Structure-Activity Relationship and in Vivo Anti-Tumor Evaluations of Dictyoceratin-A and -C, Hypoxia-Selective Growth Inhibitors from Marine Sponge

Marine Drugs

Yuji Sumii²  Naoyuki Kotoku¹  Akinori Fukuda²  Takashi Kawachi²  Masayoshi Arai²  Motomasa Kobayashi¹ 

[1] Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan

关键词: dictyoceratin-C;    dictyoceratin-A;    hypoxia-selective growth inhibitor;    marine sponge;    analog synthesis;    structure-activity relationship;    in vivo antitumor effect;   

DOI  :  10.3390/md13127074

来源: mdpi

【 摘 要 】

Oral dictyoceratin-C (1) and A (2), hypoxia-selective growth inhibitors, showed potent in vivo antitumor effects in mice subcutaneously inoculated with sarcoma S180 cells. Structurally modified analogs were synthesized to assess the structure–activity relationship of the natural compounds 1 and 2 isolated from a marine sponge. Biological evaluation of these analogs showed that the exo-olefin and hydroxyl and methyl ester moieties were important for the hypoxia-selective growth inhibitory activities of 1 and 2. Thus far, only substitution of the methyl ester with propargyl amide in 1 was found to be effective for the synthesis of probe molecules for target identification.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.