Enediyne compounds - new promises in anticancer therapy.
Scientists of all kinds have long been intrigued by the nature, action and potential of natural toxins that possess exceptional antibacterial and anticancer activities. These compounds, named enediynes, are among the most effective chemotherapeutic agents known. Often compared with intelligent weapons, due to the unique structure and sophisticated mechanism by which they destroy double-helical DNA, enediyne antibiotics are nowadays the most promising leaders in the anticancer therapy. Apart from their diversity, enediyne compounds share some structural and functional similarities. One fragment of a structure is responsible for the recognition and transport, another part acts as molecular trigger while the third, reactive enediyne unit, undergoes Bergman cycloaromatization and causes DNA breakage. Members of the enediyne family are already in clinical use to treat various cancers, but more general use is limited by their complex structure, which makes them formidable targets for synthetic chemists. There are three main approaches in the design of new enediyne-related compounds: improvement of enediyne >>warheads<<, increasing the selectivity and control of chemical or photo-induced activation. This paper gives an overview of naturally occurring enediynes, their mode of action and efforts undertaken to design artificial enediyne-related DNA cleaving agents.
Gredicak
Matija
M
Ruder Bosković Institute, Division of Organic Chemistry and Biochemistry,10002 Zagreb, Croatia.
Jerić
Ivanka
I
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D053281:Enediynes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D053281:Enediynes