An-overview-on-the-biological-activities-of-pyrazole

The purpose of this study is to provide a summary of the various pyrazole moieties' pharmacological actions. Pyrazole is a well-known and essential nitrogen-containing 5-membered heterocyclic compound, and different techniques for synthesis have been developed. Pyrazole, also known chemically as 1, 2-diazole, has become a prominent subject due to its numerous applications. Numerous pyrazole derivatives have been discovered to have a wide range of biological functions, which has fueled study in this area. Pyrazoles and their variants are among the most powerful groups of chemicals, with anti-bacterial, anti-convulsant, analgesic, anti-microbial, anti-inflammatory, anti-diabetic, sedative, anti- rheumatic, anticancer, and anti-tubercular properties. The goal of this study was to compile literary work on pyrazole for its different pharmacological activities, as well as to report on new efforts made on this moiety.

Design, synthesis, antibacterial and antitumor activities of novel pyrazolo3,4-bpyridine-4-one-5-carboxylic acid derivatives / 药学学报

To discover new structural hits, based on the important role of pyrazole ring and fragment of pyridinone carboxylic acid in drug design, novel title pyrazolo[3,4-b]pyridine-4-one-5-carboxylic acid derivatives (10a-10p) were designed and synthesized, the structures were confirmed by spectral data and elemental analyses. The antibacterial and antitumor activities were evaluated by the measured minimum inhibitory concentration (MIC) values against the tested four strains and half inhibitory concentration (IC50) values against the tested four cancer cells, respectively. The results displayed markedly poor antibacterial activity and observably potent antitumor activity. In particularly, the title difluorophenyl (10d, 10e, 10f), pyridyl (10j), ethyl (10k) and cycloproyl (10l) compounds exhibited comparable activity against Capan-1 and A549 cells to that of the comparison doxorubicin. Thus, pyrazolo[3,4-b]pyridine-4-one-5-carboxylic acid derivatives as promising antitumor hits need to be developed.

Synthesis and evaluation of antifungal activity studies of novel 2-(2-pyridyl)-2H-pyrazole-3-carboxamide derivatives

Background: Invasive fungal infections have negative impact on the health of immunocompromised individuals. With the development of fungal resistance to currently available antifungal drugs, there is a need to develop novel compounds with antifungal activity. Aims and Objectives: The objectives of the study are as follows: (1) To synthesize novel 2-(2-pyridyl)-2H-pyrazole-3-carboxamide derivatives and (2) to evaluate the antifungal activity of novel 2-(2-pyridyl)-2H-pyrazole-3-carboxamide derivatives. Materials and Methods: Novel 2-(2-pyridyl)-2H-pyrazole-3-carboxamide derivatives were prepared by multi step synthesis and characterized by LC-MS, 1HNMR and 13C NMR. The antifungal activity of these derivatives was assessed using Fusarium oxysporum, Aspergillus flavus, and Candida albicans by disc diffusion method. Results: We have synthesized fourteen derivatives of 2-(2-pyridyl)-2H-pyrazole-3-carboxamide. Most of the compounds possess good antifungal activity against F. oxysporum and C. albicans strains. Conclusion: We synthesized a series of novel 2-(2-pyridyl)-2H-pyrazole-3-carboxamide derivatives having good antifungal activity against F. oxysporus and C. albicans using a simple and low cost procedure.

Antimicrobial evaluation and molecular properties prediction of pyrazolines incorporating benzofuran and pyrazole moieties

A series of chalcones 3–5, 1H-pyrazolines 6–8, N-phenylpyrazolines 9–11, and N-acetylpyrazolines 12–14incorporating benzofuran and pyrazole moieties were synthesized and screened for their in vitro antimicrobial activityagainst some of pathogenic microorganisms. Among the screened compounds, 7 and 13 showed the most promisingantibacterial activity against Escherichia coli (G-). Compound 11 displayed broad spectrum antibacterial activityagainst Bacillus subtilis (G+). Moreover, compounds 10 and 4 were found to be the most potent antifungal agentagainst Candida albicans and Aspergillus niger, respectively. Also, the molecular properties prediction and druglikeness model score (DLS) of all the synthesized compounds were calculated by SwissADME and MolSoft websites,respectively. The two compounds 7 and 13 were found to be maximum DLS of 0.75 and 0.83, respectively.

Intermediate-conductance Ca2+-activated K+channel:research advances / 国际药学研究杂志

Intermediate-conductance Ca2+-activated K+channel ,also known as KCa3.1,IKCa and SK4,is widely distributed in fibroblasts,proliferating smooth muscle cells,endothelial cells,T lymphocytes,plasma cells,macrophages,and epithelial cells, and involved in the pathological and physiological processes such as vascular contraction,inflammation ,calcification,tissue fibrosis, immune response,malignant tumor,internal and external secretory glands. In recent years,it has been found that blocking the KCa3.1 pathway or knockouting the gene can significantly prevent the pathophysiological process of its involvement. The recent use of the specific blocker TRAM-34 in animals and humans shows its safety and tolerability,providing a new direction for the treatment of related diseases. In this article,the research progress in KCa3.1 related diseases in recent years is reviewed.

Intermediate-conductance Ca2+-activated K+ channel: Research advances / 国际药学研究杂志

Intermediate-conductance Ca2+-activated K+ channel, also known as KCa3.1, IKCa and SK4, is widely distributed in fibroblasts, proliferating smooth muscle cells, endothelial cells, T lymphocytes, plasma cells, macrophages, and epithelial cells, and involved in the pathological and physiological processes such as vascular contraction, inflammation, calcification, tissue fibrosis, immune response, malignant tumor, internal and external secretory glands. In recent years, it has been found that blocking the KCa3.1 pathway or knockouting the gene can significantly prevent the pathophysiological process of its involvement. The recent use of the specific blocker TRAM-34 in animals and humans shows its safety and tolerability, providing a new direction for the treatment of related diseases. In this article, the research progress in KCa3.1 related diseases in recent years is reviewed.

Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

Synthesis and in vitro Anti Microbial Evaluation Including Anti-Malarial Activity of Pyrazole Based Novel Cinnoline Derivatives.

A Series of 4-methyl-3-[5-(substituted phenyl)-4, 5-dihydro-1H-Pyrazol-3-yl] Cinnoline-6-Sulfonamide were synthesized from 4-methyl-3-acetylcinnoline-6-Sulfonamido chalcones and hydrazines. The structure of the synthesized compounds were characterized by UV, IR, NMR & Mass spectral data, and evaluated for their in vitro anti-malarial and anti-bacterial activity to get new congeners as analogs of Pyrazole based Cinnoline compounds as a potent anti-Malarial and anti-microbial agents. All analogues exhibited in vitro anti-malarial activity against Plasmodium falciparum and all the analogues showed good anti-bacterial activity against various pathogenic microbes.

Tricyclic Pyrazoles: Synthesis, Characterization, Antimicrobial, Antituberculosis, and Antitumor Activity of N,1-Diphenyl-1,4-dihydrothiochromeno[ 4,3-c]pyrazole-3-carboxamide-5,5-dioxide Derivatives.

Aims: A series of N,1-diphenyl-1,4-dihydrothiochromeno[4,3-c]pyrazole-3-carboxamide 5,5-dioxide derivatives (6a-m) were synthesized and evaluated for anticancer, antibacterial, and antifungal activity. Methodology: Reaction of 2,3-dihydro-4H-thiochromen-4-one 1,1-dioxide 2 with diethyl oxalate in ethanol in the presence of a base afforded the Claisen condensation product 3. Subsequent reaction of 3 with phenylhydrazine hydrochloride at reflux in ethanol afforded ethyl 1-phenyl-1,4-dihydrothiochromeno[4,3-c]pyrazole-3-carboxylate 5,5-dioxide (4). Alkaline hydrolysis of 4 furnished the corresponding 1-phenyl-1,4- dihydrothiochromeno[4,3-c]pyrazole-3-carboxylic acid 5,5-dioxide 5. The pyrazole acid 5 was converted into the corresponding acid chloride followed by treatment with an excess of the appropriate amine to give 6a-m. Results: Compound 6k showed better activity than chloroamphenicol against Klebsiella pneumoniae and Escherichia coli and equipotent to clotrimazole in inhibiting the growth of Candida albicans (MIC 3.125 μg/mL). All compounds were screened for their cytotoxic activity against two tumor cell lines, namely, human colon tumor cell line (HCT116) and human cervical cancer cell line (HeLa) using the colorimetric MTT assay. Most of the tested compounds exhibited potent antitumor activity. Particularly, compound 6k displayed the highest activity among the tested compounds with IC50 equal to 17 μM (HeLa) and 15 μM (HCT116) respectively. Among the tested compounds, 6k was found to be more active against M. tuberculosis, (H37Rv) with minimum inhibitory concentration (7.8 μM). Conclusion: The chloro- (6b and 6c), 2-aminobenzothiazole- (6l), and 4-aminoantipyrine- (6k) linkages exhibited better antimicrobial activity than their counterparts. Compound 6k was found to possess comparatively more antimicrobial, antituberculosis, and antitumor activity against the other derivatives.

Synthesis and antibacterial activity of some 3-(5-aryl-4H-pyrazol-3-yl).

A series of 3-(5-aryl-4H-pyrazol-3-yl)anthracen-10(9H)-ones were synthesized from anthracen-10(9H)-one (1) and studied for their in vitro antibacterial activity. Anthracen- 10(9H)-one after Friedel crafts acetylation with acetyl chloride yielded 3-acetylanthracen- 10(9H)-one (2) which on further reaction with substituted aromatic aldehydes in the presence of catalytic amount of sodium hydroxide in water and ethanol furnished the corresponding 3-(3-arylacryloyl)anthracen-10(9H)-ones (3a-g) as intermediate compounds, which on further reaction with hydrazine hydrate in absolute ethanol formed the title compounds 3-(5-aryl-4H-pyrazol-3-yl)anthracen-10(9H)-ones (4a-g). These compounds were characterized by elemental analysis, IR, Mass and 1H-NMR spectral data. All the compounds were evaluated for their in vitro antibacterial activity against two gram positive strains (Bacillus subtilis and Staphylococcus aureus) and two gram negative strains (Escherichia coli and Pseudomonas aeruginosa) taking ciprofloxacin as a standard drug. Some of the compounds showed significant antibacterial activity.

DNA binding and cytotoxicity of newly synthesized schiff base (z)-4-(((2-hydroxy phenyl) amino) (phenyl) methylene)-3-methyl-1-phenyl-1hpyrazol-5(4H)-one and its analogues.

A novel Schiff base (Z)-4-(((2-hydroxy phenyl)amino)(phenyl)methylene)-3-methyl-1-phenyl-1Hpyrazol- 5(4H)-one and its analogues were synthesized by condensation of 5-methyl-2-phenyl-4-substituted pyrazolin- 3-one with 2-amino phenol from alcoholic solution.Schiff base ligands arecharacterizedby IR, UV, NMR, elemental analysis and single crystal X- ray diffraction analysis. These potential ligands are subjected to DNA binding analysis against the Calf thymus DNA, their binding constant values were calculated and compared to the standard ruthenium intercalators. The cytotoxic natureof these Schiff base ligands was also studied with the human breast cancer cell line MCF-7 and their IC50 values were determined.

Synthesis of novel Naphthalene COX inhibitors for anti-inflammatory activity.

Inflammation forms the part of various diseased conditions. To treat inflammation variety of anti inflammatory agents are synthesized, they showed undesirable side effects. In order to avoid these side effects, nonsteroidal anti-inflammatory drugs were developed. Research is a continuous and never ending process; efforts are being made to improve the present drug profile such that present side effects can be eliminated. Syntheses of number of naphthalene derivatives with pyrazole moiety were completed. The present classification records for numerous naphthalene derivatives (naproxen and nabumetone) and also many anti-inflammatory drugs containing diaryl heterocycle(celecoxib,rofecoxib) are available as reference, therefore some new non-vicinal 3,5 diaryl heterocycles,in which naphthalene as one of aryl ring and pyrazole as central scaffold was prepared and evaluated for anti-inflammatory activity. The purity of all compounds has been examined by the TLC and structure is confirmed by different analytical techniques like IR, Mass spectroscopy and NMR. Further, the synthesized drugs were evaluated for in vivo anti inflammatory activity by carrageenan induced rat paw edema test using Indomethacin as a standard drug. In conclusion, we have found that two compounds showed equipotent activity while other two showed slightly more anti-inflammatory activity respectively.

Antibacterial, Molecular Docking, DNA Binding and Photocleavage Studies on Novel Heterocyclic Pyrazoles.

The antibacterial activity, in-silico DNA molecular docking, DNA binding and photo cleavage studies of newly synthesized pyrazole is described. Antibacterial potential of these compounds screened against a wide range of Gram-positive and Gram-negative bacteria showed significant zone of inhibition and MIC with standard drug ciproflaxin is investigated. Among all the orientation of binding, fourth orientation showed significant binding and revealed that the binding and docking energy of 4a was -8.62 and -8.66 and inhibition constant 7.46 X e-6. The absorption spectra showed the dynamic interaction with CT DNA and as proficient DNA intercalator (Kb = 4.5×104 M-1). The viscosity measurements and thermal denaturation affords the positive results towards DNA intercalation in both the studies. The light induced DNA damage was pragmatic in the absence of various ‘‘inhibitors’’ shows in photo cleavage activities at 360 nm.

Reaction of phenylhydrazo ethylacetoacetate with cyano acetyl hydrazine: Novel synthesis of pyridazine and pyrazole derivatives and their anti-tumor evaluations.

The reaction of phenylhydrazoethyl acetoacetate (1) with cyanoacetyl hydrazine (2) in an oil bath in the presence of ammonium acetate gave the pyridazine derivative 4. However, carrying the same reaction but in ethanolic/Et3N gave the pyrazole derivative 5. Compounds 4 and 5 were used in a series of heterocyclization reactions to afford products that showed anti-tumor activities towards three cell lines namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF- 268).

Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker’s yeast-induced fever. TFDPs or vehicle (5 percent Tween 80 in 0.9 percent NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker’s yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 μmol/kg, respectively, 4 h after yeast injection) attenuated baker’s yeast-induced fever by 61 and 82 percent, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker’s yeast-induced increases of IL-1β or TNF-α levels, 3-ethyl-TFDP caused a 42 percent reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.