Unsymmetrical methylene derivatives of indoles as antiproliferative agents.
Indole-3-carbinol is a natural product which has been shown to reduce the incidence of spontaneous and carcinogen-induced mammary tumours in animals. Eighteen unsymmetrical methylene derivatives of indoles were prepared by reaction of Mannich bases of 7-hydroxycoumarins with substituted indoles in acetic or propionic anhydride. The synthesised molecules were tested in vitro against the MCF7 and MDA-MB-231 breast cancer cell lines by MTT and cell count assays. Results from 16 tested compounds showed that 60% of them exerted some effects against the MDA-MB-231 compared to about 30% towards the MCF7. Among all, the 3-(7'-acetoxy-4-methylcoumarin-8'-yl)methyl-2-methylindole resulted the most effective in both cell lines, compared to indole-3-carbinol. In conclusion, these preliminary results report that some of these compounds might be promising potential antiproliferative agents.
Mazzei
M
M
Department of Pharmaceutical Sciences, Viale Benedetto XV 3, 16132 Genova, Italy. mazzei@cba.unige.it
Miele
M
M
Nieddu
E
E
Barbieri
F
F
Bruzzo
C
C
Alama
A
A
D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C450185:3-(7'-acetoxy-4-methylcoumarin-8'-yl)methyl-2-methylindole; D000970:Antineoplastic Agents; D003374:Coumarins; D007211:Indoles