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

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 i...

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Bibliographic Details
Published in:Journal of heterocyclic chemistry 2019-03, Vol.56 (3), p.1063-1074
Main Authors: Radwan, Ahmed S., Khalid, Mohamed A. A.
Format: Article
Language:English
Subjects:
Acetylacetone
Aldehydes
Anticancer properties
Aromatic compounds
Binding sites
Biological effects
Chemical reactions
Crystallography
Cyanide
Cytotoxicity
Data banks
Hybrids
Inhibitors
Malononitrile
Molecular docking
Nitriles
Organic chemistry
Precursors
Proteins
Reagents
Scaffolds
Toxicity
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Summary: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.
ISSN:0022-152X
1943-5193
DOI:10.1002/jhet.3493