Egyptian Pharmaceutical Journal

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 17  |  Issue : 2  |  Page : 85--93

Synthesis of new indole derivatives using one- pot multicomponent reaction with antiproliferative towards normal and cancer cell lines


Nagwa M Fawzy1, Hanaa M Roaiah1, Enas M Awad1, Joanna Wietrzyk2, Magdalena Milczarek2, AbdelMohsen M Soliman3 
1 Department of Chemistry of Natural and Microbial Products, National Research Centre, Giza, Egypt
2 Department of Experimental Oncology, LudwikHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
3 Department of Therapeutic Chemistry, National Research Centre, Giza, Egypt

Correspondence Address:
Nagwa M Fawzy
Department of Chemistry of Natural and Microbial Products, National Research Centre, 33 ElBehousst, Dokki, Giza 12622
Egypt

Background and objectives Indoles derivatives are natural products, which are well known for their anticancer activity due to its ability to induce cell death for many cancer cell lines. The aim of this study is to synthesize some new heterocyclic compounds derived from 1H-indole-3-carbaldehyde, malononitrile, and different reagents namely: active methylene derivatives, amine derivatives, and resorcinol. The newly synthesized derivatives were prepared and confirmed by their IR, Mass, and 1NMR spectra; and were also tested for their antiproliferative potency towards human breast cancer (MCF-7) and normal murine fibroblast (BALB/3T3) cell lines. Materials and methods The synthesis of new indole derivatives (3a-e) was achieved by the three-component reactions of 1H-indole-3-carbaldehyde (1), ethyl 3-oxobutanoate, 5,5-dimethyl cyclohexane-1,3-dione (Dimidone), barbituric, thiobarbituric acid, and cyclohexanone (2a-e), respectively; and malononitrile in the presence of triethylamine. Compound (4) was afforded by fusing of compound (3a) with thiourea. Also, compounds (5a, b) were yielded by the grinding of compounds (3c, d) with formic acid. On the other side, one-pot synthesis of 7a-d has been achieved via three-component of 1H-indole-3-carbaldehyde (1), and malononitrile in the presence of amine derivatives (namely, 2,4-dinitroaniline, 3-nitroaniline, 3-bromoaniline, and 4-methoxyaniline) (6a-d), respectively, by condensation. Also, compounds (8, 9) were obtained by refluxing of compounds (7a, b) with formic acid. Compound (10) was afforded by condensing the mixture of 1H-indole-3-carbaldehyde (1) with resorcinol in the presence of malononitrile and triethylamine. The newly synthesized derivatives were tested for their antiproliferative potency towards human breast cancer (MCF-7) and normal murine fibroblast (BALB/3T3) cell lines. Results indicated that they showed significant in-vitro antiproliferative activity. Results and conclusion A novel protocol for the preparation of indole derivatives (3a-e) using the three-component reactions of 1H-indole-3-carbaldehyde (1) with active methylene compounds namely: ethyl 3-oxobutanoate, 5, 5-dimethy cyclohexane-1, 3-dione (Dimidone), barbituric acid, thiobarbituric acid, and cyclohexanone (2a-e); and malononitrile in ethanol and triethylamine as catalyst were proceeded in one step. Also, compounds (3a, 3c, d) were reacted with thiourea/and formic acid, respectively, to give compounds (4 and 5a, b). The 3-indole derivatives (7a-d) were formed via condensation of the amine derivatives (6a-d) with indole aldehydes (1) and malononitrile. Compounds (8 and 9) were afforded by condensation of compounds (7b, c) with formic acid, 2-amino-chromene (10) was produced by reaction of resorcinol, 1H-indole-3-carbaldehyde (1), and malononitrile. The in-vitro study showed that most of the prepared compounds gave similar activity towards breast cancer cell line MCF-7 but did not reveal the cytotoxic potency against normal cell line. This means that most of these compounds kill cancer cells but have no or slight effects on normal cells. The newly synthesized derivatives were tested for their antiproliferative potency towards human breast cancer (MCF-7) and normal murine fibroblast (BALB/3T3) cell lines. The results showed that the in-vitro antiproliferative activity of the prepared compounds was significant and could thus be investigated for further in vivo and pharmacokinetic studies.


How to cite this article:
Fawzy NM, Roaiah HM, Awad EM, Wietrzyk J, Milczarek M, Soliman AM. Synthesis of new indole derivatives using one- pot multicomponent reaction with antiproliferative towards normal and cancer cell lines.Egypt Pharmaceut J 2018;17:85-93


How to cite this URL:
Fawzy NM, Roaiah HM, Awad EM, Wietrzyk J, Milczarek M, Soliman AM. Synthesis of new indole derivatives using one- pot multicomponent reaction with antiproliferative towards normal and cancer cell lines. Egypt Pharmaceut J [serial online] 2018 [cited 2018 Dec 17 ];17:85-93
Available from: http://www.epj.eg.net/article.asp?issn=1687-4315;year=2018;volume=17;issue=2;spage=85;epage=93;aulast=Fawzy;type=0