Design and synthesis of threading intercalators to target DNA

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 23; pp. 6956 - 6959
• Main Authors: Howell, Lesley A., Gulam, Rosul, Mueller, Anja, O’Connell, Maria A., Searcey, Mark
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.12.2010; Elsevier
• Subjects: Acridine; Acridines - chemistry; Acridines - pharmacology; Animals; Antineoplastic agents; Antineoplastic Agents - chemistry; Antitumor activity; Biological and medical sciences; Cell Line, Tumor; DNA; DNA - antagonists & inhibitors; DNA - metabolism; Drug Design; General aspects; Humans; Intercalating Agents - chemical synthesis; Intercalating Agents - pharmacology; Intercalator; Medical sciences; Nucleic Acid Conformation; Pharmacology. Drug treatments; Intercalator; Acridine; DNA; Human; Promyelocytic leukemia; Intercalating agent; Peptides; Acridine derivatives; Cytotoxicity; In vitro; Biological activity; HL60 cell line; Octapeptide; Cell line; Carboxamide; Conjugated compound; Chemical synthesis; Tumor cell
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2010.09.128

Threading intercalators are high affinity DNA binding agents that bind by inserting a chromophore into the duplex and locating one group in each groove. The first threading intercalators that can be conjugated to acids, sulfonic acids and peptides to target them to duplex DNA are described, based upon the well studied acridine-3- or 4-carboxamides. Cellular uptake of the parent acridine is rapid and it can be visualized in the nucleus of cells. Both the parent compounds and their conjugates maintain antitumor activity.