Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent antitumor agents

Ryoichi Ando; Yusaku Amano; Hideo Nakamura; Noriyoshi Arai; Isao Kuwajima

doi:10.1016/j.bmcl.2006.03.056

Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent antitumor agents

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3315-8. doi: 10.1016/j.bmcl.2006.03.056. Epub 2006 Apr 17.

Authors

Ryoichi Ando¹, Yusaku Amano, Hideo Nakamura, Noriyoshi Arai, Isao Kuwajima

Affiliation

¹ Discovery Technology Laboratory II, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. [email protected]

PMID: 16617017
DOI: 10.1016/j.bmcl.2006.03.056

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.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / toxicity
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Design*
Fatty Acids, Unsaturated / chemical synthesis
Fatty Acids, Unsaturated / chemistry
Fatty Acids, Unsaturated / pharmacology
Fatty Acids, Unsaturated / toxicity
Humans
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents
Fatty Acids, Unsaturated
kazusamycin A