Synthesis and anti-cancer activity of 2-alkylaminomethyl- 5-( E)-alkylidene cyclopentanone hydrochlorides

• Published in: Bioorganic & medicinal chemistry 1994-10, Vol.2 (10), p.1091-1097
• Main Authors: Chen, Haitao, Ji, Zhizhong, Wong, Lan K., Siuda, Jerome F., Narayanan, Ven L.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Cyclopentanes - chemical synthesis; Cyclopentanes - pharmacology; Drug Screening Assays, Antitumor; Magnetic Resonance Spectroscopy; Tumor Cells, Cultured
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(00)82059-3

A series of 2-alkylaminomethyl-5-( E)-alkylidene cyclopentanone hydrochlorides ( 2), have been synthesized and evaluated as anti-cancer agents. These compounds were designed as masked α-methylenecyclopentanones, which appear in many cytotoxic or anti- cancer natural products. Most of the synthesized compounds were found to be active towards various human cancer cell lines and many showed significant subpanel selectivity. For compounds containing the same alkylidene moiety (from C 3 to C 9), the dimethylamino- methyl analogs were more active than structures possessing morpholino-, pyrrolidino-, or piperidino-methyl groups. Alteration of the alkylidene moiety had little effect on anti-cancer potency. The mass spectrum of a glutathione adduct of 2h indicated that the mechanism of action for these anti-cancer agents may be related to the attack at the aminomethyl carbon atom by biological nucleophilic thiols. Alkylidene cyclopentanone Mannich bases, 2 were synthesized as masked analogs of α-methylenecyclopentanone. Most of the substances were found to be active toward various human cell cancer lines.