Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1-cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one

Kimberly A. Brien, Ravi Kumar Bandi, Ajaya Kumar Behera, Bijay Kumar Mishra, Poulomi Majumdar, Vijay Satam, Mia Savagian, Samuel Tzou, Megan Lee, Matthias Zeller, Andrew J. Robles, Susan Mooberry, Hari Pati, Moses Lee

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 IC 50 values between the range of 5 and 6μM. With an IC 50 value of 3.4μM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the β-hydroxy ketone product (4a) and the α,β-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the β-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. Twenty-four chalcone analogs and one aldol product derived from 1-benzo[f]chromanone and N-cyclohexylpyrrolidinone were synthesized and tested for cytotoxicity against murine cancer cells B16 and L1210. One 1-benzo[f]chromanone derivative (4g), containing a 3,4,5-trimethoxy benzylidene moiety, was quite active also against human MDA-MB-435 melanoma cells. The structure and conformation of the target compounds were ascertained by single crystal X-ray analysis of four compounds.

Original languageEnglish (US)
Pages (from-to)341-348
Number of pages8
JournalArchiv der Pharmazie
Volume345
Issue number5
DOIs
StatePublished - May 1 2012

Keywords

  • Benzochromanone
  • Chalcones
  • Cytotoxicity
  • Tubulin
  • X-ray

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery

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