ABSTRACT
Several acetyl derivatives of prenylnaphthohydroquinone have been synthetized and evaluated for their cytotoxicity against A-549 human lung carcinoma and H-116 human colon carcinoma neoplastic cells. The IC50 values against A-549 are compared with those observed for previously reported unsubstituted derivatives.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Hydroquinones/chemical synthesis , Hydroquinones/pharmacology , Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Hydroquinones/chemistry , Molecular Structure , Naphthoquinones/chemistry , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Podophyllotoxin/analogs & derivatives , Podophyllotoxin/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Imines/chemical synthesis , Imines/pharmacology , Mice , Podophyllotoxin/pharmacology , Structure-Activity RelationshipABSTRACT
Various Diels Alder cycloaddition conditions have been used to optimise the preparation of cytotoxic 6-alkyl-1, 4-naphthoquinones, which were subsequently transformed into 6(7)-alkyl-2-hydroxy-1, 4-naphthoquinones. The compounds thus prepared were evaluated for their cytotoxic activity against several neoplastic cultured cell lines and some of them showed IC50 values below the microM level.
