Next Article in Journal
Assessment of Antidepressant Effect of the Aerial Parts of Micromeria myrtifolia Boiss. & Hohen on Mice
Previous Article in Journal
Efficacy of Two Monoterpenoids, Carvacrol and Thymol, and Their Combinations against Eggs and Larvae of the West Nile Vector Culex pipiens
Previous Article in Special Issue
4,5-Diaryl 3(2H)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth
Article Menu
Issue 10 (May-2) cover image

Export Article

Open AccessArticle

Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones

Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland
Department of Biomolecular Chemistry, Medical University of Łódź, Mazowiecka 6/8, 92-215 Łódź, Poland
Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland
Author to whom correspondence should be addressed.
Academic Editors: Carla Boga and Gabriele Micheletti
Molecules 2019, 24(10), 1868;
Received: 26 April 2019 / Revised: 9 May 2019 / Accepted: 11 May 2019 / Published: 15 May 2019
(This article belongs to the Special Issue Design and Synthesis of Organic Molecules as Antineoplastic Agents)
PDF [2928 KB, uploaded 15 May 2019]


In the search for new anticancer agents, a library of variously substituted 3-methylidenechroman-4-ones was synthesized using Horner–Wadsworth–Emmons methodology. Acylation of diethyl methylphosphonate with selected ethyl salicylates furnished 3-diethoxyphosphorylchromen-4-ones which were next used as Michael acceptors in the reaction with various Grignard reagents. The adducts were obtained as the mixtures of trans and cis diastereoisomers along with a small amount of enol forms. Their relative configuration and preferred conformation were established by NMR analysis. The adducts turned up to be effective Horner–Wadsworth–Emmons reagents giving 2-substituted 3-methylidenechroman-4-ones, which were then tested for their possible cytotoxic activity against two leukemia cell lines, HL-60 and NALM-6, and against MCF-7 breast cancer cell line. All new compounds (14ao) were highly cytotoxic for the leukemic cells and showed a moderate or weak effect on MCF-7 cells. Analog 14d exhibited the highest growth inhibitory activity and was more potent than carboplatin against HL-60 (IC50 = 1.46 ± 0.16 µM) and NALM-6 (IC50 = 0.50 ± 0.05 µM) cells. Further tests showed that 14d induced apoptosis in NALM-6 cells, which was mediated mostly through the extrinsic pathway. View Full-Text
Keywords: 3-methylidenechroman-4-ones; Michael addition; Horner–Wadsworth–Emmons olefination; cancer cell lines; apoptosis 3-methylidenechroman-4-ones; Michael addition; Horner–Wadsworth–Emmons olefination; cancer cell lines; apoptosis

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Kędzia, J.; Bartosik, T.; Drogosz, J.; Janecka, A.; Krajewska, U.; Janecki, T. Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones. Molecules 2019, 24, 1868.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top