Graph Theoretical analysis, in silico modeling and molecular dynamic studies of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substituted phenyl)-N,N-dimethylethen-1-amine derivatives for the treatment of breast cancer.

Autor:	Panneerselvam T; Department of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam-637205, Namakkal, Tamil Nadu, India., Kunjiappan S; Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy - 502 294, Telangana, India., Govindaraj S; Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy - 502 294, Telangana, India., Gopal M; Department of Pharmacognosy, Swamy Vivekananda College of Pharmacy, Elayampalayam-637205, Namakkal, Tamil Nadu, India., Natarajan K; Department of Pharmaceutical Chemistry, KMCH College of Pharmacy, Kalapatti Road, Kovai estate, Coimbatore- 641048, Tamilnadu, India., Hegde YM; Department of Pharmaceutics, Swamy Vivekananda College of Pharmacy Elayampalayam-637205, Namakkal, Tamil Nadu, India., Shanmugam N; Department of Pharmaceutics, Swamy Vivekananda College of Pharmacy Elayampalayam-637205, Namakkal, Tamil Nadu, India., Srinivas G; Department of Pharmaceutics, Swamy Vivekananda College of Pharmacy Elayampalayam-637205, Namakkal, Tamil Nadu, India., Ravi K; Department of Pharmaceutics, Swamy Vivekananda College of Pharmacy Elayampalayam-637205, Namakkal, Tamil Nadu, India., Natarajan V; Department of Pharmaceutics, Swamy Vivekananda College of Pharmacy Elayampalayam-637205, Namakkal, Tamil Nadu, India.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2022 Dec 05. Date of Electronic Publication: 2022 Dec 05.
DOI:	10.2174/1871520623666221205140328
Abstrakt:	Background: We synthesized a series of novel amide derivatives of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substituted phenyl)-N,N-dimethylethen-1-amine [5a-5r] and assessed for their antiproliferative activity against human breast cancer cell line MCF7 by using MTT assay. Graph Theoretical analysis, in silico modeling, molecular dynamic studies, and ADME profile were screened for the synthesized compounds. Based on the observed report, the significant compounds were chosen for their anticancer activity. Graph Theoretical analysis, in silico modeling and molecular dynamic studies of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substitutedphenyl)-N,N-dimethylethen-1-amine derivatives for the treatment of breast cancer. Methods: 5-((2-chloropyridin-4-yl)oxy) (2-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1- (4-substituted phenyl) -N,N-dimethylethen-1-amine [5a-5r] was synthesized using 2-bromo-1-phenylethanone and (5-(2-chloropyridin-4-yloxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylmethanamine with different aromatic aldehydes and their characterization studies were evaluated by IR, NMR, and mass spectral analysis. Results: The compound 2-(4-methylphenyl)-1-(5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5a and 2-(2-methylphenyl)-1-(5-((2-chloro pyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5c in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 3.3 mM for MCF-7 cells, and produced dramatic cell cycle arrest at EGFR phase as an indicator of apoptotic cell death induction. Conclusion: Based on their high potency in the cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess the potential to design more potent compounds for intervention with cancer cell proliferation. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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