Synthesis, antimicrobial and anti-cancer activities of some new N-ethyl, N-benzyl and N-benzoyl-3-indolyl heterocycles

Abstract

Synthesis, antimicrobial and anti-cancer activities of some newN-ethyl,N-benzyl andN-benzoyl-3-indolyl heterocyclesA series of 1-(N-substituted-1H-indol-3-yl)-3-arylprop-2-ene-1-ones (2a, b-4a, b) were prepared and allowed to react with urea, thiourea or guanidine to give pyrimidine derivatives5a, b-13a, b. Reaction of2a, b-4a, bwith ethyl acetoacetate in the presence of a base gave cyclohexanone derivatives14a, b-16a, b. Reaction of the latter compounds with hydrazine hydrate afforded indazole derivatives17a, b-19a, b. On the other hand, reaction of2a, b-4a, bwith some hydrazine derivatives, namely hydrazine hydrate, acetyl hydrazine, phenylhydrazine and benzylhydrazine hydrochloride, led to the formation of pyrazole derivatives20a, b-31a, b. Moreover, reaction of2a, b-4a, bwith hydroxylamine hydrochloride gave isoxazole derivatives32a, b-34a, b. The newly synthesized compounds were tested for their antimicrobial activity and showed that 4-(N-ethyl-1H-indol-3-yl)-6-(p-chlorophenyl)-pyrimidine-2-amine (11b) was the most active of all the test compounds towardsCandida albicanscompared to the reference drug cycloheximide. Eighteen new compounds, namely pyrimidin-2(1H)-ones5a, b-7a, b, pyrimidin-2(1H)-thiones8a, b-10a, band pyrimidin-2-amines11a, b-13a, bderivatives, were tested for theirin vitroantiproliferative activity against HEPG2, MCF7 and HCT-116 cancer cell lines. 4-(N-ethyl-1H-indol-3-yl)-6-(p-methoxyphenyl)-pyrimidin-2-amine (11a)was found to be highly active withIC50of 0.7 μmol L-1.