title: Synthesis, antimicrobial and anti-cancer activities of some new N-ethyl, N-benzyl and N-benzoyl-3-indolyl heterocycles.
abstract: A 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 derivatives 5a, b-13a, b. Reaction of 2a, b-4a, b with ethyl acetoacetate in the presence of a base gave cyclohexanone derivatives 14a, b-16a, b. Reaction of the latter compounds with hydrazine hydrate afforded indazole derivatives 17a, b-19a, b. On the other hand, reaction of 2a, b-4a, b with some hydrazine derivatives, namely hydrazine hydrate, acetyl hydrazine, phenylhydrazine and benzylhydrazine hydrochloride, led to the formation of pyrazole derivatives 20a, b-31a, b. Moreover, reaction of 2a, b-4a, b with hydroxylamine hydrochloride gave isoxazole derivatives 32a, 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 towards Candida albicans compared to the reference drug cycloheximide. Eighteen new compounds, namely pyrimidin-2(1H)-ones 5a, b-7a, b, pyrimidin-2(1H)-thiones 8a, b-10a, b and pyrimidin-2-amines 11a, b-13a, b derivatives, were tested for their in vitro antiproliferative 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 with IC(50) of 0.7 μmol L⁻¹.
authors: Chemistry Department of Natural Compounds, National Research Centre, Cairo, Egypt. eslamelsawy@gmail.com
authors: Eslam Reda
authors: ER
authors: El-Sawy
authors: Adel Hamed
authors: AH
authors: Mandour
authors: Khaled
authors: K
authors: Mahmoud
authors: Inas Ezz-Eldin
authors: IE
authors: Islam
authors: Heba Mohamed
authors: HM
authors: Abo-Salem
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052978:Disk Diffusion Antimicrobial Tests; D015195:Drug Design; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D047188:Chalcones; D003512:Cyclohexanones; D007211:Indoles; D007555:Isoxazoles; D011720:Pyrazoles; D011743:Pyrimidines