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Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
Published on: January 20, 2016
Chemistry of DNA minor groove binding agents
Gul Shahzada Khan1, Afzal Shah, Zia-ur-Rehman
1Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Abstract:
Most of the clinically used anticancer drugs exert their antitumor effect by damaging the replication machinery of DNA either by covalent or non-covalent binding. Intercalation and groove fitting are the major modes of non-covalent interaction. Small crescent shaped molecules have been claimed to bind with DNA via minor grooves. A plethora of hybrid molecules based on distamycin or netropsin have been synthesised with the objectives of improved selectivity and specificity with no/reduced unwanted side effects. This review critically and objectively describes the previously known hybrid DNA minor groove binding agents based on five membered, distamycin or netropsin. Moreover, the future use of six-membered benzamides has also been highlighted. Special emphasis has been put on developing structure-activity relationships of DNA minor groove binding agents.
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