Synthesis and antitumor activity of indolylpyrimidines: marine natural product meridianin D analogues.
Marine indole alkaloid meridianin D analogues have been synthesized starting from the appropriate 3-cyanoacetyl indole. A facile two-step conversion of 3-cyanoacetyl indole to the corresponding cyano meridianin D analogue by treatment with dimethylformamide-dimethylacetal and further cyclization of the resulting enaminonitrile with aminoguanidine is described. Then, alkaline hydrolysis of cyano meridianin D afforded the carboxylic acid analogue. The treatment of acid with 75% H(2)SO(4) afforded the desired 6-debromomeridianin D. Simply treatment of cyano meridianin D analogue with hydrazine hydrate afforded the amidrazone analogue. The biological evaluation indicated that cyano analogue showed good cytotoxic activity with IC(50) values of 0.85 and 2.65microg (against MCF7 and HeLa, respectively), but acid and amidrazone analogues showed high cytotoxicity with IC(50) values of 0.75 and 0.25microg, respectively (against MCF7).
Radwan
Mohamed A A
MA
Applied Organic Chemistry Department, National Research Centre, Dokki, Giza, Egypt. m1radwan@yahoo.com
El-Sherbiny
Mahmoud
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001688:Biological Products; D007211:Indoles; D011743:Pyrimidines; C030374:indole