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

Abstract

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.

• Authors: Yuji Sumii, Naoyuki Kotoku, Akinori Fukuda, Takashi Kawachi, Masayoshi Arai, Motomasa Kobayashi
• Journal: Marine drugs (Mar Drugs) Vol. 13 Issue 12 Pg. 7419-32 (Dec 16 2015) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 26694423 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Hydroxybenzoates
• Sesquiterpenes
• dictyoceratin-C
• smenospondiol

Topics

• Animals
• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Female
• Hydroxybenzoates (chemistry, isolation & purification, pharmacology)
• Mice
• Porifera (metabolism)
• Sarcoma 180 (drug therapy, pathology)
• Sesquiterpenes (chemistry, isolation & purification, pharmacology)
• Structure-Activity Relationship