Synthesis and in vitro screening of novel N-benzyl aplysinopsin analogs as potential anticancer agents |
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Authors: | Penthala Narsimha Reddy Yerramreddy Thirupathi Reddy Crooks Peter A |
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Institution: | Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA |
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Abstract: | A series of novel substituted (Z)-5-((1-benzyl-1H-indol-3-yl)methylene)imidazolidin-2,4-diones (3a-f) and (Z)-5-((1-benzyl-1H-indol-3-yl)methylene)-2-iminothiazolidin-4-ones (3g-o) have been synthesized utilizing microwave irradiation. These analogs were evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines. Compound 3i exhibits potent growth inhibition against melanoma UACC-257 (GI50 = 13.3 nM) and OVCAR-8 ovarian (GI50 = 19.5 nM) cancer cells while possessing significant cytotoxicity (LC50 = 308 nM and LC50 = 851 nM, respectively) against the same cell lines within this series of compounds. A second analog, 3a, had GI50 values of 307 and 557 nM against SK-MEL-2 melanoma and A498 renal cancer cell lines, and exhibited GI50 values ranging from 0.30 to 6 μM against 98% of all cancer cell lines in the 60-cell panel. Thus, (Z)-5-((5-chloro-1-(4-fluorobenzyl)-1H-indol-3-yl)methylene)-2-iminothiazolidin-4-one (3i) and (Z)-methyl 1-(4-cyanobenzyl)-3-((2,5-dioxoimidazolidin-4-ylidene)methyl)-1H-indole-6-carboxylate (3a) can be regarded as useful lead compounds for further structural optimization as antitumor agents. |
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Keywords: | N-Benzyl indole-3-carboxaldehydes Hydantoin 2-Imino thiazolidin-4-one In vitro cytotoxicity |
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