synthesis and structure-activity relationships of potential anticancer agents: alkylcarbamates of 3-(9-acridinylamino)-5-hydroxymethylaniline.
abstract: A series of potential 9-anilinoacridine antitumor agents, 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) derivatives with monosubstituent at C4' and disubstituents at C4' and C5' of the acridine ring and their alkylcarbamates, were synthesized for evaluation of their antitumor activity. A structure-activity relationship (SAR) study showed that the AHMA-alkylcarbamates were more potent than their corresponding parent AHMA compounds. In addition, the cytotoxicity of the AHMA-alkylcarbamate decreased with increasing length and size of the alkyl function. Among these compounds, AHMA-ethylcarbamate (18) and 4'-methyl-5'-dimethylaminoethylcarboxamido-AHMA-ethylcarb amate (34) possess potent cytotoxicity on the inhibition of human leukemic HL-60 cell growth in culture. Further in vivo studies of these compounds displayed significant anticancer therapeutic effects in mice bearing sarcoma 180, Lewis lung carcinoma, and P388 leukemia.
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, R.O.C. tlsu@ibms.sinica.edu.tw
authors.forename: T L
authors.initials: TL
authors.lastname: Su
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: L F
authors.initials: LF
authors.lastname: Huang
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: M K
authors.initials: MK
authors.lastname: Basu
authors.forename: X G
authors.initials: XG
authors.lastname: Zhang
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship
chemical_list: C401318:3-(9-acridinylamino)-5-hydroxymethylaniline ethylcarbamate; D000166:Acridines; D000970:Antineoplastic Agents; D002219:Carbamates