Synthesis, Antiproliferative Activity and Molecular Docking Studies of 1,3,5-Triaryl Pyrazole Compound as Estrogen α Receptor Inhibitor Targeting MCF-7 Cells Line

Abstract

This research has been successfully synthesized three compounds of 1,3,5-triaryl pyrazole derivatives by two steps reaction. Firstly, pyrazoline (4a-c) compound was obtained by one-pot reaction of aromatic ketones, aldehyde and hydrazine in basic condition. Then, pyrazole (5a-c) compound was obtained by oxidative aromatization of compound 4 in the presense of acetic acid. Chemical structure of predicted molecules was confirmed by FTIR, NMR and HRMS spectroscopy data analysis. Antiproliferative activity of compound 5a-c were evaluated by in vitro assay against MCF-7 cells line and molecular docking simulation against ERα (PDB ID: 3ERT) using MOE 2019. Biological evaluation result showed that pyrazole compounds had weak antiproliferative activity against MCF-7 cells with IC50 were > 1000 µM, whereas the docking studies agrees the result.

Microwave‐Assisted Synthesis, Antimicrobial Activities and Molecular Docking of Methoxycarboxylated Chalcone Derived Pyrazoline and Pyrazole Derivatives

“…The FTIR spectra of 4 a – g showed characteristic bands at 1601–1610 cm −1 which attributed to the υ C‐H band of the aromatic groups in the pyrazole network [22] . 1 HNMR spectra displayed a singlet at 7.09–7.29 ppm which corresponded to pyrazole configuration [39] . 13 CNMR spectra displayed sharp signals at 105.5–109.7 ppm attributed to pyrazole confirmation [35] .…”

Synthesis and Molecular Docking Study of 4-(3-(2-Chlorophenyl)-5-(2-Methoxyphenyl)-4,5-Dihydro-1H-Pyrazol-1-yl) Benzenesulfonamide as Antibreast Cancer Agent

“…The reaction mechanism of one-pot pyrazoline synthesis is initiated by the formation of chalcone compound as intermediate via Claisen-Schmidt reaction. Subsequently, the cyclization reaction occurs between chalcone with hydrazine to form pyrazoline compounds (Herfindo et al, 2020).…”

“…In previous work, we have synthesized 1,3,5-triaryl pyrazole with anti-proliferative activity against MCF-7 cell line (Herfindo et al, 2020). However, that work showed that the compounds are not active as anti-proliferative.…”

Novel Pyrazole‐Chalcone Hybrids: Synthesis and Computational Insights Against Breast Cancer

“…[14] Pyrazole represents one of the essential nitrogen-containing heterocycle, featured predominantly in numerous FDA-approved drugs (Figure 1) such as Avapritinib, Asciminib, Crizotinib, Darolutamide, Encorafenib, Erdafitinib, Pralsetinib, Pirtobrutinib, Pyrazofurin, and Ruxolitinib. [15] Pyrazole derivatives have become key pharmacophores in targeting various signaling molecules and transcriptional factors within the cancer pathway, [16] such as ER-α, [17,18] aromatase, Epidermal Growth Factor Receptor (EGFR), [19,20] and HER-2. [21] Studies by S. R. Stauffer et al have extensively explored pyrazole core substitutions to identify an optimized core, propyl-pyrazole triol (PPT), for high-affinity ER binding.…”

“…(Scheme 1) General synthesis of compound 8 a-n. Chemicals and conditions: (i) ethanol, acetic acid, warm, 1-4 h (ii) POCl 3 & DMF at 0 °C, 2-5 h, and neutralized through K 2 CO 3 ; (iii) K 2 CO 3 , Acetone, 0 °C -r.t., 4-5 h; (iv) aq.40 % NaOH & ethanol, r.t.,[12][13][14][15][16][17][18][19][20][21][22][23][24]…”