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Molecules (Basel, Switzerland) Aug 2018A novel series of pyrazolyl 1,3,4-thiadiazines ⁻, ⁻, , ⁻, ⁻, and was prepared from the reaction of pyrazole-1-carbothiohydrazide , with...
A novel series of pyrazolyl 1,3,4-thiadiazines ⁻, ⁻, , ⁻, ⁻, and was prepared from the reaction of pyrazole-1-carbothiohydrazide , with 2-oxo-'-arylpropanehydrazonoyl chloride, 2-chloro-2-(2-arylhydrazono)acetate, and 3-bromoacetylcoumarin. Moreover, the regioselective reaction of 5-pyrazolone-1-carbothiohydrazide with 4-substituted diazonium salts and 4-(dimethylamino)benzaldehyde gave the corresponding hydrazones ⁻ and . The newly prepared compounds were characterized by spectroscopy and elemental analysis. Many new synthesized compounds showed considerable antimicrobial activity against tested microorganisms. Hydrazones ⁻ and showed remarkable antibacterial and antifungal activities. 4-(2-(-tolyl)hydrazineylidene)-pyrazole-1-carbothiohydrazide displayed the highest antibacterial and antifungal activities with minimum inhibitory concentration (MIC) values lower than standard drugs chloramphenicol and clotrimazole, in the range of 62.5⁻125 and 2.9⁻7.8 µg/mL, respectively.
Topics: Anti-Infective Agents; Bacteria; Chemistry Techniques, Synthetic; Drug Design; Fungi; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles; Thiadiazines
PubMed: 30134530
DOI: 10.3390/molecules23092092 -
European Journal of Pharmaceutical... Apr 2023Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the... (Review)
Review
Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the development of drug resistance in malaria parasites. The standard treatment for malaria is artemisinin-combination therapy (ACT). Nevertheless, the Plasmodium parasite's extensive resistance to prior drugs and reduced ACT efficiency necessitates novel drug discovery. The progress in discovering novel, affordable, and effective antimalarial agents is significant in combating drug resistance, and the hybrid drug concept can be used to covalently link two or more active pharmacophores that may act on multiple targets. Pyrazole and pyrazoline derivatives are considered pharmacologically necessary active heterocyclic scaffolds that possess almost all types of pharmacological activities. This review summarized recent progress in antimalarial activities of synthesized pyrazole and pyrazoline derivatives. The studies published since 2000 are included in this systematic review. This review is anticipated to be beneficial for future study and new ideas in searching for rational development strategies for more effective pyrazole and pyrazoline derivatives as antimalarial drugs.
Topics: Humans; Antimalarials; Malaria; Pyrazoles; Drug Resistance; Folic Acid Antagonists; Plasmodium falciparum
PubMed: 36563914
DOI: 10.1016/j.ejps.2022.106365 -
Annals of Medicine Dec 2022A series of -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity...
A series of -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity against primary patient-derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds was evaluated against glioma cell lines, with compound exhibiting promising glioma growth inhibitory properties. Compound was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. AKT signalling is one of the main oncogenic pathways in glioma and is often targeted for novel therapeutics. Indeed, AKT2 levels correlated with glioma malignancy and poorer patient survival. Compound inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells and exhibited potent EC against glioblastoma cell lines. Although exhibiting potency against glioma cells, exhibited significantly less cytotoxicity against non-cancerous cells even at fourfold-fivefold the concentration. Herein we establish a novel biochemical kinase inhibitory function for -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles and further report their anti-glioma activity for the first time.KEY MESSAGEAnti-glioma pyrano[2,3-c]pyrazole inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. also displayed PKBβ/AKT2 inhibitory activity. is nontoxic towards non-cancerous cells.
Topics: Glioblastoma; Humans; Proto-Oncogene Proteins c-akt; Pyrazoles
PubMed: 36120909
DOI: 10.1080/07853890.2022.2123559 -
Molecules (Basel, Switzerland) Jul 2022Pyrazole and its derivatives are considered a privileged -heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy... (Review)
Review
Pyrazole and its derivatives are considered a privileged -heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.
Topics: Anti-Bacterial Agents; Antifungal Agents; Chemistry, Pharmaceutical; Molecular Docking Simulation; Pyrazoles; alpha-Glucosidases
PubMed: 35897899
DOI: 10.3390/molecules27154723 -
Molecules (Basel, Switzerland) Jun 2015The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and...
The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Free Radical Scavengers; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles
PubMed: 26060913
DOI: 10.3390/molecules200610468 -
Molecules (Basel, Switzerland) Sep 2020The synthesis of FcC(O)CH(R)C(O)Fc (Fc = Fe(η-CH)(η-CH); R = H, ; Bu, ; CHCH(OCHCH)OMe, ), [M(κ,'-FcC(O)CHC(O)Fc)] (M = Ti, = 3, ; M = Fe, = 3, ; M = BF, = 1, ),...
The synthesis of FcC(O)CH(R)C(O)Fc (Fc = Fe(η-CH)(η-CH); R = H, ; Bu, ; CHCH(OCHCH)OMe, ), [M(κ,'-FcC(O)CHC(O)Fc)] (M = Ti, = 3, ; M = Fe, = 3, ; M = BF, = 1, ), and 1-R'-3,5-Fc-CHN (R' = H, ; Me, ; Ph, ) is discussed. The solid-state structures of , , , , , , and ([TiCl(κ,'-PhC(O)CHC(O)Ph)]) show that and exist in their β-diketo form. Compound crystallizes as a tetramer based on a hydrogen bond pattern, including one central water molecule. The electrochemical behavior of - and - was studied by cyclic and square-wave voltammetry, showing that the ferrocenyls can separately be oxidized reversibly between -50 and 750 mV (-, , -: two Fc-related events; , : six events, being partially superimposed). For complex , Ti-centered reversible redox processes appear at -985 (Ti/Ti) and -520 mV (Ti/Ti). Spectro-electrochemical UV-Vis/NIR measurements were carried out on , and , whereby only showed an IVCT (intervalence charge-transfer) band of considerable strength ( = 6250 cm, = 4725 cm, = 240 L·mol·cm), due to the rigid COB cycle, enlarging the coupling strength between the Fc groups.
Topics: Electrochemistry; Hydrogen Bonding; Ketones; Molecular Conformation; Pyrazoles; Spectrophotometry, Ultraviolet; Spectroscopy, Near-Infrared
PubMed: 33003450
DOI: 10.3390/molecules25194476 -
Molecules (Basel, Switzerland) Jan 2018Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of... (Review)
Review
Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.
Topics: Animals; Anti-HIV Agents; Anti-Inflammatory Agents; Anti-Obesity Agents; Antidepressive Agents; Antipsychotic Agents; Chemistry, Pharmaceutical; Drug Design; Humans; Pyrazoles
PubMed: 29329257
DOI: 10.3390/molecules23010134 -
Molecules (Basel, Switzerland) Jul 2020The pyrazole nucleus has long been known as a privileged scaffold in the synthesis of biologically active compounds. Within the numerous pyrazole derivatives developed... (Review)
Review
The pyrazole nucleus has long been known as a privileged scaffold in the synthesis of biologically active compounds. Within the numerous pyrazole derivatives developed as potential drugs, this review is focused on molecules characterized by a urea function directly linked to the pyrazole nucleus in a different position. In the last 20 years, the interest of numerous researchers has been especially attracted by pyrazolyl-ureas showing a wide spectrum of biological activities, ranging from the antipathogenic activities (bacteria, plasmodium, toxoplasma, and others) to the anticarcinogenic activities. In particular, in the anticancer field, pyrazolyl-ureas have been shown to interact at the intracellular level on many pathways, in particular on different kinases such as Src, p38-MAPK, TrKa, and others. In addition, some of them evidenced an antiangiogenic potential that deserves to be explored. This review therefore summarizes all these biological data (from 2000 to date), including patented compounds.
Topics: Chemistry Techniques, Synthetic; Chemistry, Pharmaceutical; Humans; Pharmaceutical Preparations; Pyrazoles; Structure-Activity Relationship; Urea
PubMed: 32751358
DOI: 10.3390/molecules25153457 -
Expert Opinion on Therapeutic Patents Mar 2012Pyrazolines are well-known and important nitrogen-containing five-membered ring heterocyclic compounds. Various methods have been worked out for their synthesis. Several... (Review)
Review
INTRODUCTION
Pyrazolines are well-known and important nitrogen-containing five-membered ring heterocyclic compounds. Various methods have been worked out for their synthesis. Several pyrazoline derivatives have been found to possess diverse biological properties, which has stimulated research activity in this field.
AREAS COVERED
The present review sheds light on the recent therapeutic patent literature (2000 - 2011) describing the applications of pyrazolines and their derivatives on selected activities. Many of the therapeutic applications of pyrazoline derivatives have been discussed, either in the patent or in the general literature areas in this review. In addition to selected biological data, a wide range of pharmaceutical applications and pharmaceutical compositions are also summarized.
EXPERT OPINION
Pyrazoline derivatives have numerous prominent pharmacological effects, such as antimicrobial (antibacterial, antifungal, antiamoebic, antimycobacterial), anti-inflammatory, analgesic, antidepressant and anticancer. Further pharmacological effects include cannabinoid CB1 receptor antagonists, antiepileptic, antitrypanosomal, antiviral activity, MAO-inhibitory, antinociceptive activity, insecticidal, hypotensive, nitric oxide synthase inhibitor, antioxidant, steroidal and antidiabetic. Lastly, they also effect ACAT inhibition, urotensin II and somatostatin-5 receptors, TGF-β signal transduction inhibitors and neurocytotoxicity inhibitors activities. Many new pyrazoline derivatives have been synthesized and patented, but there are still new aspects to explore and work on.
Topics: Animals; Drug Delivery Systems; Drug Design; Humans; Patents as Topic; Pyrazoles
PubMed: 22397588
DOI: 10.1517/13543776.2012.667403 -
Bioorganic & Medicinal Chemistry Apr 2019A series of N-acyl pyrazoles was examined as candidate serine hydrolase inhibitors in which the active site acylating reactivity and the leaving group ability of the...
A series of N-acyl pyrazoles was examined as candidate serine hydrolase inhibitors in which the active site acylating reactivity and the leaving group ability of the pyrazole could be tuned not only through the nature of the acyl group (reactivity: amide > carbamate > urea), but also through pyrazole C4 substitution with electron-withdrawing or electron-donating substituents. Their impact on enzyme inhibitory activity displayed pronounced effects with the activity improving substantially as one alters both the nature of the reacting carbonyl group (urea > carbamate > amide) and the pyrazole C4 substituent (CN > H > Me). It was further demonstrated that the acyl chain of the N-acyl pyrazole ureas can be used to tailor the potency and selectivity of the inhibitor class to a targeted serine hydrolase. Thus, elaboration of the acyl chain of pyrazole-based ureas provided remarkably potent, irreversible inhibitors of fatty acid amide hydrolase (FAAH, apparent K = 100-200 pM), dual inhibitors of FAAH and monoacylglycerol hydrolase (MGLL), or selective inhibitors of MGLL (IC = 10-20 nM) while simultaneously minimizing off-target activity (e.g., ABHD6 and KIAA1363).
Topics: Amidohydrolases; Animals; Drug Design; Enzyme Inhibitors; Monoacylglycerol Lipases; Pyrazoles; Rats; Recombinant Proteins; Structure-Activity Relationship; Urea
PubMed: 30879861
DOI: 10.1016/j.bmc.2019.03.020