Design, Synthesis and Cytotoxicity of Novel Chalcone Analogs Derived From 1-Cyclohexylpyrrolidin-2-one and 2,3-Dihydrobenzo[f]chromen-1-one

Document Type

Article

Publication Date

5-2012

Publication Source

Archiv der Pharmazie

Volume Number

345

Issue Number

5

First Page

341

Last Page

348

Publisher

Wiley-V C H Verlag, GmbH

ISSN

0365-6233

Comments

The authors thank Conjura Pharmaceuticals, LLC for support. Support from the Department ofChemistry, Sambalpur University for providing facilities for research is also acknowledged. The X-ray diffractometer at Youngstown State University was funded by NSF Grant 0087210, Ohio Board of Regents Grant CAP-491, and by Youngstown State University. Support from the President's Council Excellence award is acknowledged (SLM).

Abstract

Two divergent series of novel chalcone analogs, one derived from 1-cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC50 values between the range of 5 and 6?mu M. With an IC50 value of 3.4?mu M, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the beta-hydroxy ketone product (4a) and the a,beta-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the beta-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond.

Keywords

Benzochromanone, Chalcones, Cytotoxicity, Tubulin, X-ray, Derivatives, Inhibitors, Growth

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