Aplysinopsin analogs: Synthesis and anti-proliferative activity of substituted ( Z)-5-( N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones

• Published in: Bioorganic & medicinal chemistry 2010-05, Vol.18 (10), p.3570-3574
• Main Authors: Thirupathi Reddy, Y., Narsimha Reddy, P., Koduru, Srinivas, Damodaran, Chendil, Crooks, Peter A.
• Format: Article
• Language: English
• Subjects: Animals; Anti-proliferative activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Aplysinopsin analogs; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Drug Design; Drug Screening Assays, Antitumor - methods; Humans; Imidazolidines - chemical synthesis; Imidazolidines - pharmacology; Indole derivatives; Indoles - chemistry; Inhibitory Concentration 50; Microwave irradiation; Structure-Activity Relationship; Tryptophan - analogs & derivatives; Tryptophan - chemical synthesis; Tryptophan - chemistry; Tryptophan - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.03.054

A series of substituted ( Z)-5-( N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione ( 3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods. These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC 50 values of 4.4 and 5.2 μM, respectively, compared to 5-fluorouracil (IC 50 = 15.2 μM) against MCF-7 cells. A series of substituted ( Z)-5-( N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione ( 3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC 50 values of 4.4 and 5.2 μM, respectively, compared to 5-fluorouracil (IC 50 = 15.2 μM) against MCF-7 cells.