-
International Journal of Nanomedicine 2019It is well known that the grafted multiwalled carbon nanotubes (MWCNTs) have antibacterial activity and lower cytotoxicity. Moreover, pyrazole derivatives have a broad...
INTRODUCTION
It is well known that the grafted multiwalled carbon nanotubes (MWCNTs) have antibacterial activity and lower cytotoxicity. Moreover, pyrazole derivatives have a broad spectrum of biological activity due to their fertile template for many medicinal drugs. On view of these findings we report herein the hybridization between MWCNTs and some pyrazole derivatives as antibacterial agents.
MATERIALS AND METHODS
Pyrazole and pyrazolone derivatives were grafted onto the surface of carboxylated MWCNTs via the reaction of carboxylated MWCNTs and the diazonium salts of pyrazoles and pyrazolones using mixed acid treatment. The insertion of the pyrazole and pyrazolone moieties was characterized by Fourier transform infrared (FTIR) spectroscopy, energy dispersion spectroscopy, transmission electron microscopy, X-ray diffraction and thermogravimetric (TGA).
RESULTS
The results indicate that pyrazole and pyrazolone moieties successfully attached on carboxylated MWCNTs surface. The neat pyrazole and pyrazolone derivatives and their corresponding carbon nanotubes were tested against , and bacteria, and fungi. The results showed that the grafted carbon nanotubes of pyrazole and pyrazolone derivatives have better antimicrobial activity than the neat pyrazole and pyrazolone derivatives. The molecular docking studies were performed on the most potent antimicrobial compounds to investigate the existence of the interactions between the most active inhibitors and Farnesyl pyrophosphate synthase (FPPS).
CONCLUSION
The surface of the carboxylated MWCNTs was successfully grafted with some pyrazole derivatives. The antibacterial activity was investigated for the newly synthesized compounds and indicated that the grafted MWCNTs have good antibacterial activity toward some pathogenic types of bacteria.
Topics: Anti-Bacterial Agents; Bacteria; Catalytic Domain; Fungi; Ligands; Microbial Sensitivity Tests; Molecular Docking Simulation; Nanotubes, Carbon; Pyrazoles; Spectroscopy, Fourier Transform Infrared; Thermogravimetry; X-Ray Diffraction
PubMed: 31686804
DOI: 10.2147/IJN.S182699 -
Canadian Medical Association Journal Aug 1976Pharmaceutical manufacturers producing or distributing drugs in Canada were surveyed between December 1974 and March 1975 to determine which of their products contained...
Pharmaceutical manufacturers producing or distributing drugs in Canada were surveyed between December 1974 and March 1975 to determine which of their products contained tartrazine, a pyrazole aniline dye. A list of some 580 drug products of the 156 manufacturers who responded is presented for aid in managing the tartrazine-sensitive patients.
Topics: Aniline Compounds; Coloring Agents; Drug Hypersensitivity; Humans; Pyrazoles; Technology, Pharmaceutical
PubMed: 953903
DOI: No ID Found -
Molecules (Basel, Switzerland) Jul 2023The altered activation or overexpression of protein kinases (PKs) is a major subject of research in oncology and their inhibition using small molecules, protein kinases... (Review)
Review
The altered activation or overexpression of protein kinases (PKs) is a major subject of research in oncology and their inhibition using small molecules, protein kinases inhibitors (PKI) is the best available option for the cure of cancer. The pyrazole ring is extensively employed in the field of medicinal chemistry and drug development strategies, playing a vital role as a fundamental framework in the structure of various PKIs. This scaffold holds major importance and is considered a privileged structure based on its synthetic accessibility, drug-like properties, and its versatile bioisosteric replacement function. It has proven to play a key role in many PKI, such as the inhibitors of Akt, Aurora kinases, MAPK, B-raf, JAK, Bcr-Abl, c-Met, PDGFR, FGFRT, and RET. Of the 74 small molecule PKI approved by the US FDA, 8 contain a pyrazole ring: Avapritinib, Asciminib, Crizotinib, Encorafenib, Erdafitinib, Pralsetinib, Pirtobrutinib, and Ruxolitinib. The focus of this review is on the importance of the unfused pyrazole ring within the clinically tested PKI and on the additional required elements of their chemical structures. Related important pyrazole fused scaffolds like indazole, pyrrolo[1,2-b]pyrazole, pyrazolo[4,3-b]pyridine, pyrazolo[1,5-a]pyrimidine, or pyrazolo[3,4-d]pyrimidine are beyond the subject of this work.
Topics: Pyrazoles; Protein Kinase Inhibitors; Antineoplastic Agents; Drug Design; Structure-Activity Relationship; Humans; Animals
PubMed: 37513232
DOI: 10.3390/molecules28145359 -
Molecules (Basel, Switzerland) Feb 2013A series of 2-pyrazolines 5-9 have been synthesized from α,β-unsaturated ketones 2-4. New 2-pyrazoline derivatives 13-15 bearing benzenesulfonamide moieties were then...
A series of 2-pyrazolines 5-9 have been synthesized from α,β-unsaturated ketones 2-4. New 2-pyrazoline derivatives 13-15 bearing benzenesulfonamide moieties were then synthesized by condensing the appropriate chalcones 2-4 with 4-hydrazinyl benzenesulfonamide hydrochloride. Ethyl [1,2,4] triazolo[3,4-c][1,2,4]triazino[5,6-b]-5H-indole-5-ethanoate (26) and 1-(5H-[1,2,4]triazino[5,6-b] indol-3-yl)-3-methyl-1H-pyrazol-5(4H)-one (32) were synthesized from 3-hydrazinyl-5H-[1,2,4]triazino[5,6-b]indole (24). On the other hand ethyl[1,2,4]triazolo[3,4-c][1,2,4]triazino[5,6-b]-5,10-dihydroquinoxaline- 5-ethanoate (27) and 1-(5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxalin-3-yl)-3-methyl-1H-pyrazol-5(4H)-one (33) were synthesized from 3-hydrazinyl-5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxaline (25) by reaction with diethyl malonate or ethyl acetoacetate, respectively. Condensation of 6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde (1') with compound 24 or 25 afforded the corresponding Schiff's bases 36 and 37, respectively. Reaction of the Schiff's base 37 with benzoyl hydrazine or acetic anhydride afforded benzohydrazide derivative 39 and the cyclized compound 40, respectively. Furthermore, the pyrazole derivatives 42-44 were synthesized by cyclization of hydrazine derivative 25 with the prepared chalcones 2-4. All the newly synthesized compounds have been characterized on the basis of IR and 1H-NMR spectral data as well as physical data. Antimicrobial activity against the organisms E. coli ATCC8739 and P. aeruginosa ATCC 9027 as examples of Gram-negative bacteria, S. aureus ATCC 6583P as an example of Gram-positive bacteria and C. albicans ATCC 2091 as an example of a yeast-like fungus have been studied using the Nutrient Agar (NA) and Sabouraud Dextrose Agar (SDA) diffusion methods. The best performance was found for the compounds 16, 17, 19 and 20.
Topics: Anti-Bacterial Agents; Antifungal Agents; Microbial Sensitivity Tests; Nuclear Magnetic Resonance, Biomolecular; Pyrazoles
PubMed: 23449067
DOI: 10.3390/molecules18032683 -
Molecules (Basel, Switzerland) Dec 2019Pyrazoles are known as versatile scaffolds in organic synthesis and medicinal chemistry, often used as starting materials for the preparation of more complex... (Review)
Review
Pyrazoles are known as versatile scaffolds in organic synthesis and medicinal chemistry, often used as starting materials for the preparation of more complex heterocyclic systems with relevance in the pharmaceutical field. Pyrazoles are also interesting compounds from a structural viewpoint, mainly because they exhibit tautomerism. This phenomenon may influence their reactivity, with possible impact on the synthetic strategies where pyrazoles take part, as well as on the biological activities of targets bearing a pyrazole moiety, since a change in structure translates into changes in properties. Investigations of the structure of pyrazoles that unravel the tautomeric and conformational preferences are therefore of upmost relevance. 3(5)-Aminopyrazoles are largely explored as precursors in the synthesis of condensed heterocyclic systems, namely pyrazolo[1,5-a]pyrimidines. However, the information available in the literature concerning the structure and chemistry of 3(5)-aminopyrazoles is scarce and disperse. We provide a revision of data on the present subject, based on investigations using theoretical and experimental methods, together with the applications of the compounds in synthesis. It is expected that the combined information will contribute to a deeper understanding of structure/reactivity relationships in this class of heterocycles, with a positive impact in the design of synthetic methods, where they take part.
Topics: Chemistry, Pharmaceutical; Molecular Structure; Pyrazoles; Pyrimidines; Structure-Activity Relationship
PubMed: 31877672
DOI: 10.3390/molecules25010042 -
International Journal of Molecular... Oct 2023A variety of ribo-, 2'-deoxyribo-, and 5'-norcarbocyclic derivatives of the 8-aza-7-deazahypoxanthine fleximer scaffolds were designed, synthesized, and screened for...
A variety of ribo-, 2'-deoxyribo-, and 5'-norcarbocyclic derivatives of the 8-aza-7-deazahypoxanthine fleximer scaffolds were designed, synthesized, and screened for antibacterial activity. Both chemical and chemoenzymatic methods of synthesis for the 8-aza-7-deazainosine fleximers were compared. In the case of the 8-aza-7-deazahypoxanthine fleximer, the transglycosylation reaction proceeded with the formation of side products. In the case of the protected fleximer base, 1-(4-benzyloxypyrimidin-5-yl)pyrazole, the reaction proceeded selectively with formation of only one product. However, both synthetic routes to realize the fleximer ribonucleoside () worked with equal efficiency. The new compounds, as well as some 8-aza-7-deazapurine nucleosides synthesized previously, were studied against Gram-positive and Gram-negative bacteria and . It was shown that 1-(β-D-ribofuranosyl)-4-(2-aminopyridin-3-yl)pyrazole () and 1-(2',3',4'-trihydroxycyclopent-1'-yl)-4-(pyrimidin-4(3H)-on-5-yl)pyrazole () were able to inhibit the growth of mc2 155 by 99% at concentrations (MIC) of 50 and 13 µg/mL, respectively. Antimycobacterial activities were revealed for 4-(4-aminopyridin-3-yl)-1H-pyrazol () and 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-4-(4-benzyloxypyrimidin-5-yl)pyrazole (). At concentrations (MIC) of 40 and 20 µg/mL, respectively, the compounds resulted in 99% inhibition of growth.
Topics: Humans; Anti-Bacterial Agents; Nucleosides; Gram-Negative Bacteria; Gram-Positive Bacteria; Mycobacterium tuberculosis; Tuberculosis; Pyrazoles; Microbial Sensitivity Tests; Structure-Activity Relationship
PubMed: 37895100
DOI: 10.3390/ijms242015421 -
ChemMedChem Sep 2020Small-molecule heterocycles bearing orthogonal functionality have the potential to deliver diverse structural motifs that aid the drug-discovery effort. This work...
Small-molecule heterocycles bearing orthogonal functionality have the potential to deliver diverse structural motifs that aid the drug-discovery effort. This work highlights how a readily assembled N-hydroxyethyl pyrazole trifluoroborate offers rapid access to architecturally distinct 5-6-6- and 5-7-6-fused tricyclic compounds. This chemistry is not only amenable to single compound synthesis, but also to high-throughput experimentation. It gives easy access to diverse compound arrays with various physicochemical and ADME profiles by fully automated library synthesis. The combination of the high-throughput experimentation with rapid testing of the compounds in an integrated physicochemical and ADME profiling workflow allows accelerated design of novel lead compounds in drug-discovery projects.
Topics: Automation; Drug Design; Heterocyclic Compounds; Molecular Structure; Pyrazoles; Small Molecule Libraries
PubMed: 32427423
DOI: 10.1002/cmdc.202000187 -
Molecules (Basel, Switzerland) May 2022The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs....
The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute (NCI) database, together with their growth inhibition effects (GI%) on the NCI's panel of 60 cancer cell lines. The structures of these derivatives were analyzed based on the compounds' averages of GI% values across NCI-60 cell lines and the averages of the values for the outlier cells. The distribution and the architecture of the Bemis-Murcko skeletons were analyzed, highlighting the impact of certain scaffold structures on the anti-proliferative effect's potency and selectivity. The drug-likeness, chemical reactivity and promiscuity risks of the compounds were predicted using AMDETlab. The pyrazole ring proved to be a versatile scaffold for the design of anticancer drugs if properly substituted and if connected with other cyclic structures. The 1,3-diphenyl-pyrazole emerged as a useful scaffold for potent and targeted anticancer candidates.
Topics: Antineoplastic Agents; Cell Line, Tumor; Pyrazoles
PubMed: 35630776
DOI: 10.3390/molecules27103300 -
Molecules (Basel, Switzerland) Jun 2022An efficient synthetic route to construct diverse pyrazole-based chalcones from 1-phenyl-1-pyrazol-3-ols bearing a formyl or acetyl group on the C4 position of pyrazole...
An efficient synthetic route to construct diverse pyrazole-based chalcones from 1-phenyl-1-pyrazol-3-ols bearing a formyl or acetyl group on the C4 position of pyrazole ring, employing a base-catalysed Claisen-Schmidt condensation reaction, is described. Isomeric chalcones were further reacted with -hydroxy-4-toluenesulfonamide and regioselective formation of 3,5-disubstituted 1,2-oxazoles was established. The novel pyrazole-chalcones and 1,2-oxazoles were characterized by an in-depth analysis of NMR spectral data, which were obtained through a combination of standard and advanced NMR spectroscopy techniques.
Topics: Chalcone; Chalcones; Magnetic Resonance Spectroscopy; Oxazoles; Pyrazoles
PubMed: 35744875
DOI: 10.3390/molecules27123752 -
Molecules (Basel, Switzerland) Dec 2023Among well-studied and actively developing compounds are polyoxometalates (POMs), which show application in many fields. Extending this class of compounds, we introduce...
Among well-studied and actively developing compounds are polyoxometalates (POMs), which show application in many fields. Extending this class of compounds, we introduce a new subclass of polyoxometal clusters (POMCs) [MoO(μ-L)] (L = pyrazolate (pz) or triazolate (1,2,3-trz or 1,2,4-trz)), structurally similar to POM, but containing binuclear MoO clusters linked by bridging oxo- and organic ligands. The complexes obtained by ampoule synthesis from the binuclear cluster [MoO(CO)(HO)] in a melt of an organic ligand are soluble and stable in aqueous solutions. In addition to the detailed characterization in solid state and in aqueous solution, the biological properties of the compounds on normal and cancer cells were investigated, and antiviral activity against influenza A virus (subtype H5N1) was demonstrated.
Topics: Water; Models, Molecular; Molybdenum; Influenza A Virus, H5N1 Subtype; Triazoles; Pyrazoles; Antiviral Agents
PubMed: 38138569
DOI: 10.3390/molecules28248079