scholarly journals Synthesis and anаlgеsic activity 5-methyl-3-aryl[1,2,4]triazolo[4,3-a]pyrimidin-7-oles derivatives

2018 ◽  
pp. 55-61
Author(s):  
A. G. Ogorodnik ◽  
V. A. Yanchenko ◽  
L. S. Bobkova ◽  
N. M. Seredinska ◽  
A. M. Demchenko
Keyword(s):  
Analgesic Activity ◽  
1H Nmr Spectroscopy ◽  
The Body ◽  
Aryl Substituent ◽  
Hot Plate ◽  
Methyl Group ◽  
Structure Activity ◽  
Subsequent Cyclization ◽  
Fourth Position

Pain is a signal of inflammation and disruption of the body. It is the most important protective and adaptive mechanism that ensuring the safety of the individual. A strong and prolonged effect of "pain" irritant arising in injuries or after surgical manipulation transforms the protective reaction of the body to harmful factor that is the cause of secondary violations physiological processes. The aim of this work was the synthesis of substances in a series of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidine-7-ol and study the analgesic effect of the synthesized compounds. The objects of our research were selected derivatives of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidine-7-ol, which were synthesized by condensation and subsequent cyclization of 6-methyl-2-metylsulfanilpirymidyn-4-ol (1) with the corresponding substituted benzoic acid hydrazide The primary evaluation of analgesic activity conducted on thermal  stimulation models («hot plate»). A number of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol derivatives were synthesized, and their structure and purity were confirmed by 1H NMR spectroscopy. The analgesic activity of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol was investigated in order to reveal the structure-activity relationship. The screening for analgesic activity for 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol derivatives in in vivo experiments on hot plate models showed that the highest activity Was noted for the compound containing the methyl group in the fourth position of the aryl substituent, which is 184.28% of the change in the latent period of the reaction, which exceeds the action of the reference preparation of ketorolac by 71.57%. The introduction of halogens into the aryl moiety leads to a decrease in the analgesic activity of the compounds. A series of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidine-7-ol derivatives were synthesized by condensation and subsequent cyclization of 6-methyl-2-metylsulfanylpirymydyn-4-ol with relevant substituted hydrazide of benzoic acid. The structure and purity of obtained compounds were confirmed by 1H NMR spectroscopy. The analgesic activity of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol was investigated in order to reveal the structure-activity relationship. The screening of analgesic activity of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pirymidyn-7-ol derivatives in vivo models for «hot plate» shows that the highest activity was noted for compound containing methyl group in the fourth position of the aryl substituent, which is 184.28% change latent period reaction, that exceeds effect reference drug ketorolac at 71.57%. The introduction of halogens in the aryl fragment leads to a decrease analgesic activity of compounds.

Synthesis of 8-alkoxy-1,3-dimethyl-2, 6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides as analgesic and anti-inflammatory agents

2015 ◽  
Vol 21 (5) ◽  
pp. 273-278 ◽  
Author(s):  
Grażyna Chłoń-Rzepa ◽  
Agnieszka W. Jankowska ◽  
Małgorzata Zygmunt ◽  
Krzysztof Pociecha ◽  
Elżbieta Wyska
Keyword(s):  
Analgesic Activity ◽  
Structural Element ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Peripheral Mechanism ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Inhibit Tumor Necrosis Factor

AbstractA series of new 8-alkoxy-1,3-dimethyl-2,6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides 6–12 was synthesized and evaluated for the analgesic activity in two in vivo models: the writhing syndrome and the hot-plate tests. Among the investigated derivatives, compounds with N′-arylidenehydrazide moiety 9–12 show analgesic activity significantly higher than that of acetylsalicylic acid, which may indicate the importance of this structural element for analgesic properties. The lack of the activity in the hot-plate test may suggest that the analgesic activity of the newly synthesized compounds is mediated by a peripheral mechanism. The selected compounds 7 and 12 inhibit tumor necrosis factor α production in a rat model of lipopolysaccharide-induced endotoxemia, similarly to theophylline, which may confirm their anti-inflammatory properties.

scholarly journals Enrichment of Eucalyptus oil nanoemulsion by micellar nanotechnology: transdermal analgesic activity using hot plate test in rats’ assay

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zarith Asyikin Abdul Aziz ◽  
Hasmida Mohd Nasir ◽  
Akil Ahmad ◽  
Siti Hamidah Mohd Setapar ◽  
Hafandi Ahmad ◽  
...  
Keyword(s):  
Particle Size ◽  
Analgesic Activity ◽  
Eucalyptus Globulus ◽  
Ph Value ◽  
Activity Assay ◽  
Hot Plate ◽  
Spontaneous Emulsification ◽  
Grape Seed Oil ◽  
Tween 40

Abstract Eucalyptus globulus is an aromatic medicinal plant which known for its 1,8-cineole main pharmacological constituent exhibits as natural analgesic agent. Eucalyptus globulus-loaded micellar nanoparticle was developed via spontaneous emulsification technique and further evaluation for its analgesic efficacy study, in vivo analgesic activity assay in rats. The nanoemulsion system containing Eucalyptus-micelles was optimized at different surfactant types (Tween 40, 60 and 80) and concentrations (3.0, 6.0, 9.0, 12.0, 15.0, and 18.0 wt. %). These formulations were characterized by thermodynamically stability, viscosity, micelles particle size, pH, and morphology structure. The spontaneous emulsification technique offered a greener micelles formation in nanoemulsion system by slowly titrated of organic phase, containing Eucalyptus globulus (active compound), grape seed oil (carrier oil) and hydrophilic surfactant into aqueous phase, and continuously stirred for 30 min to form a homogeneity solution. The characterizations evaluation revealed an optimized formulation with Tween 40 surfactant type at 9.0 wt. % of surfactant concentration promoted the most thermodynamic stability, smaller micelles particle size (d = 17.13 ± 0.035 nm) formed with spherical shape morphological structure, and suitable in viscosity (≈2.3 cP) and pH value (6.57) for transdermal purpose. The in vivo analgesic activity assay of optimized emulsion showed that the transdermal administration of micellar nanoparticle of Eucalyptus globulus on fore and hind limb of rats, possessed the central and peripheral analgesic effects by prolonged the rats pain responses towards the heat stimulus after being put on top of hot plate (55 °C), with longest time responses, 40.75 s at 60 min after treatment administration. Thus, this study demonstrated that micellar nanoparticle of Eucalyptus globulus formed in nanoemulsion system could be promising as an efficient transdermal nanocarrier for the analgesic therapy alternative.

scholarly journals In vivo and in silico evaluation of analgesic activity of Lippia alba

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Md. Abdullah Aziz ◽  
Manna Mehedi ◽  
Mst. Irin Akter ◽  
Sadiur Rahman Sajon ◽  
Kishor Mazumder ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Analgesic Activity ◽  
In Silico ◽  
Cyclooxygenase 2 ◽  
Latency Time ◽  
Hot Plate ◽  
Standard Drug ◽  
Lippia Alba ◽  
Tail Immersion

Abstract Background This study was conducted to evaluate the analgesic activity of different extracts of Lippia alba (L. alba) along with in silico evaluation of analgesic activity of the isolated compounds from L. alba against cyclooxygenase-2 enzyme and ADME/T analysis of isolated compounds. Method In vivo analgesic activity of different extracts of L. alba was evaluated by acetic acid-induced writhing, tail immersion and hot plate on Swiss albino mice of either sex. In silico activity of the isolated compounds and ADME/T analysis were performed by Schrödinger-Maestro (Version 10.1) and OSIRIS Data warrior (version 4.6.1) softwares. Results Three different extracts (Methanolic extract: ME; Petroleum ether extract: PEE; Dichloromethane extract: DCME) of 250 mg/kg and 500 mg/kg doses were used in the experiments to evaluate analgesic activity. In acetic acid-induced writhing test, significant results were seen for PEE (500 mg/kg) and DCME (500 mg/kg), which were 53.09 ± 2.87 & 50.09 ± 4.24%, respectively. In tail immersion test, the best latency time was found at + 60 min for PEE (500 mg/kg) which is (5.65 ± 0.25) sec. For hot plate test, DCME at a dose 500 mg/kg showed the highest increase in latency time, which was 13.48 ± 0.33 s. In the case of in silico evaluation of analgesic activity, the compounds such as geranial, neral, (E)-caryophyllene, caryophyllene oxide, mussaenide, and 8-epi-loganin meet the condition of Lipinski’s rule of five. Among these safe compounds, 8-epi-loganin showed the best docking score of − 8.17 kcal/mol against cyclooxygenase-2 enzyme (PDB ID: 6COX), which was almost similar to that of the standard drug, Celecoxib (− 11.11 kcal/mol). Conclusion In conclusion, L. alba can be a potent source of analgesic medicine and further modification and simulation studies are required to establish the effectiveness of 8-epi-loganin.

scholarly journals In vivo Analgesic activity of methanolic extract of Helianthus annuus seeds

2016 ◽  
Vol 5 (4) ◽  
pp. 38-40 ◽  
Author(s):  
Rubab Tarannum Islam ◽  
Ahmed Tanjimul Islam ◽  
Mir Monir Hossain ◽  
Kishor Mazumder
Keyword(s):  
Body Weight ◽  
Acetic Acid ◽  
Helianthus Annuus ◽  
Analgesic Activity ◽  
Latency Period ◽  
Pharmaceutical Journal ◽  
Mice Model ◽  
Hot Plate ◽  
Writhing Test

The sunflower seed is the seed of the sunflower (Helianthus annuus). The methanol extract of seeds of Helianthus annuus were screened for analgesic activity in mice model to systematically explore the medicinal values of the plant. Acetic acid induced writhing and hot plate methods were used to confirm the central and peripheral analgesic action. In case of acetic acid-induced writhing test the extract showed significant (P <0.05) analgesic potential at doses 100 and 200 mg/kg body weight (50.35 and 57.85% inhibition, respectively). In the hot plate method, increase (p < 0.05) of latency period was also observed in comparison to standard aspirin. At 60 minutes, the latency period of two different doses (100 and 200 mg/kg body weight) was found at 13 ± 0.91 and 16.5 ± 1.55 second. The results obtained support the use of Helianthus annuus seeds in painful conditions acting both centrally and peripherally.Islam et al., International Current Pharmaceutical Journal, March 2016, 5(4): 38-40http://www.icpjonline.com/documents/Vol5Issue4/02.pdf

scholarly journals Synthesis and Analgesic Activity of η6-(Anisole)- Triscarbonyl-Chromium(0)

1999 ◽  
Vol 6 (1) ◽  
pp. 25-29
Author(s):  
Márcio Luís Andrade e Silva ◽  
Alberto Federman Neto ◽  
Joseph Miller
Keyword(s):  
Analgesic Activity ◽  
Wistar Rats ◽  
Pain Threshold ◽  
The Body ◽  
Test Method ◽  
Control Group ◽  
Synthetic Method ◽  
Hot Plate ◽  
Hot Plate Test ◽  
General Method

The general method for synthesis the η6-(arene)-triscarbonyl-chromium(0) complexes was modified and applied for preparation of η6-(anisole)-triscarbonyl-chromium(0) and the study of its analgesic activity was undertaken. A significant analgesic activity was observed after intraperitoneal injection, in Wistar rats. Two doses (30 and 50 mg/Kg of the body weight) of η6-(anisole)- triscarbonyl-chromium(0) were injected and the analgesic activity was evaluated by the Hot Plate Test method. They showed a significant analgesic effect in comparison with the control group and the group treated with dipyrone standard, but not so high when compared with the group treated with morphine standard. Overall, it was observed that the η6-(anisole)- triscarbonyl-chromium(0) was easily obtained by the modified synthetic method and was effective in increasing the pain threshold.

scholarly journals Assessment on antinociceptive actions of soluble fractions derived from edible mollusc (Bellamya bengalensis Lam.)

2017 ◽  
Vol 6 (12) ◽  
pp. 2916
Author(s):  
Anjan Adhikari ◽  
Sangita Bhattacharya ◽  
Abhijit Chanda ◽  
Tapas Kumar Sur
Keyword(s):  
Ethyl Acetate ◽  
Analgesic Activity ◽  
Phosphate Buffer ◽  
Ethyl Acetate Fraction ◽  
The Body ◽  
Analgesic Action ◽  
Hot Plate ◽  
Phosphate Buffer Saline ◽  
Tail Immersion ◽  
Bellamya Bengalensis

Background: Bellamya bengalensis, an edible bivalve mollusc is traditionally used in the treatment of joint pain, bone fracture, jaundice and eye infections. Present study was designed to find out the most potent analgesic fractions derived from the body mass of Bellamya bengalensis.Methods: The test specimen was collected, identified and fractionated with solvent medium like, phosphate buffer saline (PB), ethyl acetate (EB), methanol (MB) and chloroform (CB). Protein concentration of each fraction was determined. The antinociceptive activities were measured either by thermal models like, hot plate and tail immersion (central analgesic action) or by chemical model like acetic acid induced writhing (peripheral analgesic action) in mice. Diclofenac sodium was used as analgesic standard.Results: Significant peripheral and central analgesic activity showed by phosphate buffer saline fraction at 100mg/kg, even better than diclofenac standard at 10mg/kg. In hot plate and tail immersion tests, phosphate buffer saline showed the highest activity followed by methanol, chloroform and ethyl acetate fraction respectively. However, in case of peripheral analgesic experiment, phosphate buffer fraction exhibited maximum writhing inhibitory properties and that was followed by chloroform, methanol and ethyl acetate fraction respectively.Conclusions: Phosphate buffer saline fraction of Bellamya bengalensis showed maximum potential central and peripheral analgesic activity than any other fractions.

scholarly journals Synthesis And Anagesic activities of Quinazolin-4(3H)-One, 2-Methyl-4(3H)-Quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one

2020 ◽  
Vol 10 (4-s) ◽  
pp. 87-91
Author(s):  
P.O. Osarumwense ◽  
M.O. Edema ◽  
C.O. Usifoh
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Analgesic Activity ◽  
Cyclic Compound ◽  
Test Sample ◽  
Control Test ◽  
Methyl Group ◽  
Analgesic Activities ◽  
Quinazolinone Derivatives ◽  
Activity Method

Background: Objective: The current study is aimed at the synthesis of these quinazolinone derivatives quinazolin-4(3H)-One, 2-Methyl-4(3H)-quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one and evaluate them for their analgesic activity. Method: The condensation of 2-amino-methyl-4-methoxybenzoate with acetic anhydride yielded the cyclic compound 2-methyl-4, 5-disubstituted-1, 3-benzo-oxazine-4-one which further produce a novel 2,3-disubstituted quinazolin-4 ones via the reaction with hydrazine hydrate The quinazolinone derivatives quinazolin-4(3H)-One,  2-Methyl-4(3H)-quinazolinone  and 2–Phenyl-4(3H)-quinazolin-4(3H)–one were evaluated pharmacologically for their in vivo analgesic activities by acetic acid induced writhing in mice. The compounds synthesized were unequivocally confirmed by means of Infrared, Nuclear Magnetic Resonance (1H and 13C), Gas Chromatography Mass Spectrophotometer and Elemental analysis.The synthesized compounds were screened for their analgesic activity.Compounds 1,2 and 3 showed significant analgesic activity. Discussion: Compound 1 was characterized by the absence of methyl group and the presence of methyl group for compound 2. The test investigated compounds exhibited significant analgesic activity when compared with the control test sample. The compounds  synthesized  exhibited promising analgesic  activities against .  Conclusion: The compounds have high analgesic activity. Compound 3 has a higher activity  compared to Compound 2 and compound 2 has a higher analgesic activity compared to compound  1.  Compound 3 has a higher analgesic activity compared to the standard drugs Aspirin and Indomethacin. Keywords:  quinazolin-4(3H)-One, 2-Methyl-4(3H)-quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one quinazolin-4(3H)-one, analgesic activity.

Synthesis and Analgesic Activity of Monoterpenoid Aldehyde-derived Hydro-2H-chromeneols

2019 ◽  
Vol 17 (1) ◽  
pp. 68-78 ◽  
Author(s):  
Irina Il'ina ◽  
Ekaterina Morozova ◽  
Dina Korсhagina ◽  
Konstantin Volсho ◽  
Tat'yana Tolstikova ◽  
...  
Keyword(s):  
Analgesic Activity ◽  
Topical Issue ◽  
Hot Plate ◽  
One Pot ◽  
Hot Plate Test ◽  
Writhing Test ◽  
Structural Types ◽  
In Vivo Tests ◽  
Low Toxicity

Background: Despite a variety of drugs used to stop acute pain, problems related to their insufficient efficacy and undesirable side effects have remained unresolved. Therefore, the search for analgesics of new structural types, which combine high activity with low toxicity, is a topical issue. It is known that a number of compounds with a hydrogenated 2H-chromene skeleton exhibit significant analgesic activity in in vivo tests. Methods: New hydro-2H-chromenols containing monoterpenoid moieties were obtained via one-pot synthesis by the interaction between para-menthane alcohols and commercially available monoterpene aldehydes: Citral, hydroxycitronellal, myrtenal, and perillaldehyde. The analgesic activity of these compounds wаs studied in the acetic acid-induced writhing test and hot plate test. Results: The target compounds were characterized using NMR and HR-MS. Most of them exhibited pronounced analgesic activity. Conclusion: Due to high analgesic activity, (2S,4aR,8R,8aR)-2-((E)-2,6-dimethylhepta-1,5-dien-1- yl)-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diol is considered as candidate compound to participate in further research.

scholarly journals The analgesic activity of new sulfur-containing di- and tetrahydropyridine derivatives in the hot plate test

2021 ◽  
pp. 45-55
Author(s):  
E.Yu. Bibik ◽  
◽  
L.I. Kurbanov ◽  
S.A. Grygoryan ◽  
D.S. Krivokolysko ◽  
...  
Keyword(s):  
Analgesic Activity ◽  
High Efficiency ◽  
Pain Syndrome ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Reference Drug ◽  
Plate Test ◽  
Metamizole Sodium ◽  
Sulfur Containing

Nowadays the search of new high-efficiency and safe drugs for the pharmacotherapy of diseases accompanied by pain syndrome is an active area of modern pharmacological research. 170 new derivatives of di- and tetrahydropyridines synthesized on the basis of the Chemex Research Laboratory, Vladimir Dahl Lugansk State University were exposed to the virtual bioscreening using the Swiss Target Prediction software. The paper describes screening studies in vivo of 5 samples of sulfur-containing di- and tetrahydropyridines (laboratory codes d02-138, as-262, f02-079, cv-074, cv-143) in the standard hot plate test in comparison with the reference drug — metamizole sodium. The compounds in the dose of 5 mg/kg were given intragastrically 1 hour and a half before placing the rats on the hot plate, the reference drug in the dose of 7 mg/kg also was given intragastrically 1 hour and a half before placing the rats on the hot plate. The compounds with laboratory codes as-262 (allyl 6-({2-[(4-acetylphenyl)amino]-2-oxoethyl}thio)-5-cyano-4-(2-furyl)-2-methyl-1,4-dihydropyridine-3-carboxylate) and d02-138 (ethyl 4-[({[3-cyano-5-{[(2,4-dichlorophenyl)amino]carbonyl}-4-(2-furyl)-6-methyl-1,4-dihydropyridinе-2-yl]thio}acetyl)amino]benzoate) possess the most pronounced analgesic activity in the dose of 5 mg/kg, they demonstrated 2.03 and 1.9-fold efficiency in comparison to metamizole sodium respectively. The rest three specimens demonstrated metamizole sodium-like analgesic activity.

scholarly journals A study to evaluate the analgesic activity of Origanum vulgare in mice using hot plate method

2019 ◽  
Vol 8 (7) ◽  
pp. 1563
Author(s):  
Siddhi Raveendran ◽  
A. V. Tilak ◽  
Shraddha Yadav ◽  
Sayan Das ◽  
Vishwadeep Madrewar ◽  
...  
Keyword(s):  
Reaction Time ◽  
Analgesic Activity ◽  
International Association ◽  
In Vivo Model ◽  
Control Group ◽  
P Value ◽  
Origanum Vulgare ◽  
Hot Plate ◽  
Plate Method

Background: The International Association for Study of pain, has defined pain as actual or potential tissue damage or described in terms of such damage. But the burden of unwanted side effects with current regimens are high. To explore the potential of Ayurveda drugs, this study is done by using Origanum vulgare.Methods: In vivo model used-Hot plate method. Origanum vulgare (84 mg/kg p.o) was administered in mice. The analgesic activity was studied by recording the reaction time after administration of the drug at frequent intervals up to 3 hrs. The results were analysed by ANOVA and Tukey’s test. P value <0.05 was considered as significant. Pentazocine showed statistically prolongation in the reaction time after 30 min as compared to Origanum vulgare.Results: In hot plate method, pentazocine showed statistically significant increase in the reaction time after 30 min of administration as compared to control group. However, Origanum vulgare in a dose of 84 mg/kg showed significantly increase in the reaction time after 30 min of administration as compared to control group. On comparing pentazocine and Origanum vulgare, pentazocine showed highly significant increase in the reaction time after 30 min as compared to Origanum vulgare at 84 mg/kg dose.Conclusions: From the present study, it was concluded that extract of Origanum vulgare exerted analgesic activity in both the models. However, it was less potent than pentazocine. Thus, Origanum vulgare can be used in mild to moderate painful conditions.

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