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Bioorganic Chemistry Apr 2020Pyrazole is a five-membered aromatic heterocyclic ring with two adjacent nitrogen atoms CHNH.The presence of this nucleus in pharmacological agents of various... (Review)
Review
Pyrazole is a five-membered aromatic heterocyclic ring with two adjacent nitrogen atoms CHNH.The presence of this nucleus in pharmacological agents of various therapeutic categories gifts a broad spectrum of biological activities and pharmaceuticals that contain pyrazole like celecoxib (anti-inflammatory), CDPPB (antipsychotic), Rimonabant (anti-obesity), Difenamizole, (Analgesic), Betazole (H2 receptor agonist), Fezolamide (Antidepressant), etc… The pharmacological potential of the pyrazole fraction is proved in many publication where they synthesized and evaluated pyrazoles against several biological agents. The aim of this article review is to survey recent works linking pyrazole structures to anticancer activities corresponding to 9 different type of cancer.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chemistry Techniques, Synthetic; Drug Design; Drug Discovery; Drug Screening Assays, Antitumor; Humans; Neoplasms; Pyrazoles
PubMed: 32120072
DOI: 10.1016/j.bioorg.2019.103470 -
Future Medicinal Chemistry Jan 2018Benzothiazole and pyrazoles are two important pharmacophores, the activity can be enhanced by conjugating them. Here, two novel series of the pyrazole-conjugated...
AIM
Benzothiazole and pyrazoles are two important pharmacophores, the activity can be enhanced by conjugating them. Here, two novel series of the pyrazole-conjugated benzothiazole derivatives were synthesized.
RESULTS
Synthesized compounds were characterized by Fourier-transform infrared, LC-MS, H NMR and C NMR spectroscopic techniques. Synthesized compounds exhibited moderate antimicrobial, antioxidant and excellent anti-TB activities. In in vitro anti-TB activity, 4d and 4e exhibited 1.6 μg/ml minimum inhibitory concentration value. In order to rationalize the anti-TB activity, molecular docking studies were carried out and they were correlated with the in vitro results.
CONCLUSION
Compounds containing electron donating groups show the promising antimicrobial and antioxidant activities, compounds with CH and Cl substitution show excellent anti-TB activity. Synthesized molecules may become potential candidates for the clinical trials.
Topics: Antioxidants; Antitubercular Agents; Benzothiazoles; Cell Survival; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Pyrazoles; Structure-Activity Relationship; Tuberculosis
PubMed: 29235357
DOI: 10.4155/fmc-2017-0138 -
Future Medicinal Chemistry Sep 2023There has been an increasing trend in the design of novel pyrazole derivatives for desired biological applications. For a cost-effective strategy, scientists have... (Review)
Review
There has been an increasing trend in the design of novel pyrazole derivatives for desired biological applications. For a cost-effective strategy, scientists have implemented various computational drug design tools to go hand in hand with experiments for the design and discovery of potentially effective pyrazole-based therapeutics. This review highlights the milestones of pyrazole-containing inhibitors and the use of molecular modeling techniques in conjunction with experimental studies to provide a view of the binding mechanism of these compounds. The review focuses on the established targets that play a key role in cancer therapy, including proteins involved in tubulin polymerization, carbonic anhydrase and tyrosine kinase. Overall, using both experimental and computational methods in drug design represents a promising approach to cancer therapy.
Topics: Humans; Molecular Structure; Antineoplastic Agents; Models, Molecular; Pyrazoles; Neoplasms; Structure-Activity Relationship; Molecular Docking Simulation
PubMed: 37772542
DOI: 10.4155/fmc-2023-0142 -
Archiv Der Pharmazie Feb 2022Novel series of pyrazolo[3,4-b]pyridines 9a-j and 14a-f were prepared via a one-pot three-component reaction. Compounds 9a-j were synthesized by the reaction of...
Novel series of pyrazolo[3,4-b]pyridines 9a-j and 14a-f were prepared via a one-pot three-component reaction. Compounds 9a-j were synthesized by the reaction of 3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-5-amine (4) with benzoyl acetonitriles 3a,b and aldehydes 5a-e, whereas the spiro derivatives 14a-f were synthesized by the reaction of pyrazole derivative 4 with 3a-c and indoline-2,3-diones 10a,b. Screening of the antiproliferative activity of 9a-j and 14a-f revealed that 14a and 14d were the most potent analogues against HepG2 and HeLa cells, with IC = 4.2 and 5.9 μM, respectively. Moreover, compounds 9c and 14a could promote cell cycle disturbance and apoptosis in HepG2 cells, as evidenced by DNA flow cytometry and Annexin V-FITC/PI assays. Cell cycle analysis of 9c and 14a indicated a reduction in HepG2 cells in the G1 phase, with arrest in the S phase and the G2/M phase, respectively. Also, 9c and 14a are good apoptotic inducers in the HepG2 cell line. Furthermore, compounds 9h and 14d stood out as the most efficient antiproliferative agents in the NCI 60-cell line panel screening, with mean GI % equal to 60.3% and 55.4%, respectively. Additionally, 9c, 9h, 14a, and 14d showed good inhibitory action against the cellular pathway regulator p38α kinase, with IC = 0.42, 0.41, 0.13, and 0.64 μM, respectively. A docking study was carried out on the p38α kinase active site, showing a binding mode comparable to that of reported p38 mitogen-activated protein kinase inhibitors. These newly discovered pyrazolo[3,4-b]pyridines could be considered as potential candidates for the development of newly targeted anticancer agents.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; HeLa Cells; Hep G2 Cells; Humans; Inhibitory Concentration 50; Mitogen-Activated Protein Kinase 14; Molecular Docking Simulation; Pyrazoles; Pyridines; Structure-Activity Relationship
PubMed: 34796536
DOI: 10.1002/ardp.202100302 -
Medicinal Chemistry (Shariqah (United... 2022Pyrazole is a component of a diversity of bioactive heterocyclic congeners with a broad-spectrum range of biological and pharmacological uses. Designing novel pyrazole...
BACKGROUND
Pyrazole is a component of a diversity of bioactive heterocyclic congeners with a broad-spectrum range of biological and pharmacological uses. Designing novel pyrazole and its analogues, revealing new routes for synthesizing this nucleus, exploring various potencies of that heterocycles, and looking for possible applications of pyrazoles are all becoming more important due to their numerous potential applications.
OBJECTIVES
Pyrazole scaffolds have been proven to be successful as anti-viral and anti-inflammatory therapeutics against multiple targets like HSV-1, NNRTI, H1N1, CoX-1, and CoX-2. Due to this miscellany in the biotic area, this moiety has engrossed the consideration of many scientists to study chemistry and pharmacological profile.
RESULTS
The review encompasses pyrazole having various scaffolds with multiple biological activities and attempts have also been made to correlate their structure-activity relationship. Multiple pyrazole correspondents have been synthesized as lead molecules and performed valuation for their actions.
CONCLUSION
The incorporation of pyrazole with other pharmacophores in the molecule might lead to novel potent therapeutic agents that will further help in designing potent lead molecules.
Topics: Anti-Inflammatory Agents; Antiviral Agents; Drug Design; Influenza A Virus, H1N1 Subtype; Pyrazoles; Structure-Activity Relationship
PubMed: 35410619
DOI: 10.2174/1573406418666220410181827 -
Chemical Communications (Cambridge,... Apr 2022Indazole and pyrazole are renowned as a prodigious class of heterocycles having versatile uses in medicinal as well as industrial chemistry. Considering sustainable... (Review)
Review
Indazole and pyrazole are renowned as a prodigious class of heterocycles having versatile uses in medicinal as well as industrial chemistry. Considering sustainable approaches, recently, photocatalysis has become an indispensable tool in organic chemistry due to its application for the activation of small molecules and the use of a clean energy source. In this review, we have highlighted the use of metal-based photocatalysts, organic photoredox catalysts, energy transfer photocatalysts and electron-donor-acceptor complexes in the functionalization of indazole and pyrazole. This perspective is arranged based on the types of functionalization reactions on indazole and pyrazole. A detailed discussion regarding the reaction mechanism of each reaction is given to provide a comprehensive guide to the reader. Finally, a summary of existing challenges and the future outlook towards the development of efficient photocatalytic methods for functionalization of these heterocycles is also presented.
Topics: Catalysis; Indazoles; Light; Pyrazoles
PubMed: 35294515
DOI: 10.1039/d2cc00002d -
Bioorganic & Medicinal Chemistry Feb 2023Deregulation of cyclin-dependent kinase 2 (CDK2) and its activating partners, cyclins A and E, is associated with the pathogenesis of a myriad of human cancers and with...
Deregulation of cyclin-dependent kinase 2 (CDK2) and its activating partners, cyclins A and E, is associated with the pathogenesis of a myriad of human cancers and with resistance to anticancer drugs including CDK4/6 inhibitors. Thus, CDK2 has become an attractive target for the development of new anticancer therapies and for the amelioration of the resistance to CDK4/6 inhibitors. Bioisosteric replacement of the thiazole moiety of CDKI-73, a clinically trialled CDK inhibitor, by a pyrazole group afforded 9 and 19 that displayed potent CDK2-cyclin E inhibition (K = 0.023 and 0.001 μM, respectively) with submicromolar antiproliferative activity against a panel of cancer cell lines (GI = 0.025-0.780 μM). Mechanistic studies on 19 with HCT-116 colorectal cancer cells revealed that the compound reduced the phosphorylation of retinoblastoma at Ser807/811, arrested the cells at the G2/M phase, and induced apoptosis. These results highlight the potential of the 2-anilino-4-(1-methyl-1H-pyrazol-4-yl)pyrimidine series in developing potent and selective CDK2 inhibitors to combat cancer.
Topics: Humans; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinases; Antineoplastic Agents; Neoplasms; Pyrimidines; Pyrazoles
PubMed: 36706608
DOI: 10.1016/j.bmc.2023.117158 -
Mini Reviews in Medicinal Chemistry 2019Bis-heterocycles especially those containing pyrazole moiety display much better antibacterial activity than mono heterocycles.
BACKGROUND
Bis-heterocycles especially those containing pyrazole moiety display much better antibacterial activity than mono heterocycles.
OBJECTIVE
Herein, we synthesised a series of new bis-pyrazoles and investigated their antimicrobial agents.
METHODS
A novel series of bis-pyrazole derivatives have been synthesized in good yield by coupling reaction of cyanoacetic acid {4-[(2-cyano-acetyl)-hydrazonomethyl]-benzylidene}-hydrazide with a number of diazonium salts of aromatic amines in DMF in the presence of NaOH. Refluxing of the produced hydrazones with hydrazine-hydrate in ethanolic solution afforded the respective bis-pyrazoles. On the other hand, the reaction of bis(cyanoacetic acid hydrazide) derivative with a diversity of hydrazonoyl chlorides in dioxane under reflux gave bis-pyrazoles.
RESULTS
The structures of all the products were discussed and assured from all possible spectral data as well as for the elemental analysis. In addition, the results of the antimicrobial activity examination of selected derivatives revealed a high strength of some tested compounds compared to standard bactericides and fungicides utilized. Molecular docking of the newly synthesized compounds into the Enoyl ACP reductase active site supported the in vitro antimicrobial activity. All the tested compounds could fit in the enzyme binding pocket with significant binding affinities (-7.040 to -9.141 Kcal/mol).
CONCLUSION
The good results of the antimicrobial examination of the newly synthesized bis-pyrazoles comprise the considerable evidence of the importance of bis-heterocyclic compounds which encourages us to continue designing and synthesising a novel series with potent biological activity in the future.
Topics: Anti-Bacterial Agents; Antifungal Agents; Aspergillus niger; Dose-Response Relationship, Drug; Geotrichum; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Pyrazoles; Structure-Activity Relationship
PubMed: 30864524
DOI: 10.2174/1389557519666190313095545 -
Medicinal Chemistry (Shariqah (United... 2019We screened a large library of differently decorated imidazo-pyrazole and pyrazole derivatives as possible new antitubercular agents and this preliminary screening...
BACKGROUND
We screened a large library of differently decorated imidazo-pyrazole and pyrazole derivatives as possible new antitubercular agents and this preliminary screening showed that many compounds are able to totally inhibit Mycobacterium growth (>90 %). Among the most active compounds, we selected some new possible hits based on their similarities and, at the same time, on their novelty with respect to the pipeline drugs.
METHODS
In order to increase the potency and obtain more information about structure-activity relationship (SAR), we designed and synthesized three new series of compounds (2a-e, 3a-e, and 4a-l).
CONCLUSION
Performed tests confirmed that both new pyrazoles and imidazo-pyrazoles could represent a new starting point to obtain more potent compounds and further work is now underway to identify the protein targets of this new class of anti-TB agents.
Topics: Animals; Antitubercular Agents; Chlorocebus aethiops; Imidazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyrazoles; Small Molecule Libraries; Structure-Activity Relationship; Vero Cells
PubMed: 29792151
DOI: 10.2174/1573406414666180524084023 -
Mini Reviews in Medicinal Chemistry 2018Pyrazole nucleus is a unique structural scaffold which acts as an interesting template for combinatorial as well as medicinal chemistry. This review presents a detailed... (Review)
Review
Pyrazole nucleus is a unique structural scaffold which acts as an interesting template for combinatorial as well as medicinal chemistry. This review presents a detailed overview on the synthesis, QSAR and pharmacological applications of pyrazole. In addition, it covers most recent reports on structural modifications on pyrazole illustrating vital structural activity relationship.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Antineoplastic Agents; Antioxidants; Enzyme Inhibitors; Humans; Neoplasms; Obesity; Pyrazoles; Quantitative Structure-Activity Relationship
PubMed: 28971774
DOI: 10.2174/1389557517666170927160919