One-pot synthesis of cinnamylideneacetophenones and their in vitro cytotoxicity in breast cancer cells

David J Weldon; Marilyn D Saulsbury; Joshua Goh; Leah Rowland; Petreena Campbell; Laijia Robinson; Calvin Miller; Joshua Christian; Louisa Amis; Nia Taylor; Cassandra Dill; Willie Davis Jr; Stanley L Evans; Eileen Brantley

doi:10.1016/j.bmcl.2014.05.089

One-pot synthesis of cinnamylideneacetophenones and their in vitro cytotoxicity in breast cancer cells

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3381-4. doi: 10.1016/j.bmcl.2014.05.089. Epub 2014 Jun 4.

Authors

Affiliations

¹ Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Loma Linda University, Loma Linda, CA, United States.
² Department of Pharmaceutical Sciences, Hampton University, Hampton, VA, United States.
³ Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, United States.
⁴ Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, United States; Department of Chemistry, Geology and Physics, School of Mathematics, Science & Technology, Elizabeth City State University, Elizabeth City, NC, United States.
⁵ Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Loma Linda University, Loma Linda, CA, United States; Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, United States.
⁶ Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, United States.
⁷ Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Loma Linda University, Loma Linda, CA, United States; Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, United States; Department of Chemistry, University of California, Riverside, CA 92521, United States. Electronic address: ebrantley@llu.edu.

Abstract

A series of cinnamylideneacetophenones were synthesized via a modified Claisen-Schmidt condensation reaction and evaluated for cytotoxicity against breast cancer cells using the Alamar Blue™ assay. Derivatives 17 and 18 bearing a 2-nitro group on the B ring, exhibited sub-micromolar cytotoxicity in MCF-7 cells (IC50=71 and 1.9 nM), respectively. Derivative 17 also displayed sub-micromolar (IC50=780 nM) cytotoxicity in MDA-MB-468 cells. Additionally, 17 and 18 displayed significantly less cytotoxicity than the chemotherapeutic doxorubicin in non-tumorigenic MCF-10A cells. This study provides evidence supporting the continued development of nitro-substituted cinnamylideneacetophenones as small molecules to treat breast cancer.

Keywords: Breast cancer; Chalcone derivatives; Cytotoxicity; Estrogen receptor; Leinamycin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Ketones / chemical synthesis
Ketones / chemistry
Ketones / pharmacology*
MCF-7 Cells
Molecular Structure
Nitrobenzenes / chemical synthesis
Nitrobenzenes / chemistry
Nitrobenzenes / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Ketones
Nitrobenzenes

Abstract

Publication types

MeSH terms

Substances

Grants and funding