The Synthesis and Cytotoxicity of Novel Thiophene Derivatives Derived from 2-(4-Oxo-4,4-Dihydrothiazol-2-yl) Acetonitrile

Abstract

The reaction of the 2-(4-oxo-4,4-dihydrothiazol-2-yl)acetonitrile 1 with cyaclopentanone (2) afforded the condensed product 3. The latter underwent a series of heterocyclizations through its reaction with different reagents. Moreover, compound 1 underwent the Gewald's thiophene to afford compounds 15 and 17. The reaction of either hydrazine hydrate or phenylhydrazine with compound 17 gave the hydrazide derivatives 19a and 19b, respectively. The cytotoxicity of the newly synthesized products was measured towards the three cancer cell lines MCF-7, NCI-H460 and SF-268. The study showed that compounds 3, 5, 9c, 11, 13a, 13c, 17 and 19b were the most active compounds towards the three cancer cell lines.

Novel 1,2,4-oxadiazole compounds as PPAR-α ligand agonists: a new strategy for the design of antitumour compounds

“…These types of compounds have been widely used in the field of medicinal chemistry for drug design due to their broad spectrum of biphasic properties, including PPAR agonists. 26 However, recent reports on these types of compounds show that they can generate reactive metabolites leading to hepatotoxicity 27,28 because cytochrome P450 or myeloperoxidase (MPO) catalyses the S-oxidation of the thiophene ring to activate S-oxides and other intermediates that covalently bind to neutrophils and liver proteins. 29,30 It is for this reason that, although the natural compound showed promising PPAR-α agonistic activity, we decided to synthesise a series of compounds by making modifications to the thiophene ring (which can be found at position 5).…”

“…These types of compounds have been widely used in the field of medicinal chemistry for drug design due to their broad spectrum of biphasic properties, including PPAR agonists. 26…”

Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile

“…Thiazole moiety is present in many drugs such as thiamine (vitamin B 1 ), penicillin (antibiotic), sulfathiazole (antibacterial drug), 2-(4-chlorophenyl)thiazole-4-ylacetic (anti-inflammatory agent), thiabendazole [2-(4-thiazolyl)benzimidazole] (anthelmintic and fungicide), and niridazole [1-(5-nitro-2-thiazolyl)-2-imidazolidinone] (schistosomicidal agent) (23,24). Some thiazole derivatives have been recently proven to be anticancer agents (25). In the present study, we demonstrated the reaction of 4,5,6,7-tetrahydrobenzo[b]thiophene with thioglycolic acid to produce new thiazole derivatives incorporating thiophene moiety and studied their cytotoxicity against different cancer cell lines.…”

Synthesis, Characterization and Anticancer Activity of Some Benzothiazole and Thiazole Derivatives

“…Additionally, many compounds containing thiazole system have been investigated because of their broad spectrum of biological activities which include anticancer 17,18 , antimicrobial 19 , anti-inflammatory 20 , antioxidant 21 , antitubercular 22 and antiprotozoal activities 23 . The aforementioned biological activities together with the industrial importance of these compounds stimulated our interest for the synthesis of several new heterocyclic compounds containing benzothiazole moiety attached to or condensed with each of pyrrole, pyridine, quinoline, tetrazole, triazole, triazine, oxadiazole, thienopyrimidine, quinazoline, benzoxazole and pyrimidine moieties.…”