ABSTRACT
Several new prenylnaphthohydroquinone derivatives have been prepared through the Diels-Alder condensation between alpha-myrcene and 1,2-benzoquinone and evaluated for their cytotoxic activity against A-549, HT-29 and MB-231 cultured cell lines. All of them have shown GI50 values in the microM level.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Naphthoquinones/chemistry , Naphthoquinones/toxicity , Prenylamine/analogs & derivatives , Cell Line, Tumor , Cell Survival/drug effects , Humans , Inhibitory Concentration 50 , Isomerism , Molecular Structure , Naphthoquinones/chemical synthesis , Prenylamine/chemical synthesis , Prenylamine/chemistry , Prenylamine/toxicityABSTRACT
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.
