Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies.
Echinomycin is the prototypical bisintercalator, a molecule that binds to DNA by inserting two planar chromophores between the base-pairs of duplex DNA, placing its cyclic depsipeptide backbone in the minor groove. As such, it has been the focus of an extensive number of investigations into its biological activity, nucleic acid binding and, to some extent, its structure-activity relationships. However, echinomycin is also the parent member of an extended family of natural products that interact with DNA by a similar mechanism of bisintercalation. The structural variety in these compounds leads to changes in sequence selectivity and and biological activity, particularly as anti-tumour and anti-viral agents. One of the more recently identified marine natural products that is moving close to clinical development is thiocoraline, and it therefore seems timely to review the various bisintercalator natural products.
Dawson
Simon
S
Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Malkinson
John P
JP
Paumier
David
D
Searcey
Mark
M
D001688:Biological Products; D004247:DNA / Q000378:metabolism; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004448:Echinomycin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007364:Intercalating Agents; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011810:Quinoxalines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D001688:Biological Products; D004247:DNA; D047630:Depsipeptides; D004448:Echinomycin; D007364:Intercalating Agents; D010455:Peptides; D010456:Peptides, Cyclic; D011804:Quinolines; D011810:Quinoxalines; C099304:quinoxapeptin A; C109005:thiocoraline; C063090:sandramycin; C031945:triostin A; C086645:BE 22179; C029831:luzopeptins