Arylhydrazono/Aryldiazenyl Pyrazoles: Green One-Pot Solvent-Free Synthesis and Anticancer Evaluation

Abstract

Aims: The aim of this study was to synthesize and evaluate the biological activity of newer pyrazole derivatives. Background: Cancer is one of the world's top noncommunicable disease growing rapidly with an approximately 18.1 million new cases and 10 million deaths in the last year. Despite the availability of numerous classes of anticancer agents, treatment for all types of cancers is still a long way due to severe adverse drug reactions and drug resistance. Therefore, there is a pressing need to develop newer safer and effective anticancer agents. Objective: Our objective in this study was the greener one-pot synthesis of newer pyrazole derivatives with solvent-free method as an alternative strategy for synthesizing new agents with potential anticancer activity. Method: Herein, we describe the expedient synthesis of pyrazoles by one-pot three-component condensation of ethyl acetoacetate/acetyl acetone, isoniazide and aryldiazonium salts under solvent free conditions and evaluation of cytotoxicity by Sulforhodamine B assay on three cancer cell lines. The molecular docking studies employing tyrosine kinase were also carried out to evalutae the binding mode of newer pyrazole derivatives. Result: Among ten newly synthesised pyrazolyl analogues, 2-isonicotinoyl-5-methyl-4-(2-(4-nitrophenyl)hydrazono)-2,4-dihydro-3H-pyrazol-3-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines with IC50 value of 0.2-3.4 μM. Conclusion: In summary, our findings suggested that pyrazolyl analogues containing hydrozono/diazenyl pharmacophore are promising scaffold for the development of newer anticancer agents.

Anticolon Cancer Properties of Pyrazole Derivatives Acting through Xanthine Oxidase Inhibition

“…After obtaining interesting results with arylhydrazonopyrazole analogues, different substitutions were made at the phenyl ring for optimizing the template. e analogues 1 and 2 were prepared by using the method described earlier [8].…”

“…Compound 2 was found to be moderately effective, with IC 50 values of 94.2 ± 0.3, 34.6 ± 2.6, and 17.3 ± 0.5 μ M against the MCF-7, HepG2, and HCT-116 cell lines, respectively. Our previous studies have shown that unsubstituted phenyl derivative of aryldiazenyl pyrazole had a poor antiproliferative activity (IC 50 > 100 μ M) against all three cell lines [ 8 ]. This finding indicates that substitution with electron withdrawing groups such as bromo and nitro groups significantly improved the anticancer potential of aryldiazenyl pyrazole derivatives.…”

“…Pyrazolyl analogues 1 and 2 were synthesized using our previously described procedures [ 8 ]. These compounds were evaluated for their in vitro anticancer activity against HepG2, HCT-116, and MCF-7 cell lines by the sulforhodamine B assay (SRB).…”

“…In our previous research, aryldiazo pyrazoles showed a very promising anticancer activity against MCF-7, HepG2, and HCT-116 cell lines. For instance, 4-[2-(4-nitrophenyl)hydrazono]-2-pyrazolin-5-one, as a lead molecule, showed an inhibition of cell proliferation with an IC 50 value in the range of 0.2–3.4 μ M [ 8 ]. Encouraged by these results, we further optimized the lead molecule through different substitutions on the aryl ring.…”

“…Encouraged by these results, we further optimized the lead molecule through different substitutions on the aryl ring. These compounds were synthesized using our previously developed rapid one-pot three-component condensation method for the synthesis of pyrazolyl analogues [ 8 ] and then evaluated the resulting molecules for their anticancer potential.…”