Next Article in Journal
Intravenous Paracetamol in Adjunct to Intravenous Ketoprofen for Postoperative Pain in Children Undergoing General Surgery: A Double-Blinded Randomized Study
Previous Article in Journal
Impact of Different Types of Diet on Gut Microbiota Profiles and Cancer Prevention and Treatment
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

5-Arylidene(chromenyl-methylene)-thiazolidinediones: Potential New Agents against Mutant Oncoproteins K-Ras, N-Ras and B-Raf in Colorectal Cancer and Melanoma

1
Department of Pharmaceutical chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania
2
National Research and Development Institute for Cryogenics and Isotopic Technologies, ICSI Analytics, 4th Uzinei Street, RO-240050 Râmnicu Vâlcea, Romania
3
SC Biotech Corp SRL, 4th Uzinei Street, RO-240050 Râmnicu Vâlcea, Romania
*
Authors to whom correspondence should be addressed.
Medicina 2019, 55(4), 85; https://doi.org/10.3390/medicina55040085
Received: 18 December 2018 / Revised: 5 February 2019 / Accepted: 28 March 2019 / Published: 31 March 2019
  |  
PDF [3440 KB, uploaded 31 March 2019]
  |  

Abstract

Background and objectives: Cancer represents the miscommunication between and within the body cells. The mutations of the oncogenes encoding the MAPK pathways play an important role in the development of tumoral diseases. The mutations of KRAS and BRAF oncogenes are involved in colorectal cancer and melanoma, while the NRAS mutations are associated with melanoma. Thiazolidine-2,4-dione is a versatile scaffold in medicinal chemistry and a useful tool in the development of new antitumoral compounds. The aim of our study was to predict the pharmacokinetic/pharmacodynamic properties, the drug-likeness and lead-likeness of two series of synthetic 5-arylidene(chromenyl-methylene)-thiazolidinediones, the molecular docking on the oncoproteins K-Ras, N-Ras and B-Raf, and to investigate the cytotoxicity of the compounds, in order to select the best structural profile for potential anticancer agents. Materials and Methods: In our paper we studied the cytotoxicity of two series of thiazolidine-2,4-dione derivatives, their ADME-Tox properties and the molecular docking on a mutant protein of K-Ras, two isoforms of N-Ras and an isoform of B-Raf with 16 mutations. Results: The heterocyclic compounds strongly interact with K-Ras and N-Ras right after their posttranslational processing and/or compete with GDP for the nucleotide-binding site of the two GTPases. They are less active against the GDP-bound states of the two targets. All derivatives have a similar binding pattern in the active site of B-Raf. Conclusions: The data obtained encourage the further investigation of the 5-arylidene(chromenyl-methylene)-thiazolidinediones as potential new agents against the oncoproteins K-Ras, N-Ras and B-Raf. View Full-Text
Keywords: thiazolidine-2,4-dione; K-Ras; N-Ras; B-Raf; cytotoxicity; ADME-Tox; molecular docking thiazolidine-2,4-dione; K-Ras; N-Ras; B-Raf; cytotoxicity; ADME-Tox; 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).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Nastasă, C.; Tamaian, R.; Oniga, O.; Tiperciuc, B. 5-Arylidene(chromenyl-methylene)-thiazolidinediones: Potential New Agents against Mutant Oncoproteins K-Ras, N-Ras and B-Raf in Colorectal Cancer and Melanoma. Medicina 2019, 55, 85.

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.

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Medicina EISSN 1010-660X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top