1,2,3-Triazolyl pyrazole derivatives as anti-cancer agents: biological evaluation and molecular docking

Manjunatha Bhat; Nagaraja G. K.; Reshma Kayarmar; Sreedhara Ranganath Pai K; Subhankar Biswas; Mohammed Shafeeullah R.

Abstract

1,2,3-Triazolyl pyrazole derivatives as anti-cancer agents: biological evaluation and molecular docking

Author(s): Manjunatha Bhat, Nagaraja G. K., Reshma Kayarmar, Sreedhara Ranganath Pai K, Subhankar Biswas and Mohammed Shafeeullah R.

A series of newcompounds3-{5-methyl-1-[2-methyl-3-(trifluoromethyl) phenyl/substituted phenyl]-1H-1,2,3-triazol- 4-yl}-1-(aryl)-1H-pyrazole-4-carbaldehydes(5a-n)wassynthesized by a Vilsmeier-Haackformylation reaction of 4- {(1E)-1-[2-(aryl) hydrazinylidene]ethyl}-5-methyl-1-[2-methyl-3-(trifluoromethyl)phenyl/substituted phenyl]-1H- 1,2,3-triazole (4a-n) with Phosphorous oxychloride-DMF mixture. The newly synthesized compounds were elucidated by their spectral studies. Further, the in-vitro anti-cancer activities of the newly synthesized compounds(5a-n)were carried out against breast cancer cell lines MCF-7 and MDA-MB-231. The compounds 5c, 5f, 5g, 5j, 5m and 5n exhibits significant activities against both the cell lines MCF-7 and MDA-MB-231 with IC50 values in the range of 6.8-9.8 μM and 11.1-14.1 μM respectively. The anti-cancer results were further supported by the in-silico molecular docking studies for the inhibition of Epidermal growth factor receptor (EGFR) kinase (PDB ID: 2A91) and human estrogen receptor (PDB ID: 2IOK) respectively, showed minimum binding energies and good affinities towards the active pockets comparable with the standard drug Toremifene. Thus, they may be considered as good inhibitors of EGFR kinase domain (PDB ID: 2A91) and human estrogen receptor (PDB ID: 2IOK).

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