Analgesic Activity Research Articles

Ameliorative effects of Atriplex crassifolia (C.A.Mey) on pain and inflammation through modulation of inflammatory biomarkers and GC-MS-based metabolite profiling.

Atriplex crassifolia (A. crassifolia) is a locally occurring member of Chenopodiaceae family that has been used in folk medicine for the treatment of joint pain and inflammation. The present study was focused to determine the analgesic and anti-inflammatory potential of the plant. n-hexane (ACNH) and methanol (ACM) extracts of A. crassifolia were evaluated for in vitro anti-inflammatory potential using protein denaturation inhibition assay. In vivo anti-inflammatory potential was determined by oral administration of 250, 500, and 1000mg/kg/day of extracts against carrageenan and formalin-induced paw edema models. Inflammatory mediators such as TNF-α, IL-10, IL-1β, NF-kB, IL-4, and IL-6 were estimated in blood samples of animals subjected to formalin model of inflammation. Analgesic activity was determined using acetic acid-induced writhing and tail flick assay model. Phytochemical profiling was done by GC-mass spectrophotometer. The results of in vitro anti-inflammatory activity revealed that both ACNH and ACM displayed eminent inhibition of protein denaturation in concentration-dependent manner. In acute in vivo carrageenan-induced paw edema model, both extracts reduced inflammation at 5th and 6th hour of study (p < 0.05). A. crassifolia extracts exhibited significant inhibition against formalin-induced inflammation with maximum effect at 1000mg/kg. ACNH and ACM significantly augmented the inflammatory mediators (p < 0.05). Levels of TNF-α, IL-6, IL-1β, and NF-kB were reduced, while those of IL-4 and IL-10 were upregulated. ACNH displayed maximum analgesic effect at 1000mg/kg, while ACM showed potent activity at 500 and 1000mg/kg. The extracts restored the CBC, TLC and CRP toward normal. GC-MS analysis revealed the presence of compounds like n-hexadecanoic acid, Phytol, (9E,11E)-octadecadienoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, 1-hexacosene, vitamin E, campesterol, stigmasterol, gamma sitosterol in both extracts. These compounds have been reported to suppress inflammation by inhibiting inflammatory cytokines. The current study concludes that A. crassifolia possesses significant anti-nociceptive and anti-inflammatory potential owing to the presence of phytochemicals.

A Pharmacognostic, phytochemical and pharmacological review of Pterocarpus marsupium: Comprehensive Review

Research in herbal drug is need of the hour to find definite lead for discovery of medicine from plant source. Many traditional medicinal plants are under screening to scientifically reinforce their traditional claims. Pterocarpus marsupium is time tested important source of herbal medicine which has been used extensively for treatment of diabetes mellitus. It has also exhibited antimicrobial activity, analgesic activity, anticataract activity. Acute toxicity test determines safe dose of the Pterocarpus marsupium. Various extraction methods such as Infusion, Decoction, Maceration, Percolation and Hot Water Extraction s employed for efficient extraction of phytoconstituents. Primary phytoconstituents present in the bark comprises of liquiritigenin, isoliquiritigenin, pterosupin, epicatechin, and pterostilbene. Current review is carried out to study pharmacognstic, phytochemical and pharmacological activity of the drug, which can be useful for researcher to provide synoptic overview about Pterocarpus marsupium &#x0D; Keywords: Pterocarpus marsupium, Review, Fabaceae, Indian kino, Asan

Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative

Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative. Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD50 for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically. Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity. Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.

Investigation of anti-nociceptive, anti-inflammatory potential and ADMET studies of pure compounds isolated from Isodon rugosus Wall. ex Benth.

The strong ethnopharmacological utilization of Isodon rugosus Wall. Ex. Benth is evident in the treatment of several types of pain and inflammation, including toothache, earache, abdominal pain, gastric pain, and generalized body pain and inflammation. Based on this background, the antinociceptive effects of the crude extract, various fractions, and essential oil have been reported previously. In this research work, we isolate and characterize pure bioactive compounds from I. rugosus and evaluate possible mechanisms using various in vivo and in vitro models. The pure compounds were analyzed for analgesic and anti-inflammatory activities through various assays. The column chromatography of the chloroform fraction of I. rugosus led to the identification of two pure compounds, i.e., 1 and 2. Compound 1 demonstrated notable inhibition (62% writhing inhibition, 72.77% COX-2 inhibition, and 76.97% 5-LOX inhibition) and anti-inflammatory potential (>50% paw edema inhibition at various intervals). The possible mechanism involved in antinociception was considered primarily, a concept that has already been elucidated through the application of naloxone (an antagonist of opioid receptors). The involvement of adrenergic receptors was investigated using a hot plate model (an adrenergic receptor antagonist). The strong ethnomedicinal analgesic background of I. rugosus, supported by previous reports and current observations, leads to the conclusion that I. rugosus is a potential source of antinociceptive and anti-inflammatory bioactive compounds. It may be concluded from the results that the isolated analgesic compounds of I. rugosus may be a possible alternative remedy for pain and inflammation management with admirable efficacy and safety profiles.

Isolation, invitro, invivo anti-inflammatory, analgesic and antioxidant potential of Habenaria plantegania Lindl.

Habenaira plantaginea belong to orchid family which is native to Asia. Members of this family are commonly famous for the cure of pain and inflammation. To date, no research was found on isolation of compounds from this plant for the treatment of inflammation and analgesia nor has been published to our knowledge. The purpose of this study was to evaluate an analgesic, anti-inflammatory and anti-oxidant activity of the isolated compound from the most potent chloroform sub-fraction and the isolated compounds form the habenaria plantaginea. Anti-inflammatory analgesic and antioxidant potential of the various chloroform sub-fractions and isolated compounds from the most potent sub-fraction (HP-1 & HP-1) were screened for their in vitro enzymatic assays. Furthermore, prior to in-vivo investigation, the isolated compounds were subjected for their toxicity study. The potent compound was then examined for acetic acid-induced writhing, hot plate test, carrageenan-induced inflammation assays. Further various phlogistic agents were used for the evaluation of mechanism. In the COX-2 inhibitory assay the chloroform sub fraction Cf-4 demonstrated excellent activity as compared to the other sub-fraction with 92.15% inhibition. The COX-2 enzyme make prostaglandins which are directly involved in inflammation. Likewise against 5-LOX the Cf-4 was the most potent sub-fraction with IC50 3.77µg/mL. The 5-LOX catalyzes the biosynthesis of leukotrienes which is a group of lipid mediators of inflammation derived from arachidonic acid. Free radicals can induce inflammation through cellular damage while chronic inflammation generates a large number of free radicals, whose eventually lead toinflammation. In antioxidant assays the Cf-4 fraction was displayed excellent results against ABTS, DPPH and H2O2 free radical with 88.88, 77.44, and 65.52% inhibition at highest concentration. Likewise, the compound HP-1 demonstrated 88.81, 89.34 and 80.43% inhibition while compound HP-2 displayed 84.34, 91.52 and 82.34% inhibition against ABTS, DPPH and H2O2 free radical which were comparable to the standard drug ascorbic acid respectively. This study's findings validate the use of this species as traditional use.

Investigation of the Effects of 1,2,4‐Triazole and Thiazole Ring‐Containing Hybrid Molecules on Carbonic Anhydrase I and II

AbstractCarbonic anhydrase (CA, EC 4.2.1.1) is an enzyme that catalyzes the reversible reaction of carbon dioxide to bicarbonate and a proton under physiological conditions. Pharmaceutical research has gained importance since the design of novel compounds that inhibit CA I–II isoenzymes has a promising approach for pharmacological intervention in many diseases. Triazole derivatives have attracted attention due to their chemotherapeutic, antifungal, antiviral, antibiotic, analgesic, and antifungal activities. Therefore, in this study, the effect of 1,2,4‐triazole and thiazole ring‐containing compounds on human carbonic anhydrase I (hCA I) and II (hCA II) isoenzymes were investigated in vitro. For this purpose, hCA I and hCA II isoenzymes were purified by Sepharose‐4B affinity column chromatography. Estimation of inhibition mechanism and drug‐likeness characteristics of compounds were also determined using molecular docking simulation. The inhibitory effects of ten compounds were investigated. Activity vs. concentration graphs were prepared for each compound and IC50 values or AC50 were calculated from these graphs. It was revealed that some of the compounds exhibited selective inhibition on carbonic anhydrase isoenzymes. The studied compounds are considered to be drug candidates.

Anti-parkinsonian, anti-inflammatory, anti-microbial, analgesic, anti-hyperglycemic and anticancer activities of poly-fused ring pyrimidine derivatives

Purpose: To investigate the anti-inflammatory, anti-cancer, anti-parkinsonian, anti-microbial, analgesic, and anti-hyperglycemic properties of a variety of poly-fused pyrimidine derivatives.&#x0D; Methods: A novel series of fused pyrimidine derivatives 1-6 were synthesized by reacting amino pyrazole derivatives with active methylene derivatives to give the corresponding compounds 1-6. Anti-parkinsonian activity was investigated with benzotropene as a reference drug, anti-inflammatory effect in mice was evaluated using carrageenan in paw edema with indomethacin as reference drug, anti-microbial activity was assessed using nutritional agar with ciprofloxacin and ketoconazole as reference drugs, analgesic activity was evaluated using valdecoxib as reference drug, anti-hyperglycemic activity was investigated using alloxan and sucrose models (SLM) with pioglitazone as reference drug and anticancer activity was investigated using the MTT micro-cultured tetrazolium assay method with doxorubicin as reference drug.&#x0D; Results: Pyrimidine derivatives 1-6 possess significant active anti-parkinsonian, anti-inflammatory, anti-microbial, analgesic, anti-hyperglycemic and anticancer activities in comparison to the reference drugs used for each model. Compared to Benzotropene®, compounds 1 and 3 showed a significantly stronger anti-parkinsonian activity (p &lt; 0.03). Compound 3 showed a significantly stronger anti-inflammatory effect than Indomethacin® (p &lt; 0.05). Compounds 5 and 6 exhibited significant anti- microbial activity compared to ciprofloxacin® (p &lt; 0.05). Compounds 4 and 6 exhibited significantly improved analgesic activity as compared to Valdecoxib® (p &lt; 0.01). Compounds 1 and 3 exhibited significantly higher anti-hyperglycemic effects in SLM model when compared to pioglitazone® (p &lt; 0.02). Compound 5 demonstrated the highest activity against human colon cancer cell line (HT-29) and human prostate cancer cell line (DU145), and also, significantly improved level of efficacy against human lung cancer cell line (A549) compared to Doxorubicin® (p &lt; 0.02). &#x0D; Conclusion: Using the six pyrimidine derivatives 1 - 6 as a lead molecule, a novel class of clinically beneficial anti-cancer, anti-inflammatory, anti-microbial, analgesic, and anti-hyperglycemic drugs may be produced.

Synthesis and Anti-Inflammatory Activity of (Z)-4-(2-(3-Oxopiperazin-2-ylidene)acetyl)benzoic Acid

Non-steroidal anti-inflammatory drugs (NSAIDs) are an important class of medications; however, they have some drawbacks. We are developing a new NSAID with pronounced anti-inflammatory and analgesic activities and a very low toxicity—(Z)-3-(2-oxo-2-(p-tolyl)ethylidene)piperazin-2-one (piron). In this work, we describe the synthesis of the main metabolite of piron—(Z)-4-(2-(3-oxopiperazin-2-ylidene)acetyl)benzoic acid. The anti-inflammatory activity of the synthesized metabolite was determined in vivo.

NYCTANTHES ARBORTRITIS LINN: AN ETHNOPHARMACOLOGICAL MIRACULOUS NATURAL RESOURCE

Nyctanthes arbortritis (Parijat tree) is a medicinal plant that has long been utilized in a variety of Ayurvedic formulations to treat a range of ailments. Many medicinal qualities like analgesic, antipyretic, antifungal, antibacterial, and anti-cancer properties, have been identified through comprehensive research on the pharmacological screening of Nyctanthes arbortritis. It has been demonstrated that the plant both inhibits the growth of certain cancer cells and has cytotoxic effects on them. As a promising therapy option for a range of inflammatory and pain related disorders, the extracts of its different plant parts have also been discovered to possess strong anti-inflammatory and analgesic activity. The plant extracts also have strong antifungal and antibacterial properties, which makes them a possible medicinal source for the creation of novel antibiotics. In this article, we have represented the collective scientific information about the various phytoconstituents and pharmacological activities of the Nyctanthes arbortritis.

Relevance of the Development of Dental &lt;i&gt;In situ&lt;/i&gt; Implant for Post-resection Therapy (Review)

Introduction. The problem of pain relief after surgery is relevant in modern dentistry, as pain control is an important part of treatment. In addition to anesthesia, there are other problems of post-resection therapy such as bleeding from the wound and inflammation. Modern dental practice does not have a targeted delivery system or a medical product with analgesic, anti-inflammatory, anesthetic or hemostatic action, which ensures high adherence of patients to the ongoing post-resection therapy.Text. To solve this problem, it can be proposed to develop an in situ implant – a dosage form that is formed directly at the injection site, in the alveolar socket. Targeted delivery system has advantages: no need to use a medical dressing material; no risk of secondary contamination; dosing accuracy and target delivery to the lesion locus; high mucoadhesion to the site of application; the duration of the active ingredient release and others. The purpose of the review is to substantiate the possibility and relevance of developing a new in situ implant system for use in dental post-resection practice. The study was conducted on the main databases of publications (Scopus, Web of Science, PubMed and others), and patent search database on materials published from 2000 to the present. The study describes the currently existing in situ systems for dental problems, which could be a prototype of systems for delivering an anesthetic directly to the tooth socket, the polymers used to create them and the possibility of releasing drugs, and also characterizes existing drugs for the pain relief (applied both locally and for systemic action), in comparison with in situ systems, which have certain advantages and great potential for development.Conclusion. Based on the results of the work, a conclusion about the possibility of pharmaceutical development of dental in situ implants was made, and the most promising polymers for phase transition in the alveolar socket were identified.

Exploring the impact of seasonal variations on the chemical composition, antinociceptive, and anti-inflammatory properties of Pogostemon heyneanus Benth. essential oil.

Background: Pogostemon heyneanus leaves infusions are relevant in ethnopharmacology for treating colds, coughs, headaches, and asthma. Purpose: The essential oil chemical composition of a Pogostemon heyneanus specimen was monthly monitored from October 2021 to July 2022 to evaluate the climatic influences on its yield and chemical composition and antinociceptive, andanti-inflammatory properties. Methods: The leaves, collected monthly over a 10-month period, were submitted to hydrodistillation. The oils obtained were analyzed by gas chromatography coupled to a mass spectrometer and gas chromatography coupled to flame ionization detector. The P. heyneanus essential oil (PhEO) was tested in vivo to evaluate its peripheral analgesic actions through the abdominal writhing test induced by acetic acid, and peripheral analgesia by tail immersion. Neurogenic and inflammatory pain were evaluated by formalin test, and acute oral toxicity of the oil was also verified. Results: PhEO presented 27 chemical constituents with the highest predominance of patchoulol (43.6%-76.9%), α-bulnesene (0.2%-12.7%), α-guaiene (0.4%-8.9%), seychellene (3.8%-5.1%) and pogostol (0.0%-8.2%). The climatic parameters insolation, humidity, rainfall, and temperature did not influence the essential oil yield or the main chemical constituents, except for pogostol, which presented a strong (r = 0.73) and statistically significant (p < 0.05) correlation with temperature. PhEO did not display toxicity at the maximum 300mg/kg dosage. The oil showed low peripheral and central analgesic action at 100mg/kg, while in the neurogenic and inflammatory pain inhibition tests, no actions related to PhEO were observed. In the carrageenan-induced peritonitis test, PhEO did not reduce the migration of leukocytes to the peritoneal cavity compared to the control group. Conclusion: Pogostemon heyneanus is a resistant plant to seasonal influences and a source of patchoulol. Despite ethnopharmacological indications, no in-vivo biological activities such as neurogenic or inflammatory pain were identified in the present work. So, the low influence of the climatic parameters on chemical composition can infer that the low pharmacological activity is also not subject to climatic variations, that is, it does not change due to the climate.

A Review on the Recent Multicomponent Synthesis of 4H-Pyran Derivatives

Abstract: 4H-Pyran is a well-known moiety, which appears in various natural and synthetic products. These compounds include various biological activities like anti-hepatotoxic, antitumor, anti-inflammatory, antioxidant, anti-spasmolytic, diuretic, estrogenic, anticoagulant, antifungal, antiviral, anti-helminthic, antimicrobial, hypothermal, anti-tubercular, anti-HIV, herbicidal, anticonvulsant and analgesic activity. This review has summarized an overview of general strategies that allow the design of 4H-pyran derivatives via catalyzed one-pot multicomponent reactions.

N-Acylhydrazone Pharmacophore's Analgesic and Anti-inflammatory Profile: Recent Advancements during the Past Ten Years.

Due to its important biological and pharmacological properties, in the field of medicinal chemistry and drug discovery, the N-acylhydrazone motif has shown to be extremely adaptable and promising. This scaffold has become a crucial component in the synthesis of numerous bioactive agents. N-Acylhydrazones are also interesting biological and synthetic tools due to their easy and straightforward synthesis. The current review provides a summary of the analgesic and anti-inflammatory activities of N-acylhydrazone derivatives over the past ten years. A brief discussion of structure-activity relationships is also provided which may guide researchers in medicinal chemistry to develop derivatives based on N-acylhydrazone scaffold as potent anti-inflammatory candidates.

A Comprehensive Review on Trigonella foenum-graecum L. with Special Reference to Unani Medicine.

Trigonella foenum-graecum L., commonly known as Ḥulba or Methi in Unani medicine, is an annual self-pollinating plant belonging to the Leguminosae family. It has been utilized for centuries to treat a wide range of diseases, and modern research has supported its traditional medicinal claims. In this study, the authors have conducted manual and online searches to gather and summarize the scientific literature on Ḥulba. This article seeks to underscore the potential of Ḥulba in addressing a variety of health conditions as identified by esteemed classical Unani scholars, as well as to investigate its phytochemistry and pharmacological properties in contemporary medicine. The authors have utilized electronic databases, such as PubMed, Science Direct, DOAJ, Google Scholar, and Ayush Research Portal to filter published material. According to the gathered literature, Unani physicians have consistently recommended Ḥulba seeds for a variety of ailments, such as indigestion, flatulence, colitis, arthritis, backache, paralysis, headaches, common cold, cough, bronchial asthma, diabetes mellitus, vitiligo, and pityriasis. Additionally, the seeds and green leaves of Ḥulba contain several chemical constituents, such as alkaloids, flavonoids, steroids, saponins, and amino acids. Furthermore, several pharmacological studies have demonstrated that Ḥulba possesses various properties, including antidiabetic, antispasmodic, hypolipidemic, immunological, antibacterial, anthelmintic, antiinflammatory, analgesic, and antioxidant activities. Based on the available evidence, it can be concluded that Ḥulba has been effectively used in Unani medicine for treating a wide range of diseases. Unani scholars have extensively documented its pharmacological properties, which have been supported by modern research studies. However, further research is necessary to validate some of the claims made in traditional medicine using scientific parameters.

Применение психотропных препаратов в соматической медицине (Обзор литературы)

In the early stages of the development of psychiatry, all new psychotropic drugs, without any exception, came to it from other areas of medicine. Examples are chlorpromazine (came from anesthesiology, where it was used for so-called potentiated anesthesia), reserpine (came from cardiology, where it was used as a treatment for arterial hypertension), lithium (came from rheumatology, where it was used to treat gout, long before John Cade), iproniazid (originally a promising anti-tuberculosis drug), methylene blue (came from parasitology, where it was used to treat malaria), sulpiride (was discovered in the process of searching for a new antiarrhythmic among procainamide analogues). Now the situation has turned 180 degrees. The arsenal of psychotropic drugs at the disposal of psychiatrists today had expanded unimaginably, compared to the 1950s. And many of these drugs, in addition to their main psychotropic activity, have a number of additional somatotropic properties that are of genuine interest to researchers from various fields of medicine. Within the framework of this article, we decided to focus not on rather banal and already widely known properties of some psychotropic drugs, such as analgesic, antiemetic, prokinetic, antipruritic or antimigraine activity, but on unexpected and sometimes surprising properties, such as their antitumor activity against some tumors of the central nervous system, their antifungal, antibacterial, antiviral activities.

Nature's Gift: Syzygium Aromaticum

From ancient times to now, cloves have been utilized in traditional and culinary practices. Syzygium aromaticum, also known as clove, is extracted from the buds of a flowering plant that belongs to the Myrtaceae family. This oil comprises 85% Eugenol (4-allyl-2-methoxyphenol), 5.5% Eugenyl acetate, and 1.5% β-caryophyllene. S. aromaticum is known for its antibacterial, antiviral, antioxidant, and anti-inflammatory properties. S. aromaticum has multiple beneficial effects, including antifungal, antiemetic, antispasmodic, analgesic, antiseptic, anticarcinogenic, antiallergic, and anti-mutagenic activity. However, there is a lack of comprehensive information available in the current literature. To ensure the safe and effective use of clove oil, it is important for health professionals to receive adequate training through in-service programs, symposiums, conferences, and congresses. It is crucial to remember that clove oil contains powerful chemical compounds, and uncontrolled use may result in harm. Therefore, it should only be used under the supervision of a health team. It is recommended to raise public awareness about the proper use of clove oil by health professionals.

Targeting the facilitatory effect of cAMP on HCN2 channel opening promotes analgesic actions

Targeting the facilitatory effect of cAMP on HCN2 channel opening promotes analgesic actions

Synthesis and Antimicrobial and Analgesic Activity of Products of the Recyclization of 5-(Het)Aryl-4-(trifluoromethyl)furan-2,3-diones under the Action of Aromatic Amines

Synthesis and Antimicrobial and Analgesic Activity of Products of the Recyclization of 5-(Het)Aryl-4-(trifluoromethyl)furan-2,3-diones under the Action of Aromatic Amines

Exploring new imines as anti-inflammatory COX and 5-LOX inhibitors with an improved pharmacokinetic profile.

Background: Dual COX/5-LOX inhibition is a bright strategy for developing new potent and safe anti-inflammatory agents. Methods: New imines were synthesized and evaluated for their anti-inflammatory activity. The most active compounds were further investigated for their safety profile. Their molecular docking and physicochemical parameters were assessed. A new LC-MS/MS method was developed for the quantification of compound 4d in rat plasma. Results: Synthesized compounds were found to have anti-inflammatory activity (77-88% edema inhibition). In addition, 4d, 5m and 7d showed analgesic activity (92.50, 95.71and 96.28% protection, respectively). 4d showed dual COX-2/5-LOX activity. Molecular docking expected the binding pattern of compounds in COX-1, COX-2and 5-LOX active sites. The in vivo pharmacokinetic parameters of compound 4d were also obtained.

Investigations of new N1-substituted pyrazoles as anti-inflammatory and analgesic agents having COX inhibitory activity.

Background: The search is ongoing forideal anti-inflammatory and analgesic agents with promising potency and reasonable selectivity. Methods: New N1-substituted pyrazoles with or without anacetamide linkage were synthesized and evaluated for their anti-inflammatory and analgesic activities. COX inhibitory testing, molecular docking, molecular dynamics simulation and antiproliferative activity assessmentswere performed. Results: All compounds exhibited anti-inflammatory activity up to 90.40% inhibition. They also exhibitedgood analgesic activity with up to 100% protection. N1-benzensulfonamides 3d, 6c and 6h were preferentially selective agents towardCOX-2. Compound 3d showed good cytotoxicity against MCF-7 and HTC116 cancer cell lines. Molecular modeling studies predicted the binding pattern of the most active compounds. Molecular dynamics confirmed the docking results. All compounds showedremarkable pharmacokinetic properties.