Novel substituted ( Z)-5-(( N-benzyl-1 H-indol-3-yl)methylene)imidazolidine-2,4-diones and 5-(( N-benzyl-1 H-indol-3-yl)methylene)pyrimidine-2,4,6(1 H,3 H,5 H)-triones as potent radio-sensitizing agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 2; pp. 600 - 602
• Main Authors: Reddy, Y. Thirupathi, Sekhar, Konjeti R., Sasi, Nidhish, Reddy, P. Narsimha, Freeman, Michael L., Crooks, Peter A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.01.2010; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Aplysinopsin analogs; Barbiturates - chemical synthesis; Barbiturates - chemistry; Barbiturates - toxicity; Benzene - chemistry; Biological and medical sciences; HT29 Cells; Humans; Indoles - chemical synthesis; Indoles - chemistry; Indoles - toxicity; Indolyl barbiturates; Indolyl hydantoins; Medical sciences; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - toxicity; Radiation therapy and radiosensitizing agent; Radiation-Sensitizing Agents - chemical synthesis; Radiation-Sensitizing Agents - chemistry; Radiation-Sensitizing Agents - toxicity; Radiosensitizing agents; Treatment with physical agents; Treatment. General aspects; Tumors; Indolyl barbiturates; Aplysinopsin analogs; Indolyl hydantoins; Radiosensitizing agents; Human; Nitrile; Benzene derivatives; Hydantoins; In vitro; Biological activity; Alkaloid; Cell line; Radiosensitizing agent; Pyrimidine derivatives; Benzonitrile derivatives; Colon; Barbiturates; Indole derivatives; Chemical synthesis; Tumor cell
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.11.082

A series of ( Z)-5-(( N-benzyl-1 H-indol-3-yl)methylene)imidazolidine-2,4-dione ( 9a– 9m) and 5-(( N-benzyl-1 H-indol-3-yl)methylene)-pyrimidine-2,4,6(1 H,3 H,5 H)-trione ( 10a–10i) derivatives that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized. These analogs were evaluated for their radiosensitization activity against the HT-29 cell line. Three analogs, 10a, 10b, and 10c, were identified as the most potent radio-sensitizing agents. A series of ( Z)-5-(( N-benzyl-1 H-indol-3-yl)methylene)imidazolidine-2,4-dione ( 9a– 9m) and 5-(( N-benzyl-1 H-indol-3-yl)methylene)pyrimidine-2,4,6(1 H,3 H,5 H)-trione ( 10a– 10i) derivatives that incorporate a variety of aromatic substituents in both the indole and N-benzyl moieties have been synthesized. These analogs were evaluated for their radiosensitization activity against the HT-29 cell line. Three analogs, 10a, 10b, and 10c were identified as the most potent radiosensitizing agents.