Document Report Card

ID: ALA1148485

Journal: J Med Chem

Title: Synthesis and biological evaluation of new selective cytotoxic cyclolignans derived from podophyllotoxin.

Authors: Castro MA, Miguel del Corral JM, Gordaliza M, García PA, Gómez-Zurita MA, García-Grávalos MD, de la Iglesia-Vicente J, Gajate C, An F, Mollinedo F, San Feliciano A.

Abstract: Podophyllotoxin and some of its derivatives are cyclolignans currently used for removing warts and in the clinical treatment of malign neoplasms. As such, they have been an objective of the scientific community for decades, in the search for more potent and more selective anticancer agents. Our interest in the chemoinduction of drug selectivity led us to the design and preparation of new podophyllotoxin derivatives by reaction of podophyllic aldehyde with aliphatic, aromatic, and heteroaromatic amines. Several of the resulting imines displayed a significant selectivity against human colon carcinoma cells, even higher than that of the starting aldehyde. Additional biological studies indicate that these derivatives induce microtubule depolymerization, arrest cells at the G2/M phase of cell cycle, and are able to induce a delayed apoptosis after 48 h of treatment, characterized by caspase-3 activation.

CiteXplore: 14971901

DOI: 10.1021/jm030978h