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Synthesis, Docking, and Anticancer Activity of New Thiazole Clubbed Thiophene, Pyridine, or Chromene Scaffolds
Author(s) -
Radwan Ahmed S.,
Khalid Mohamed A. A.
Publication year - 2019
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.3493
Subject(s) - chemistry , malononitrile , thiazole , thiophene , pyridine , docking (animal) , salicylaldehyde , combinatorial chemistry , reagent , active site , stereochemistry , medicinal chemistry , organic chemistry , enzyme , catalysis , schiff base , medicine , nursing
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.