Synthesis of 4,4\u2032-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities

José Eduardo Cadena-Cruz,Juan Carlos Romero-Benavides,Natalia Bailon-Moscoso,Jorge Heredia-Moya,Nadia V. Ortiz-Guamán,Kevin E. Murillo-Sotomayor,Luis M. Guamán-Ortiz

doi:10.1186/s13065-021-00765-y

José Eduardo Cadena-Cruz, Juan Carlos Romero-Benavides + Show 5 more

Open Access

https://doi.org/10.1186/s13065-021-00765-y

Copy DOI

Abstract

BackgroundPyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer.Results4,4ʹ-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4ʹ-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard.ConclusionSeveral derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 ± 0.6 µM and exhibited an IC50 of 9.9 ± 1.1 μM against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.

Highlights

Heterocycles are common structural units in marketed drugs and in targets in the drug discovery process
Chemistry The 4,4’-(arylmethylene)bis(1H-pyrazol-5-ols) 3 were synthesized using Sodium acetate (NaOAc) as catalyst following the scheme depicted in Scheme 1, using 70% EtOH as solvent at room temperature
In this work, 4,4ʹ-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) 3a–q were synthesized at room temperature using NaOAc as a catalyst in high to excellent yields and pure products were isolated by simple filtration

Summary

Conclusion

4,4ʹ-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) 3a–q were synthesized at room temperature using NaOAc as a catalyst in high to excellent yields and pure products were isolated by simple filtration. 4,4’‐[(4‐Nitrophenyl)methylene]bis(3‐methyl‐1‐phe‐ nyl‐1H‐pyrazol‐5‐ol) 3l Yield 97% as a yellow solid; mp 218.0–219.0 °C [Lit. 219–220 [47]]; 1H-NMR (500 MHz, DMSO-d6) δ: 8.17 (d, J = 8.9 Hz, 2 H, Ar–H), 7.69 (dd, J = 1.0, 8.6 Hz, 4 H, Ar–H), 7.51 (d, J = 8.9 Hz, 2 H, Ar–H), 7.45 (t, J = 8.0 Hz, 4 H, Ar–H), 7.26 (t, J = 7.4 Hz, 2 H, Ar–H), 5.13 (s, 1 H, CH), 2.34 (s, 6 H, CH3). 4,4’‐[(4‐Fluorophenyl)methylene]bis(3‐methyl‐1‐phe‐ nyl‐1H‐pyrazol‐5‐ol) 3m Yield 87% as a white solid; mp 183.8–185.8 °C [Lit. 181–183 [48]]; 1H-NMR (500 MHz, DMSO-d6) δ: 7.59—7.65 (m, 4H, Ar–H), 7.42 (dd, J = 8.3, 7.4 Hz, 4H, Ar–H), 7.24 (t, J = 7.2 Hz, 4H, Ar–H), 7.06 (t, J = 8.9 Hz, 2H, Ar–H), 4.91 (s, 1H, CH), 2.27 (s, 6H, CH3).

Introduction

Results and discussion