Synthesis, Docking, and Anticancer Activity of New Thiazole Clubbed Thiophene, Pyridine, or Chromene Scaffolds

Abstract

2‐Cyanoacetamido‐4‐methylthiazole (1) was utilized as a versatile precursor for the construction of new thiazole clubbed thiazolidine, thiophene, pyridine, or chromene scaffold. The base‐catalyzed addition of 1 to phenyl isothiocyanate followed by subsequent treatment of the produced thiocarbamoyl intermediate with ethyl chloroacetate or chloroacetonitrile furnished the corresponding thiazolyl‐thiazolidine and thiazolyl‐thiophene hybrids. The reactions of compound 1 with chemical reagents, namely, acetylacetone, malononitrile, and/or 2‐(4‐anisylidene)‐malononitrile have been studied and furnished the corresponding thiazole‐pyridine hydrides 8–10. Furthermore, treatment of the precursor 1 with salicylaldehyde, various aryl diazonium chlorides, and/or aromatic aldehydes afforded their corresponding thiazolyl‐chromene hybrid 12, arylhydrazono‐nitriles 13, and unsaturated nitriles 14, respectively. The cytotoxicity of the synthesized compounds was screened against the cell lines HepG2, HCT‐116, and MCF‐7. Compounds 8, 10, and 12 recorded the best results, which was illustrated by molecular docking. Molecular Operating Environment molecular docking calculations carried out here is to rationalize correlation between docking results and biological data of thymidylate synthase (Protein Data Bank code: IHVY) inhibition. Docking has been carried out in the same co‐crystallographic inhibitor binding site to predict if the binding mode of active compounds is analogous to that of native inhibitor.

Synthesis and synthetic applications of cyanoacetamides

“…Heating of compound 38 with 29a,b or 24a in DMF/EtOH at reflux in the presence of triethylamine, resulted in the formation of 5-acetyl(or-benzoyl)-4-amino-2-phenylaminothiophene-3carboxamides 39a-c (Scheme 16). 80,81…”

Anticancer and molecular docking studies of some new pyrazole-1-carbothioamide nucleosides

“…MOE builder tool was used in building the ligand structures. Next, the correct atom types (including hybridization states) and correction of the bond types were defined, hydrogen atoms were added, charges were assigned to each atom, and then the structures were subject to energy minimization using AMBER10:EHT method until a gradient of 0.01 was reached, this process was applied for co-crystallographic or the ligand structures [31,32].…”

Synthesis, Molecular Docking Study, and Cytotoxic Activity against MCF Cells of New Thiazole–Thiophene Scaffolds

“…Over the last several years, hybrid drug design has been used as a prime method for developing novel anticancer therapies that can solve many of the pharmacokinetic disadvantages of traditional anticancer drugs. Thus, several studies have indicated that thiazole–thiophene hybrids have important anticancer activity [ 24 ].…”