Design, synthesis and biological evaluation of isoxazole bearing N-Arylpyrazole derivatives as anticancer agents

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro , and in silico mechanistic investigations

“…pyrano [2,3-c]pyrazole derivatives (18)(19)(20) were easily attained in a satisfactory yield by a one-pot, three-component reaction of precursor phenylpyrazole (15), malononitrile (16) with three aromatic aldehydes (17) in an ethanolic solution containing a catalytic amount of piperidine. Alternatively, the target compounds (18)(19)(20) were also obtained by condensation of precursor phenylpyrazolone (15) with the same set of aldehydes (17) to afford the benzylidene-pyrazolone (21)(22)(23). These latter were lastly allowed to react with malononitrile (16) to give our target pyranopyrazoles (18)(19)(20).…”

“…Alternatively, the target compounds (18)(19)(20) were also obtained by condensation of precursor phenylpyrazolone (15) with the same set of aldehydes (17) to afford the benzylidene-pyrazolone (21)(22)(23). These latter were lastly allowed to react with malononitrile (16) to give our target pyranopyrazoles (18)(19)(20).…”

“…The N-phenylpyrazoles 11 and 12 exhibited good growth inhibitory activity against breast cancer cells with GI50 values of 72.44 µM and 74.15 µM, respectively, with acceptable selectivity indices. They also showed good potential to interact with the crucial amino acid residues of the CDK target in the performed docking experiments [19]. On the other hand, numerous N-arylpyrazoles have been recently developed and presented good inhibitory activity against certain subtypes of CDKs [23,24].…”

“…Arylpyrazoles are active motifs that possess various biological activities including anti-inflammatory [15], anticonvulsant [16,17], anticancer [18][19][20], antiviral [21], and neuroprotective activity [22]. In the present year, a series of N-arylpyrazoles has been synthesized and estimated as potential anticancer candidates for breast (MCF-7 & MDA MB-231), lung (A549), prostrate (DU-145) cancers.…”

“…Among the synthesized arylpyrazoles, compounds 9 and 10 (Figure 1) demonstrated more potent activity than etoposide. In particular, compound 10 showed the best efficiency compared to all other derivatives [IC50 = 0.31 µM (MCF-7), 0.37 µM (MDA MB-231), 0.47 µM (A549), and 0.19 µM (DU-145)] [19]. As well, many N-arylpyrazole derivatives have been synthesized through one-pot two-steps consecutive methodology.…”