Next Article in Journal
Evaluation of the Antimicrobial Activity and Cytotoxicity of Different Components of Natural Origin Present in Essential Oils
Previous Article in Journal
Hydrogen-Bonded Organic–Inorganic Hybrid Based on Hexachloroplatinate and Nitrogen Heterocyclic Cations: Their Synthesis, Characterization, Crystal Structures, and Antitumor Activities In Vitro
Article Menu

Export Article

Open AccessArticle
Molecules 2018, 23(6), 1398; https://doi.org/10.3390/molecules23061398

Design, Synthesis, Anticancer Evaluation and Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin

1
Department of Chemistry, Jazan University, Jazan 45142, Saudi Arabia
2
Department of Natural and Microbial Products, National Research Center, Dokki, Cairo 12622, Egypt
3
Genetics & Cell Biology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
*
Author to whom correspondence should be addressed.
Received: 12 May 2018 / Revised: 24 May 2018 / Accepted: 2 June 2018 / Published: 8 June 2018
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [3819 KB, uploaded 8 June 2018]   |  

Abstract

Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 was synthesized via the reaction of furochromone carbaldehyde (1) with Curcumin (2) using pipredine as catalyst. Also, novel, 4,9-dimethoxy-5H-furo [3, 2-g] chromen-5-one derivatives 4ad, 6ad, 7, 8ad, 9 and 10 were synthesized by the reactions of furochromone carbaldehyde (1) with different reagents (namely: appropriate amine 3ad, appropriate hydrazine 5ad, hydroxylamine hydrochloride, urea/thiourea, malononitrile, malononitrile with hydrazine hydrate). The structure of the synthesized products had been confirmed from their spectroscopic data (IR, 1H-NMR, 13C-NMR and mass spectra). In the present investigation, the newly synthesized products were screened using the MTT colorimetric assay for their in vitro inhibition capacity in two human cancer cell lines (hepatocellular carcinoma (HEPG2) and breast cancer (MCF-7) as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-flurouracil and doxorubicin. The anticancer activity results indicated that the synthesized products 4c and 8b showed growth inhibition activity against HEPG2 cell line and synthesized products 4b and 8a showed growth inhibition activity against MCF-7, but with varying intensities in comparison to the known anticancer drugs, 5-flurouracil and doxorubicin. Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Furthermore, Curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in cancer cells. Therefore, we used molecular modelling to study in silico the possible inhibitory effect of CDK2 by Curcumin derivatives as a possible mechanism of these compounds as anticancer agents. The molecular docking study revealed that compounds 4b, 8a and 8b were the most effective compounds in inhibiting CDk2, and, this result was in agreement with cytotoxicity assay. View Full-Text
Keywords: furochromone carbaldehyde; Curcumin; anticancer activity; cytotoxicity; human cancer cell lines; molecular docking furochromone carbaldehyde; Curcumin; anticancer activity; cytotoxicity; human cancer cell lines; molecular docking
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).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Borik, R.M.; Fawzy, N.M.; Abu-Bakr, S.M.; Aly, M.S. Design, Synthesis, Anticancer Evaluation and Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin. Molecules 2018, 23, 1398.

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