Suckling, Colin (2012) From multiply active natural product to candidate drug? Antibacterial (and other) minor groove binders for DNA. Future Medicinal Chemistry, 4 (8). pp. 971-989. ISSN 1756-8919Full text not available in this repository. Request a copy from the Strathclyde author
Natural products that bind to DNA in the minor groove are valuable templates for drug design. Examples include distamycin, netropsin, duocarmycin and anthramycin. Anticancer and anti-infective drugs feature strongly amongst their derivatives. The structures and activities of chemotypes with various therapeutic actions are discussed in the context of the broader field of therapeutically active minor groove binders. The evolution of a series of exceptionally potent and nontoxic antibacterial compounds is discussed using the general design principle of introducing additional hydrophobicity into the distamycin template to increase the strength of binding to DNA. As well as potent antibacterial compounds, antifungal and antiparasitic compounds with exceptional cellular activity against trypanosomes have been identified. Possible mechanisms of action including gene regulation and topoisomerase inhibition are discussed with the need in mind to understand selective toxicity in the series to support future drug discovery.
|Keywords:||gram positive bacteria, resistant staphylococcus aureus, substituted thiazole polyamide, pyrrole imidazole polyamides, inverted CCAAT BOX-2, sequence recognition, antitumor activity, plasmodium-falciparum, molecular recognition, Chemistry, Pharmacology, Molecular Medicine, Drug Discovery|
|Subjects:||Science > Chemistry|
|Department:||Faculty of Science > Pure and Applied Chemistry|
|Depositing user:||Pure Administrator|
|Date Deposited:||04 Jul 2012 09:06|
|Last modified:||22 Mar 2017 12:11|