Design, Synthesis, and Cytotoxicity of Novel 3-Arylidenones Derived from Alicyclic Ketones

Vijay Satam, Ravi K. Bandi, Ajaya K. Behera, Bijay K. Mishra, Samuel Tzou, Olivia Brockway, Balaji Babu, Matthias Zeller, Cara Westbrook, Susan L. Mooberry, Moses Lee, Hari Pati

Research output: Contribution to journalArticlepeer-review

Abstract

Forty-four novel chalcone-inspired analogs having a 3-aryl-2-propenoyl moiety derived from alicyclic ketones were designed, synthesized, and investigated for cytotoxicity against murine B16 and L1210 cancer cell lines. The analogs belong to four structurally divergent series, three of which (series g, h, and i) contain differently substituted cyclopentanone units and the fourth (series j) contains a 3,3-dimethyl-4-piperidinone moiety. Of these, the analogs in series j showed potential cytotoxic activity against murine B16 (melanoma) and L1210 (lymphoma) cells. The most active compounds 5j, 11j, 15j, and 12h produced IC 50 values from 4.4 to 15μm against both cell lines. A single-crystal X-ray structure analysis and molecular modeling studies confirmed that these chalcones have an E-geometry about the alkene bond and possess a slightly 'twisted' conformation similar to that of combretastatin A-4. At a concentration of 30μm, compounds 5j, 11j, and 15j did not cause microtubule depolymerization in cells, suggesting that they have a different mechanism of action. Forty-four novel chalcone-inspired analogs were designed and synthesized. Several compounds gave IC 50 values 4.4-15μm against the growth of L1210 and B16 murine cancer cells.

Original languageEnglish (US)
Pages (from-to)700-708
Number of pages9
JournalChemical Biology and Drug Design
Volume78
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • 3-aryl-2-propenoyl
  • Chalcones
  • Combretastatin A-4
  • Cyclopentanone
  • Cytotoxicity
  • Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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