title: Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent antitumor agents.
abstract: Novel kazusamycin A derivatives were designed in the viewpoint of decrease of reactivity at the alpha,beta-unsaturated delta-lactone moiety against Michael-type addition. Although 25-30 steps were required for the synthesis of each compound, their syntheses were achieved. Cytotoxicity against HPAC cell line was evaluated, and two of them exhibited comparable potency to kazusamycin A. Hepatic toxicity of these designed compounds was much lower than that of kazusamycin A.
authors.affiliation: Discovery Technology Laboratory II, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Ando.Ryoichi@mk.m-pharma.co.jp
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ando
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Amano
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakamura
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Arai
authors.forename: Isao
authors.initials: I
authors.lastname: Kuwajima
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; C042541:kazusamycin A