Investigation on the synthesis of new 3-[4-(arylalkoxy)phenylethyl]-2-thioxo-1,3-thiazolidin-4-ones and their biological evaluation against cancer cells

Abstract

International audienceHerein, we report on the 5-step synthesis of new 3-[4-(arylalkoxy)phenylethyl]-2-thioxo-1,3-thiazolidin-4-ones without 5-arylidene fragments starting from tyramine The construction involved protection with Boc(2)O, regioselective O-alkylation, deprotection with 6 M HCl, neutralization, and finally reaction of bis(carboxymethyl) trithiocarbonate under microwave irradiation. The intermediates and the N-substituted rhodanine have been also evaluated for their in vitro inhibition of cell proliferation (Huh7, Caco 2, MDA-MB231, HCT 116, PC3, NCI-H727, HaCat). Two compounds have shown a selective potent activity against HCT116 cell line

Anticancer Profile of Rhodanines: Structure–Activity Relationship (SAR) and Molecular Targets—A Review

“…The antiproliferative activity of the N-3-substituted rhodanines was also confirmed by Déliko Dago et al [28], who evaluated the biological activity of some 3-[4-(arylalkoxy)phenyl ethyl]-2-thioxo-1,3-thiazolidin-4-one (compound 4) and 3-[2-(4-hydroxyphenyl)ethyl]-2thioxo-1,3-thiazolidin-4-one (compound 5) against representative tumor cell lines (Figure 3). The results of the survival assays showed that 2-thioxo-1,3-thiazolidin-4-one derivative 4 exhibited selective antitumor activity in the colorectal adenocarcinoma HCT 116 cell line, with an IC 50 value of 10 µM, and did not inhibit the growth of normal fibroblasts (IC 50 > 25 µM).…”

“…Figure13. The structures of thiazolyl-rhodanine derivative(27) and its thiazolidine-2,4-dione analogue(28).…”

Facile synthesis of 5-arylidene rhodanine derivatives using Na2SO3 as an eco-friendly catalyst. Access to 2-mercapto-3-aryl-acrylic acids and a benzoxaborole derivative

“…Heterocycles display an impressively high biological potential and were also used as important intermediates in the area of organic synthesis. Derivatives containing the 2-thioxothiazolidin-4-one (rhodanine) substructure are an interesting and important part of this wide library of bioactive compounds and exhibit a wide variety of biological activities, 1,2 as anti-fungal, 3 antibacterial, [4][5][6][7] anti-inflammatory, [8][9][10] anti-cancer, [11][12][13] anti-Alzheimer, 14,15 anti-viral [16][17][18] and anti-diabetic (Figure 1). [19][20][21][22] More precisely, they act, for example, as inhibitors of aldose reductase, protein tyrosine phosphatase PTP, aggregation of Tau proteins, HIV-1 integrase, hepatitis C virus, protease and - In addition, they are versatile synthetic intermediates since they can undergo many chemical transformations, such as hydrolysis in basic medium to lead to mercaptoacrylic acids, 23 Michael-type addition, 24 Diels Alder reactions to access dihydropyrans 25 and 2-thioxopyrano [2,3-d] [1,3]thiazoles.…”

Synthesis and Antiproliferative Evaluation of 5′‐Arylchalcogenyl‐3‐(phenylselanyl‐triazoyl)‐thymidine

“…Furthermore, the antitumoral behavior for organochalcogenium compounds is also described. In this context, molecules containing sulfur, selenium, and tellurium are related by presenting neovascular activity in tumor cells of colon, lung, breast, hepatoma, neuroepithelioma, melanomas, glioblastoma, fibrosarcoma, prostate, leukemia, and brain antitumor activity . In the search for antitumoral activity for nucleosides combined with the biological properties of molecules containing chalcogenium, our research group recently published studies on the effectivity of zidovudine derivatives containing chalcogenium .…”