ABSTRACT
A series of novel γ-(triazolyl ethylidene)butenolides (4-23) were prepared from commercially available l-ascorbic acid in good yields. These butenolides on reaction with ethanolic ammonia/amines led to formation of respective 5-hydroxy pyrrolinones (24-33). The two of these pyrrolinones on dehydration with p-toluenesulfonic acid, were transformed into γ-(triazolyl ethylidene)pyrrolinones (34, 35). Among all the newly synthesized hybrid molecules tested for anticancer activity in vitro, compounds 24, 25, 26, 27, 28, 30 and 32 showed significant activity against MCF-7, MDA-MB-231, PC-3 or U-937 cells. In particular compound 25 (IC50 = 11.3 µM) exhibited most potent activity against breast cancer cells and preliminary studies revealed that potency of this compound is due to ROS generation, subsequent activation of p38, leading to apoptosis and inhibition of cancer cells.
Subject(s)
4-Butyrolactone/pharmacology , Antineoplastic Agents/pharmacology , Pyrrolidinones/pharmacology , Triazoles/pharmacology , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HCT116 Cells , HEK293 Cells , Humans , MCF-7 Cells , Molecular Structure , Pyrrolidinones/chemical synthesis , Pyrrolidinones/chemistry , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistryABSTRACT
A series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1H-azoles has been identified as potent antitubercular agents against Mycobacterium tuberculosis. Synthesis of compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl cyclopropyl methanols followed by nucleophilic attack of the azoles on the carbocation intermediates. Several of the compounds 26, 34, and 36 exhibited significant antitubercular activities with MIC value as low as 1.56, 1.56, and 0.61 µg/mL, respectively, comparable to many standard drugs. These compounds were also screened against other strains of bacteria and fungi, and few of them showed good antifungal activity against A. fumigatus, responsible for lung infection.
