Synthesis and In Vitro Cytotoxicity of New 3-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazoles
DOI:
https://doi.org/10.12970/2308-8044.2015.03.01.2Keywords:
1,2,3-triazoles, Vilsmeier-Haack reaction, Knoevenagel condensation, anticancer, MCF-7, HepG2, A549, HFB4.Abstract
In this paper we present the synthesis of a novel series of 3-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazoles 3-6 by employing Vilsmeier-Haack reaction followed by Knoevenagel condensation on 1-aryl-3-acetyl-4-methyl-1,2,3-triazoles 1a,b. The cytotoxicity and in vitro anticancer evaluation of the prepared compounds have been assessed against four different human cancer cell lines including breast MCF-7; liver HepG2 and lung cancer A549 as well as human normal melanocyte HFB4. The results revealed that the prepared compounds exert their actions in MCF-7 and HepG2. Compounds 4a and 6a revealed promising anticancer activity compared to the activity of the commonly used anticancer drug, doxorubicin. MCF-7 cells are slightly more sensitive to the tested compounds than HepG2 cells.
References
Boohaker RJ, Lee MW, Vishnubhotla P, Perez JM, Khaled AR. The use of therapeutic peptides to target and to kill cancer cells. Cur Med Chem 2011; 19: 3794-804. http://dx.doi.org/10.2174/092986712801661004
Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature 2009; 458: 719-24. http://dx.doi.org/10.1038/nature07943
Beaglehole R, Bonita R, Magnusson R. Global cancer prevention: an important pathway to global health and development. Public Health 2011; 125: 821-31. http://dx.doi.org/10.1016/j.puhe.2011.09.029
Monje M, Dietrich J. Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis. Beh Brain Res 2012; 227: 376-9. http://dx.doi.org/10.1016/j.bbr.2011.05.012
Monsuez JJ, Charniot JC, Vignat N, Artigou JY. Cardiac side-effects of cancer chemotherapy. Int J Card 2010; 144: 3-15. http://dx.doi.org/10.1016/j.ijcard.2010.03.003
(a) El-Gamal MI, Sim TB, Hong JH, Cho JH, Yoo KH, Oh CH. Synthesis of 1H-pyrazole-1-carboxamide derivatives and their antiproliferative activity against melanoma cell line. Arch Pharm 2011; 344: 197-204. http://dx.doi.org/10.1002/ardp.201000057
(b) El-Gamal MI, Oh CH. Design and synthesis of 3-(3-chloro-4-substituted phenyl)-4-(pyridin-4-yl)-1H-pyrazole-1-carboxamide derivatives and their antiproliferative activity against melanoma cell line. Bull Korean Chem Soc 2011; 32: 821-8. http://dx.doi.org/10.5012/bkcs.2011.32.3.821
(c) El-Gamal MI, Choi HS, Cho HG, Hong JH, Yoo KH, Oh CH. Design, synthesis, and antiproliferative activity of 3,4-diarylpyrazole-1-carboxamide derivatives against melanoma cell line. Arch Pharm 2011; 344: 745-54. http://dx.doi.org/10.1002/ardp.201000375
Choi WK, El-Gamal MI, Choi HS, Baek D, Oh CH. New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies. Eur J Med Chem 2011; 46: 5754-62. http://dx.doi.org/10.1016/j.ejmech.2011.08.013
(a) El-Gamal MI, Park YS, Chi DY, Yoo KH, Oh CH. New triarylpyrazoles as broad-spectrum anticancer agents: design, synthesis, and biological evaluation. Eur J Med Chem 2013, 65: 315-22. http://dx.doi.org/10.1016/j.ejmech.2013.04.067
(b) El-Gamal MI, Choi HS, Yoo KH, Baek D, Oh CH. Antiproliferative diarylpyrazole derivatives as dual inhibitors of the ERK pathway and COX-2. Chem Biol Drug Des 2013; 82: 336-47. http://dx.doi.org/10.1111/cbdd.12186
Mohamed HA, Abdel-Latif E, Abdel-Wahab BF, Awad GEA. Novel Antimicrobial Agents: Fluorinated 2-(3-(Benzofuran-2-yl)pyrazol-1-yl)thiazoles. Int J Med Chem 2013; 2013: 1-6. http://www.hindawi.com/journals/ijmc/2013/986536/
El-Zahany EAM, El-Seidy AMA, Drweesh SA, Youssef NS, Abdel-Wahab BF, El-Beih A. Synthesis, characterization and biological activity of some transition metal complexes of Pyrrolidine derivatives. J Appl Sci Res 2013; 9: 2268-78.
Abdel-Wahab BF, Sediek A, Mohamed HA, Awad GEA. Novel 2-pyrazolin-1-ylthiazoles as Potential Antimicrobial Agents. Lett Drug Des Discov 2013; 10: 111-8. http://dx.doi.org/10.2174/157018013804725143
Pokhodylo NT, Savka RD, Matiichuk VS, Obushak ND. Synthesis and selected transformations of 1-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)ethanones and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl]ethanones. Russ J Gen Chem 2009; 79: 309-14. http://dx.doi.org/10.1134/S1070363209020248
Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature 1993; 366: 362-5. http://dx.doi.org/10.1038/366362a0
Mackay S, Gilmore CJ, Edwards C, Stewart N, Shankland K. Maxus Computer Program for the Solution and Refinement of Crystal Structures. Bruker Nonius, The Netherlands, MacScience, Japan & The University of Glasgow 1999.
