Synthesis, DFT study, molecular docking and insecticidal evaluation of some pyrazole-based tetrahydropyrimidine derivatives

Halim, Karema N. M.; Ramadan, Sayed K.; Rizk, Sameh A.; El‐Hashash, Maher A.

doi:10.1080/00397911.2020.1720739

Cited by 28 publications

(7 citation statements)

References 33 publications

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“…11 01 608, Loja, Ecuador. 3 Departamento de Química y Ciencias Exactas, Universidad Técnica Particular de Loja, San Cayetano Alto s/n, C.P. 11 01 608, Loja, Ecuador.…”

Section: Abbreviationsunclassified

“…Nitrogen-containing rings play an especially important role in drug development because of their wide variety of therapeutic and pharmacological properties [1]. Pyrazoles and their derivatives have attracted particular attention because they have a wide variety of biological activities [2,3], and several drugs currently on the market, have the pyrazole ring as the key structural motif [4]. Some pyrazole derivatives have been demonstrated to be cytotoxic on several human cell lines [5][6][7][8], and, at this time, several drugs that have pyrazoles in their structure have been approved for the treatment of different types of cancer (see Fig.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Background Pyrazoles 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. Results 4,4ʹ-(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. Conclusion Several 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.

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“…11 01 608, Loja, Ecuador. 3 Departamento de Química y Ciencias Exactas, Universidad Técnica Particular de Loja, San Cayetano Alto s/n, C.P. 11 01 608, Loja, Ecuador.…”

Section: Abbreviationsunclassified

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…A chemical proof for structure 6 is gained by preparing an authentic sample through Bignilli condensation of 1 with pentan‐2,4‐dione and thiourea. [ 2 ] Condensation of chloropyrimidine 3 with aminoacetic acid in boiling acetic acid containing anhydrous sodium acetate furnished the N ‐pyrimidinylglycine derivative 7 . However, fusion of 3 with 4‐aminoacetophenone in an oil bath afforded the pyrimidine derivative 8 as brown crystals.…”

Section: Resultsmentioning

confidence: 99%

“…1-(7-(1,3-Diphenyl-1H-pyrazol-4-yl)-5-methyl-3-phenyl-[1,2,4]triazolo[4,3-a] pyrimidin-6-yl)ethan-1-one(10) A mixture of hydrazinopyrimidine 4 (1.16 g, 3 mmol) and benzaldehyde (0.32 g, 3 mmol) was heated in an oil bath at 180 C-190 C for 3 hours. The reaction mixture was allowed to stand at ambient temperature.…”

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confidence: 99%

Straightforward synthesis, antiproliferative screening, and density functional theory study of some pyrazolylpyrimidine derivatives

Halim

Rizk

El‐Hashash

et al. 2020

Journal of Heterocyclic Chem

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Tetrahydropyrimidinone derivative was synthesized through one‐pot three components condensation of 1,3‐diphenylpyrazole‐4‐carbaldehyde with pentan‐2,4‐dione and urea under Biginelli reaction conditions. The corresponding chloro‐ and hydrazino derivatives were synthesized and utilized for the construction of some valuable N‐heterocycles encompassing both pyrazole and pyrimidine cores, such as triazolopyrimidine, tetrazolopyrimidine, pyrazole, and pyrazolone derivatives through condensation with nitrogen nucleophiles and carbon electrophiles. The antiproliferative activity evaluation of the synthesized compounds against four human carcinoma cell lines namely, liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT‐116) cell lines revealed that some of them provided significant potency, as well as the density‐functional theory (DFT) was studied. The permeability of various hydrophilic and hydrophobic synthesized compounds across both normal and cancer cells is confirmed via DFT simulation in which the much higher permeability through aquaporin channels revealed the selective cytotoxicity toward cancer cells.

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“…Considering its large pharmacological scope, substituted pyrazole skeleton is one of the worthy structure fragments in the synthetic and medicizznal chemistry, such as anti‐influenza, [ 1,2 ] antiviral, [ 3–6 ] anticancer, [ 7–12 ] anti‐inflammatory, [ 13,14 ] antitubercular, antiangiogenic, [ 15,16 ] antimicrobial, antioxidant, antidepressant, and insecticidal activities. [ 17–21 ] Moreover, the pyrazole ring is considered as an auspicious skeleton providing fair anti‐CDK2 (cyclin‐dependent kinases) behavior with selective and low toxic effects, for example, PNU‐292137 and ethyl 4‐amino‐1 H ‐pyrazole‐3‐carboxylate [ 22 ] (Figure 1). Many of them have been subjected to in vivo efficacy, preclinical and clinical studies.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, antiproliferative activity, and molecular docking of some N‐heterocycles bearing a pyrazole scaffold against liver and breast tumors

Ramadan

El‐Ziaty

Ali

2020

Journal of Heterocyclic Chem

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A new series of some 1,3‐diphenylpyrazole‐based heterocycles were constructed from 2‐cyano‐3‐(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)propenoyl chloride (1). The titled acid chloride was submitted to react with mono‐nucleophilic reagents, including oxygen, sulfur, or nitrogen, to afford new acrylate, thioacrylate, and acrylamide derivatives, respectively. Meanwhile, condensation of 1 with some 1,2‐ and 1,3‐binucleophiles led to the construction of oxadiazepine, pyridopyrimidine, and thiadiazolopyrimidine derivatives (16, 18, 20, 23). In turn, two benzoxazinone derivatives (27, 28) were synthesized upon treating 1 with substituted anthranilic acids followed by heating with acetic anhydride. The antiproliferative activity of the compounds developed against two tumors (HePG2 and MCF7) was evaluated. Compounds 4, 6, 11, 25, and 26 exhibited strong activity and compounds 3, 5, 16, 18, 27, and 28 exhibited moderate activity. A molecular modeling study was conducted by utilizing molecular modeling environment to test the binding free energies of the studied compounds toward human cyclin‐dependent kinase 2. The compounds, 4, 25, and 26, displayed the best docking score. The orientation and hydrogen bond pattern of these compounds in the active site correspond to that of PNU‐292137, which had been approved as a selective CDK2 inhibitor.

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Synthesis, DFT study, molecular docking and insecticidal evaluation of some pyrazole-based tetrahydropyrimidine derivatives

Cited by 28 publications

References 33 publications

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

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

Straightforward synthesis, antiproliferative screening, and density functional theory study of some pyrazolylpyrimidine derivatives

Synthesis, antiproliferative activity, and molecular docking of some N‐heterocycles bearing a pyrazole scaffold against liver and breast tumors

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