title: The synthesis and biological evaluation of new DNA-directed alkylating agents, phenyl N-mustard-4-anilinoquinoline conjugates containing a urea linker.
abstract: We synthesized a series of phenyl N-mustard-4-anilinoquinoline conjugates to study their antitumorigenic effects. These agents were prepared by the condensation of 4-[N,N-bis(2-chloroethyl)amino]phenyl isocyanate with 6-amino-4-methylamino or 4-anilinoquinolines. The structure-activity relationship (SAR) studies revealed that the C2-methylquinoline derivatives (18a-o) were generally more cytotoxic than the C2-phenylquinoline conjugates (23a-d) in inhibiting the cell growth of various human tumor cell lines in vitro. However, the methylamino or aniline substituents at C4 of quinoline did not influence the cytotoxic effects. The title conjugates were capable of inducing DNA cross-linking and promoting cell-cycle arrest at the G2/M phase. This study demonstrates that phenyl N-mustard-4-anilinoquinoline conjugates are generally more potent than phenyl N-mustard-4-anilinoquinazoline conjugates against the cell growth of various tumor cell-lines.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India.
authors.forename: Bhavin
authors.initials: B
authors.lastname: Marvania
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kakadiya
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India.
authors.forename: Wilson
authors.initials: W
authors.lastname: Christian
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Tai-Lin
authors.initials: TL
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Sharda
authors.initials: S
authors.lastname: Suman
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Kiran
authors.initials: K
authors.lastname: Tala
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan. Electronic address: bmtcl@ibms.sinica.edu.tw.
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India.
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan. Electronic address: tlsu@ibms.sinica.edu.tw.
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Su
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D006801:Humans; D011804:Quinolines / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011804:Quinolines; D014508:Urea; D004247:DNA; C037219:quinoline
keywords: Apoptosis; Cell cycle; DNA cross-linking; DNA-directed alkylating agents; Phenyl N-mustard; Quinolines