title: Effect of the diamine nonleaving group in platinum-acridinylthiourea conjugates on DNA damage and cytotoxicity.
abstract: The following complexes of type [PtCl(R)(ACRAMTU)](NO3)2 (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea)), derived from prototype 1 (with R = ethane-1,2-diamine), were synthesized: 2 (with R = (1R,2R)-1,2-diaminocyclohexane), 3 (with R = propane-1,3-diamine), 4 (with R = N1,N1,N2,N2-tetramethylethane-1,2-diamine), and 5 (with R = 2,2'-bipyridine). The DNA sequence specificity of the conjugates and their antiproliferative potential in HL-60 and H460 cells were investigated. Conjugate 3 showed the strongest non-cisplatin-type DNA damage in polymerase stop assays and superior cell kill efficacy in H460 lung cancer (IC50 = 70 nM).
authors.affiliation: Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
authors.forename: Rajsekhar
authors.initials: R
authors.lastname: Guddneppanavar
authors.forename: Jayati Roy
authors.initials: JR
authors.lastname: Choudhury
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Kheradi
authors.forename: Bartlett D
authors.initials: BD
authors.lastname: Steen
authors.forename: Gilda
authors.initials: G
authors.lastname: Saluta
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kucera
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Day
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bierbach
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008969:Molecular Sequence Data; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C520650:chloro(1-(2-(acridin-9-ylamino)ethyl)-1,3-dimethylthiourea)(propane-1,3-diamine)platinum(II); D013890:Thiourea; D002945:Cisplatin