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.

Marine natural products

“…772 and 773) were synthesised for the rst time. Meroterpenoids that had initial total syntheses are panicein A 2 , 774,775 dictyoceratins A 776 and C, [777][778][779] and neopetrosiquinones A and B. 780,781 The structure of siphondictyal B 782 has been revised to 1112, based upon total synthesis.…”

Retracted Article: The synthesis and biological activity of marine alkaloid derivatives and analogues

“…Cancer is one of the major diseases that seriously endanger human health in today's society. [139][140][141][142][143] In the treatment of cancer, there are mainly surgical treatment, chemotherapy, radiotherapy and other means, among which chemotherapy is the most important treatment method currently used. [144][145][146][147] The research and development of novel compounds with a unique chemical structure has become an important research direction in the eld of anti-cancer drugs.…”

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds

“…Other promising chemicals derived from sponges with potential use in humans are the compounds Dictyoceratin-A and -C isolated from the Indonesian marine sponge Dactylospongia elegans. These two sesquiterpene phenols inhibited the growth of murine sarcoma 180 tumors by 90% after being orally administrated at the dose of 50 mg/Kg every two days for two weeks [70]. Additionally, the sphingolipid-like semi-synthetic compound Rizochalinin, a derivative from Rhizochalin, a bioactive chemical isolated from the marine sponge Rhizochalina incrustata, apart from inducing potent cytotoxicity with an IC 50 in the low micromolar range in human prostate cancer cells, also impaired in vivo tumor growth of human prostate PC-3 and 22Rv1 xenografts by 27% and 46.8% respectively, after being i.p.…”