Synthesis and anticancer activity of some thiophene, thienyl-thiazole, and thienyl-benzofuran analogues

N-(Anisyl)-5-(2-chloroacetamido)-4-cyano-3-methylthiophene-2-carboxamide (3) was synthesized and reacted with several nucleophilic reagents. The reactions with sulfur nucleophiles (namely, mercaptoacetic acid, ethyl 2-mercaptoacetate, 5-(phenylamino)-1,3,4-thiadiazole-2-thiol, 2-mercapto-4,6-dimethyl-nicotinonitrile, 4-anilino-3-arylazo-4-mercapto-butenones, ethyl 3-anilino-2-arylazo-3-mercapto-acrylates, and ammonium thiocyanate) yielded the corresponding sulfide, thiophene, or thiazolin-4-one derivatives, respectively. The reaction with salicylaldehyde (an example of oxygen nucleophile) furnished the targeting benzofuran compound 21. The reactions with nitrogen nucleophiles (namely, piperidine and aniline) yielded the corresponding thiophene-carboxamide derivatives 23 and 25, respectively. IR, H-1 NMR, and C-13 NMR were used to deduce the structures of the target thiophene containing compounds. The effect of the synthesized thiophenes on the viability of HepG2, A2780, and A2780CP was determined. The most effective drug was shown by the thienopyridine-carboxamide compound 11, against liver cancer cell lines (HepG2) and ovarian cancer cell lines (A2780CP and A2780), whose IC50 values were remarkably near those of Sorafenib, the antitumor drug.

Automated summary

N-(Anisyl)-5-(2-chloroacetamido)-4-cyano-3-methylthiophene-2-carboxamide (3) was reacted with various nucleophilic reagents, such as sulfur, oxygen, and nitrogen nucleophiles, to obtain corresponding derivatives. The synthesized thiophene compounds were characterized by IR, H-1 NMR, and C-13 NMR. Among them, the thienopyridine-carboxamide compound 11 showed the most potent antitumor activity against liver cancer and ovarian cancer cell lines, with IC50 values similar to Sorafenib.