54711-21-6Relevant articles and documents
Synthesis of some novel N5-sulfonylated and N1-alkyated pyrazole derivatives and their antimicrobial activity in conjunction with molecular docking study
Metwally, Nadia H.,Mohamed, Mona S.,Ragab, Eman A.
, (2020)
Some novel N5-sulfonylated 4 were synthesized via sulfonylation of 5-amino-1H-pyrazole derivative 1 with arylsulfonyl chlorides. On the other hand, N1-alkylated pyrazoles 7 and 10 were synthesized through alkylation of compound 1 with each of chloroacetamides and ethylchloroacetate under different conditions. Condensation of compounds 4 and 7 with different aromatic aldehydes furnished the corresponding arylidene derivatives. In spite of, condensation of 10 with aromatic aldehydes afforded the 2-(5-amino-2-aryl-1H-pyrazol-1-yl)acetic acid. The structure of the newly synthesized compounds was elucidated by elemental analyses and spectral data. Also, the suggested mechanisms for their formation were studied. Additionally, some selected new compounds were screened against antimicrobial activity. Compound 7c exhibited a higher activity against Candida albicans (inhibition zone diameter [IZD] = 31.3 ± 0.6 mm) than the standard antibiotic Nystatin (IZD = 21 ± 0.5 mm). Also, compound 7c showed minimum inhibitory concentration = 125 and 250 μg/mL against Klebsiella pneumonia and Staphylococcus aureus, respectively. Molecular docking study also was carried out for compound 7c.
Design, synthesis, anticancer evaluation, molecular docking and cell cycle analysis of 3-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine derivatives as potent histone lysine demethylases (KDM) inhibitors and apoptosis inducers
Metwally, Nadia Hanafy,Mohamed, Mona Said,Ragb, Eman Ali
, (2019)
A novel series of pyrazolo[1,5-a]pyrimidines were synthesized and proved by their spectral and elemental analysis, some elected of the newly synthesized compounds were examined for their cytotoxic activity employing MTT assay on two cancer cell lines (Breast and Hela cancers). Compounds 5, 7e and 7i showed the higher cytotoxicity against two cancer cell lines with (IC50 = 13.91 ± 1.4 and 22.37 ± 1.8 μM/L), (IC50 = 6.56 ± 0.5 and 8.72 ± 0.9 μM/L) and (IC50 = 4.17 ± 0.2 and 5.57 ± 0.4 μM/L) for two cancer cell lines breast and hela respectively, using doxorubicin as a reference drug. The most potent cytotoxic active compounds 5, 7e and 7i presented inhibitory activity against KDM (histone lysine demethylases) with IC50 = 4.05, 1.91 and 2.31 μM, respectively. The most potent KDM inhibitor 7e (IC50 = 1.91 μM) showed to cause cell cycle arrest at G2/M phase by 4 folds than control and induce total apoptotic effect by 10 folds more than control. In silico studies performed on the more potent cytotoxic active compounds 5, 7e and 7i included lipinisk's rule of five. Moreover, molecular docking study was utilized to explore the binding mode of the most active compounds to the target enzyme (PDB-ID: 5IVE). Also, some bioinformatics studies were carried out for compounds 7e and 7i using Swiss ADME (Swiss Institute of bioinformatics 2018).
Pyrazolo-oxo-diaza compound as BTK inhibitor
-
Paragraph 0117-0120, (2021/03/24)
The invention provides a pyrazolo-oxo-diaza compound with a remarkable inhibition effect on Bruton's tyrosine protein kinase (BTK) or a hydrate, a solvate, a prodrug, a stereoisomer or a tautomer of pharmaceutically acceptable salt of the pyrazolo-oxo-diaza compound. The invention also provides a process for preparing the compound of the invention and an intermediate compound which can be used inthe process. The compound provided by the invention can be used for preparing medicines for treating diseases related to disorder or imbalance of activity of Bruton's tyrosine kinase (BTK).
Synthesis, anticancer evaluation, CDK2 inhibition, and apoptotic activity assessment with molecular docking modeling of new class of pyrazolo[1,5-a]pyrimidines
Metwally, Nadia Hanafy,Mohamed, Mona Said,Deeb, Emad Abdullah
, p. 5027 - 5060 (2021/08/31)
2-Cyanopyrazolo[1,5-a]pyrimidine derivative 3 reacted with some aromatic aldehydes, arenediazonium salts, hydrazine hydrate, and guanidine hydrochloride to create a series of novel pyrazolo[1,5-a]pyrimidine derivatives. Spectroscopic data confirmed the structure of the newly synthesized compounds. Some target compounds were tested in vitro for anticancer efficacy against three cancer cell lines: HepG-2, MCF-7, and Hela. On the most efficient anticancer compounds 6b,c, 6f, and 6h,i, the CDK-2 enzyme was evaluated. Using the HepG-2 cancer cell line, compounds 6b and 6i demonstrated the most effective inhibitory activity against CDK-2, with IC50 values of 0.199 ± 0.005?μg/ml and IC50 = 0.206 ± 0.007?μg/ml, respectively, compared to Dinaciclib and Roscovitine, which had IC50 values of 0.021 ± 0.002 and 0.230 ± 0.007?μg/ml, respectively. In cell cycle assay, compounds 6b, 6f and 6i arrest cell cycle at G2/M, G1/S and G2/M phases, respectively. Compound 6f has a stronger apoptosis induction effect (27.82%) than compounds 6b (7.92%) and 6i (19.21%). Also, silico studies (Molecular docking and Lipinski’s rules) for compounds 6b, 6f and 6i were carried out. Graphic abstract: [Figure not available: see fulltext.]
