Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent antitumor agents.
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.
Ando
Ryoichi
R
Discovery Technology Laboratory II, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Ando.Ryoichi@mk.m-pharma.co.jp
Amano
Yusaku
Y
Nakamura
Hideo
H
Arai
Noriyoshi
N
Kuwajima
Isao
I
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
D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; C042541:kazusamycin A