ABSTRACT
A variant structural skeleton of epipodophyllotoxin was synthesized and found to rival the natural cyclolignan in antiproliferative and microtubule destabilizing properties. This discovery leads to a new structural class of tubulin targeting agents.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Podophyllotoxin/pharmacology , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Crystallography, X-Ray , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Jurkat Cells , MCF-7 Cells , Models, Molecular , Molecular Structure , Podophyllotoxin/chemical synthesis , Podophyllotoxin/chemistryABSTRACT
4H-Pyrano-[2,3-b]naphthoquinone is a structural motif commonly found in natural products manifesting anticancer activities. As part of a program aimed at structural simplification of bioactive natural products utilizing multicomponent synthetic processes, we developed a compound library based on this heterocyclic scaffold. We found that several library members displayed low micromolar antiproliferative activity and induced apoptosis in human cancer cells. Selected compounds showed promising activity against cancer cell lines resistant to proapoptotic stimuli, demonstrating their potential in treating cancers with dismal prognoses.