Efficient synthesis and antitumor evaluation of 4-aminomethyl-N-arylpyrazoles: Discovery of potent and selective agents for ovarian cancer

Silva, Michael J. V. da; Jacomini, Andrey P.; Figueiredo, Mariana C.; Back, Davi F.; Foglio, Mary Ann; Ruiz, Ana Lúcia T. G.; Paula, Fávero Reisdorfer; Rosa, Fernanda A.

doi:10.1016/j.bmc.2020.115835

Cited by 4 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We started our investigation by a one-pot synthesis of 3carboxyethyl-4-[(aryl)aminomethyl]-5-arylisoxazoles 2(aa-ac)-2(da-dc) from β-enamino diketones 1 a-d. To this, we followed the recently reported methodologies by our research group (Scheme 2). [24][25][26] Gratifyingly, this reaction provided 12 new 4aminomethyl isoxazoles 2 with high regioselectivity. All sub-strates 1 a-d lead to the desired product with moderate to good yields (35-83 %) (Scheme 2).…”

Section: Chemistrymentioning

confidence: 91%

Synthesis and Antiprotozoal Profile of 3,4,5‐Trisubstituted Isoxazoles

et al. 2021

View full text Add to dashboard Cite

A series of 60 4‐aminomethyl 5‐aryl‐3‐substituted isoxazoles were synthesized by an efficient method and evaluated in vitro against Leishmania amazonensis and Trypanosoma cruzi , protozoa that cause the neglected tropical diseases leishmaniasis and Chagas disease, respectively. Thirteen compounds exhibited a selective index greater than 10. The series of 3‐ N ‐acylhydrazone isoxazole derivatives bearing the bithiophene core exhibited the best antiparasitic effects.

show abstract

Section: Chemistrymentioning

confidence: 91%

Synthesis and Antiprotozoal Profile of 3,4,5‐Trisubstituted Isoxazoles

et al. 2021

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Chemistrymentioning

confidence: 99%

“…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).…”

Section: Chemistrymentioning

confidence: 99%

“…Scheme 1: Synthesis of target pyranopyrazoles and pyrazolone derivatives (18)(19)(20)(21)(22)(23) The history of gold complexes as homogeneous catalysts indicates a very successful and attractive area of chemistry [32][33][34]. In a preliminary plan, our group tested the action of gold (III) chloride hydrate reagent on aryl pyrano[2,3-c]pyrazole-5-carbo-nitrile (18), in ethanol containing few drops of triethylamine; the product was 4-bromobenzylidenepyrazol-5(4H)-one (21) in low yield as red crystals, rather than the gold complex (24), Scheme 2.…”

Section: Chemistrymentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Musa

Ihmaid

Hughes

et al. 2023

Journal of Biomolecular Structure and Dynamics

View full text Add to dashboard Cite

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9)Overexpression is associated with a lower overall survival rate in breast cancer patients.Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, 1 H NMR, 13 C NMR, 13 C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC50 at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC50 values of 0.143 and 0.121 µM, respectively. Both molecular docking experiments and molecular dynamics simulation were also conducted for further interpretations of the in vitro obtained results.

show abstract