Next Article in Journal
A Review: The Bioactivities and Pharmacological Applications of Polygonatum sibiricum polysaccharides
Next Article in Special Issue
Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages
Previous Article in Journal
Determination of Ten Macrolide Drugs in Environmental Water Using Molecularly Imprinted Solid-Phase Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry
Previous Article in Special Issue
Antioxidant Structure–Activity Relationship Analysis of Five Dihydrochalcones
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(5), 1174; https://doi.org/10.3390/molecules23051174

Synthesis and Evaluation of Antiplasmodial Activity of 2,2,2-Trifluoroethoxychalcones and 2-Fluoroethoxy Chalcones against Plasmodium falciparum in Culture

1
Fluoroorganic Laboratory, Center for Fire, Explosive and Environment Safety, Delhi-110 054, India
2
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India
3
Department of Chemistry, Hansraj College, University of Delhi, Delhi 110 007, India
4
Department of Chemistry, Sri Venkateswara College, University of Delhi, New Delhi 110 021, India
5
Department of Chemistry, Shivaji College, University of Delhi, New Delhi 110 027, India
*
Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 2 April 2018 / Revised: 29 April 2018 / Accepted: 9 May 2018 / Published: 14 May 2018
(This article belongs to the Special Issue Chalcone: A Privileged Structure in Medicinal Chemistry)
Full-Text   |   PDF [28572 KB, uploaded 14 May 2018]   |  

Abstract

A new class of compounds comprising two series of chalcones with 2,2,2-trifluoroethoxy group and 2-fluoroethoxy groups were synthesized and screened for in vitro antiplasmodial activity against Plasmodium falciparum (3D7) using the [3H] hypoxanthine incorporation inhibition assay. Chalcones with 2,2,2-trifluoroethoxy groups substituted on the p- and m-positions of the 1-phenyl ring showed weak antiplasmodial activity, while compounds substituted on the o-position of the 1-phenyl ring displayed enhanced antiplasmodial activity, thus indicating that 2,2,2-trifluoroethoxy groups on the 1-phenyl ring of chalcones show position-dependent antiplasmodial activity. Of the 34 compounds synthesized, chalcones 3a and 3f exhibited significant inhibitory effects, with IC50 values of 3.0 μg/mL and 2.2 μg/mL, respectively. Moreover, these compounds 3a and 3f showed profound antiplasmodial activity in combination with artemisinin in vitro. The most active molecules, 3a, and 3f, were further assessed for their cytotoxicity towards mammalian Vero cells and the selectivity index (SI) values are 8.6, and 8.2 respectively, being considered non-toxic. We also studied the antiplasmodial activity of 2-fluoroethoxychalcones to discern the effect of the number of fluorine atoms in the fluoroethoxy group. Our results showed that chalcones with 2-fluoroethoxy group on the 1-phenyl ring exhibited more enhanced inhibitory effects on the growth of parasites than their trifluoro analogues, which reveals that monofluoroethoxy group is generally more effective than trifluoroethoxy group in the inhibition of parasite growth. Thus o-2,2,2-trifluoroethoxychalcones (Series 3) and 2-fluoroethoxychalcones may serve as good antiplasmodial candidates for future further development. View Full-Text
Keywords: fluoroethoxychalcones; antiplasmodial activity; Plasmodium falciparum (3D7); artemisinin combination therapy; cytotoxicity fluoroethoxychalcones; antiplasmodial activity; Plasmodium falciparum (3D7); artemisinin combination therapy; cytotoxicity
Figures

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

SciFeed

Share & Cite This Article

MDPI and ACS Style

Devi, K.; Rajendran, V.; Ayushee; Rangarajan, T.M.; Singh, R.P.; Ghosh, P.C.; Singh, M. Synthesis and Evaluation of Antiplasmodial Activity of 2,2,2-Trifluoroethoxychalcones and 2-Fluoroethoxy Chalcones against Plasmodium falciparum in Culture. Molecules 2018, 23, 1174.

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

1

Comments

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