Synthesis and anti-inflammatory, analgesic, and anti-ulcerogenic bioevaluation of new indole bioconjugates

Objectives: This present study was envisaged to identify the effect of analgesic and anti-inflammatory activity forethanolic root extract of Allium cepa L. Methodology: The study was carried out using Sprague- Dawley rats (250- 300g) and Albino mice (25- 30g). Diclofenac sodium and Tramadol are the standard drugs, was prepared by dissolving in distilled water to make the concentration of 10mg/kg and 20mg/kg for anti-inflammatory and analgesic activity respectively. The effect of ethanolic extract of A.cepa L root was investigated for analgesic activity using tail immersion method. The anti-inflammatory activity of ethanolic root extract of A.cepa was studied using carrageenan-induced paw edema to the rats.Results: The anti-inflammatory activity was evaluated using carrageenan method in Sprague- Dawley rats. The anti-inflammatory activity was found to be dose dependent in carrageenan induced paw edema model. The ethanolic extract has shown highly significant (p<0.001) percentage of inhibition of paw edema, 57.43% and 60.56% at 5th hour at the low dose and high dose, respectively. Whereas analgesic activity was studied using tail immersion method in mice. The ethanolic root extract was shown highly significant (p<0.001) analgesic activity with standard drug and high dose but, low dose showed less significant (p<0.05) analgesic activity. Conclusions: The findings of the present study concluded that A.cepa L roots have potential to treat pain and inflammation and as a good source, novel natural analgesic and anti-inflammatory agents. The ethanolic extract of A.cepa L root showed highly significant analgesic and anti-inflammatory activity in mice and rats respectively.

This study was aimed to design novel diclofenac hydrazones having anti-inflammatory and analgesic activity with gastric sparing effect. A new series of 2-[2-(2,6-dichloroanilino)phenyl]-N’-[(substituted phenyl) methylidene] acetohydrazide derivatives (1−14) were synthesized and evaluated for their anti-inflammatory, analgesic, and ulcerogenic activity. The compounds were identified and confirmed by elemental analysis and spectral data. During anti-inflammatory activity by carrageenan-induced paw edema method, compounds (2, 3, 7, 8, 11, and 13) were found to be most promising. Compounds 3, 8, and 13 have been found to have significant analgesic activity compared to the reference drug diclofenac in analgesic activity by both the hot plate method and acetic acid-induced writhing method. The compounds which presented highly significant anti-inflammatory and analgesic activity were further tested for their ulcerogenic activity. Compounds 3 and 8 showed maximum ulcerogenic reduction activities. Compound 8 was found to have LD50 of 168 mg/kg. Compound 8 with 3,5-dimethoxy-4-hydroxyphenyl substitution was found to be the most promising anti-inflammatory and analgesic agent with gastric sparing activity. Molecular docking of compounds was performed for COX−1/COX−2 binding site. Lead compound 8 showed better binding affinities of −9.4 kJ/mol with both COX-1 and COX-2 as compared to the standard drug, diclofenac with binding affinities of −6.6 kJ/mol and −8.1 kJ/mol for COX−1 and COX−2, respectively.

Aim: The reactions were carried out by one pot three-component synthesis, 3- cyanoacetylindole (1) on reaction with aromatic aldehydes (2) and β-naphthol (3) in an aqueous medium in the presence of L-proline as a catalyst under reflux for 30 min, resulting in (3-amino-1- phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl)methanone (4). The method has many advantages like short reaction times, good yields, and simple workup procedure, besides being green in nature. Pharmacological evaluation of title compounds was done for anti-inflammatory and analgesic activities. Anti-inflammatory activity was carried carrageenan-induced paw edema model in which indomethacin was used as standard and analgesic activity was evaluated by eddy's hot plate method using diclofenac as standard drug. Background: Benzopyrans or chromenes are an important class of heterocyclic compounds due to their broad spectrum of biological activity and a wide range of applications in medicinal chemistry. The chromene moiety is found in various natural products with interesting biological properties. Chromenes constitute the basic backbone of various types of polyphenols and are widely found in alkaloids, tocopherols, flavonoids, and anthocyanins. Indoles are omnipresent in various bioactive compounds like alkaloids, agrochemicals, and pharmaceuticals. Objective: The objective of this study is to synthesize one-pot stepwise Green synthesis, antiinflammatory and analgesic activities of 3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3- yl) methanones. Methods: The acute anti-inflammatory effect was evaluated by carrageenan-induced mice paw edema (Ma Rachchh et al., 2011). Edema was induced by injecting carrageenan (1% w/v, 0.1 ml) in the right hind paw of mice. The test compounds 1-12, indomethacin (10 mg/kg), and the vehicle were administered orally one hour before injection of carrageenan. Paw volume was measured with a digital plethysmometer at 0, 30, 60, 90, 120 min after injection. Percentage increase =A-B/ A *100 Results: Carrageenan induced paw edema model was used for anti-inflammatory activity in which animals treated with standard (indomethacin) and test compounds showed a significant decrease in the paw edema. Analgesic activity was estimated using Eddy’s hot plate method; animals were treated with standard (diclofenac) and test compounds showed a significant increase in the reaction time. Conclusion: A green, one-pot, step-wise and three-component synthesis of 3-amino-1-phenyl-1Hbenzo[ f]chromen-2-yl) (1H-indol-3-yl) methanone was achieved by using water as a solvent, Lproline as catalyst under reflux conditions. The reactions were carried out in eco-friendly conditions with shorter reaction times, easier workup, and high yields. Anti-inflammatory activity was evaluated by carrageenan-induced paw edema model, where significant anti-inflammatory activity is shown by all the test compounds 4(a-l) compared to standard drug. Analgesic activity was studied by Eddy’s Hot plate method and Test compounds 4e, 4f, 4h, 4i, 4j, 4k, 4l showed significant activities compared to the reference drug.

Imidazole moieties exhibit a broad range of biological activities, including analgesic, anti-depressant, anticancer, anti-fungal, anti-tubercular, anti-inflammatory, antimicrobial, antiviral, and antifungal properties. In this study, we explored the use of Schiff base for the synthesis of new imidazole derivatives as anti-inflammatory and pain-relieving agents. A series of eight novel imidazole analogues (2a–h) were prepared in three steps with excellent yields. All compounds were characterized using IR, NMR, and mass spectral data. Their analgesic and anti-inflammatory activities were evaluated using hot plate and paw oedema methods. Compound 2 g (1-(2,3-dichlorophenyl)-2-(3-nitrophenyl)-4,5-diphenyl-1H-imidazole) showed significant analgesic activity (89% at 100 mg/kg b.w.), while compounds 2a (2-(2,6-dichlorophenyl)-1-(4-ethoxyphenyl)-4,5-diphenyl-1H-imidazole) and 2b (2-(2,3-dichlorophenyl)-1-(2-chlorophenyl)-4,5-diphenyl-1H-imidazole) exhibited good anti-inflammatory activity (100% at 100 mg/kg b.w.), comparable to diclofenac salt (100% at 50 mg/kg b.w.). Molecular docking studies were conducted using Schrödinger software version 2021-2, employing the OPLS4 force field for both receptor and ligand preparation. The results were visualized using molecular visualization software such as PyMOL. These studies revealed that compound 2g exhibited the highest binding affinity with the COX-2 receptor (−5.516 kcal/mol). Compound 2g formed three conventional hydrogen bonds with residues GLN-242 (bond length: 2.3 Å) and ARG-343 (bond lengths: 2.2 Å & 2.4 Å). This binding affinity was comparable to that of Diclofenac salt, which showed the highest binding affinity of −5.627 kcal/mol with the COX-2 receptor. Diclofenac salt formed two conventional hydrogen bonds with the residues ARG-344 (bond length: 2.0 Å) and TRP-140 (bond length: 1.7 Å). Later, molecular dynamic simulations confirmed the stable binding affinity of compound 2g with the protein. Furthermore, other compounds also demonstrated potential binding to the receptor-binding pocket region. The anti-inflammatory potential of the synthesized compounds was evaluated using the carrageenan-induced rat hind paw oedema model, while the analgesic potential was assessed using the hot plate method. These evaluations were conducted in comparison with Diclofenac sodium, serving as the standard compound. However, compound 2g stood out for its superior analgesic activity, as confirmed by in-vivo examination. These findings suggest that these novel imidazole derivatives have potential as anti-inflammatory and analgesic agents.

Aim: The ethanolic, ethyl acetate, and hexane extracts of Nymphoides hydrophylla at the doses of 250 mg/kg and 500 mg/kg were administered for the evaluation of analgesic and anti-inflammatory activities (both in vitro and in vivo). Materials and Methods: Analgesic activity was evaluated by acetic acid-induced writhing, tailflick method, and Eddy’s hot plate method in albino rats. Paracetamol and tramadol were used as a standard reference drugs for analgesic activity. In vitro anti-inflammatory activity was evaluated by Human red blood cell membrane stabilization method and protein denaturation method. In vivo anti-inflammatory activity was evaluated by carrageenan-induced paw edema in albino rats. Diclofenac sodium was employed as reference drugs for antiinflammatory studies. Results and Discussion: The administration of ethanolic, ethyl acetate, and hexane extracts of N. hydrophylla in rats with 250 and 500 mg/kg body weight (b.wt.) reduced pain and inflammation, indicating that ethanolic extract possesses better analgesic and anti-inflammatory activities compared to other two extracts. The maximum analgesic and anti-inflammatory activities were observed in rats receiving 500 mg/kg b.wt. of N. hydrophylla ethanolic extract. Conclusion: Our study indicates that N. hydrophylla extracts possess both antiinflammatory and analgesic activities and it may be useful as an anti-inflammatory agent in inflammation-related disorders.

Otostegia fruticosa is traditionally used to treat tonsillitis, stomach ache, asthma, arthritis, and febrile illness in different parts of Ethiopia and other countries. In this experiment 70% ethanolic crude extract and fractions of the leaf of Otostegia fruticosa (Forssk.) Schweinf. ex Penzig were evaluated for their in-vivo anti-inflammatory and analgesic activities and in-vitro hyaluronidase inhibition properties at different concentrations. Tail immersion, acetic acid induced writhing and carrageenan-induced paw edema model were used to assess the in-vivo analgesic and anti-inflammatory activities, respectively. Swiss albino mice of either sex were randomly divided into five groups of six mice per group and for evaluation of the fractions randomly divided into six groups of six mice per group. The test groups were treated with hydroalcoholic extract of Otostegia fruticosa (O. fruticosa) at doses of 100, 200, and 400 mg/kg. The positive control groups received either pethidine 5 mg/kg or aspirin at 100 mg/kg or 150 mg/kg. The negative control groups were orally given sunflower oil. All the fractions were administered at the dose of 400 mg/kg. In all models, the higher dose (400 mg/kg) of the crude extract and chloroform fraction showed a significant central and peripheral analgesic and anti-inflammatory activities with comparable effects to standards used. The hyaluronidase inhibition assay result showed that the test samples displayed concentration-dependent inhibitory activities. These findings indicate that 70% ethanol extract and organic solvent fractions of O. fruticosa leaves have potential analgesic, anti-inflammatory, and enzyme inhibitory activities.

Anti–inflammatory, analgesic and antipyretic activity of methanolic Tecomaria capensis leaves extract

The utilization of purified roots from Plumbago zeylanica in traditional Ayurvedic medicine for addressing various inflammatory conditions such as arthritis prompted this study to explore the in vitro anti-inflammatory potential of distinct extracts derived from these roots. Additionally, the study assessed the anti-inflammatory and analgesic activities of the most potent extract in Wistar rats (either sex) and predicted the bioactive phytoconstituents through in silico molecular docking with the cyclooxygenase-II enzyme. The purification of the plant material involved the traditional detoxification process of shodhana. The purified roots underwent hot continuous extraction (Soxhlet extraction) to produce extracts with increasing polarity. The in vitro anti-inflammatory activity of these extracts, at varying concentrations, was evaluated through assays measuring the inhibition of albumin denaturation and hypotonicity-induced hemolysis. Analgesic activity and anti-inflammatory activities were assessed in rats through formalin-induced pain and carrageenan-induced paw edema models, respectively. Prediction of bioactive compounds was conducted through molecular docking and dynamics of different phytoconstituents of the purified roots of P. zeylanica with the cyclooxygenase-II (COX-2) enzyme. In vitro studies demonstrated the anti-inflammatory effects in different extracts, methanolic extract being the most potent. In vivo studies revealed analgesic and anti-inflammatory activities in the methanolic extract. Molecular docking results indicated good interaction between phytoconstituents of the methanolic extract and COX-2 enzyme, with chitranone being the most inhibiting compound having stable ligand anchoring. The study concludes that the methanolic extract of purified roots of P. zeylanica possesses notable anti-inflammatory and analgesic activities, potentially attributed to the presence of its COX-2 inhibitor compounds.

Purpose: To investigate the analgesic and anti-inflammatory activities of two herbal polymedicines - Aujaie and Surangeen to ascertain their therapeutic claims. Methods : A total of 96 rats were divided into two equal groups; one for determination of antiinflammatory activity and the other for analgesic activity. Anti-inflammatory and analgesic activities were evaluated by carrageenan-induced paw edema and formalin-induced paw licking test, respectively. For both studies, group I (untreated control) received 1 ml/kg, (po) of gum suspension 1 h before carrageenan injection. Aspirin (100 mg/kg, po) was given to group II (treated control) before injection. Groups III, IV and V were administered orally aujaie (3, 4 and 5 mg/kg, po, respectively), while surangeen tablets (10, 20 and 40 mg/kg, po) were given to groups VI, VII and VIII, respectively. Pain was experimentally induced by injecting 0.1 ml of 2.5 % formalin (40 % formaldehyde in distilled water) via the subplantar region of the left hind paw. Results : Significant (p < 0.05) anti-inflammatory activity for aspirin (group II as well as for groups III - VIII with paw edema inhibition (PDI) ranging from 24.6 - 90.2 %, There was significant ((p < 0.05) analgesic activity in group II, VI and VII while in groups III - V and VIII the activity was insignificant (p < 0.05). Conclusion: Aujaie and surangeen tablets exhibited pronounced analgesic and anti-inflammatory activities in rats depending on the dose employed. Keywords : Aujaie, Surangeen, Anti-inflammatory, Analgesic.

Pharmacological activity and flavonoids constituents of Artemisia judaica L aerial parts

Background: Various inflammatory mediators are involved in initiating and sustaining pain/inflammation cascade. Recently, leukotrienes (LTs) have been shown to be important mediators in pain and inflammation. Aims and Objective: An experimental evaluation of analgesic, anti-inflammatory, and antipyretic activity of LT receptor antagonist-montelukast. Materials and Methods: Wistar rats of either sex weighing 180-250 g and Swiss mice weighing 25-30 g were used. Analgesic activity of montelukast (20 mg/kg) was evaluated and compared with tramadol (10 mg/kg) and aspirin (300 mg/kg) using tail flick response method and acetic acid-induced writhing method. For evaluating anti-inflammatory activity, carrageenin-induced rat paw edema and formalin-induced arthritis models were used. The antipyretic activity was evaluated in Baker’s yeast-induced pyrexia in rats. Results: Montelukast (20 mg/kg) had significant analgesic activity compared to control in acetic acid-induced writhing model but was ineffective in tail flick model. Montelukast showed significant anti-inflammatory activity in carrageenin-induced paw edema and formalin-induced arthritis models. Montelukast did not show antipyretic activity. Conclusion: Montelukast shows anti-inflammatory and analgesic activity which needs substantiation.

Aroylpropionic acid based 2,5-disubstituted-1,3,4-oxadiazoles: Synthesis and their anti-inflammatory and analgesic activities

In the present work, Caesalpinia bonduc seed coat extract (CBSCE) has been evaluated for anti-inflammatory and analgesic activity C. bonduc seeds have been attributed with anti-inflammatory and analgesic properties in the folklore medicine. Here in our study, we have tried to carry out the systematic evaluation of the seed coat extract of C. bonduc to substantiate these claims. C. bonduc seed coat was extracted with 95% ethanol and concentrated; further, the extract was screened for anti-inflammatory and analgesic activity. The studies were carried using Carrageenan-induced Paw Edema, Egg albumin-induced paw edema, Eddy's Hot Plate Test, Tail Immersion Method so as to prove acclaimed properties. The data was analyzed statistically by Students’ ‘t’ test. The results indicate that seed coat extract has the ability to decrease the induced inflammation at varied doses in Carrageenan model as well as in the Egg albumin model in rats. The antinociceptive results indicate that the extract has the ability to increase the pain threshold of the animals and reduce the pain factor, thereby inducing analgesia. Thus, it can be concluded that CBSCE posses analgesic and anti-inflammatory activity.

Analgesic, anti-inflammatory and anti-pyretic activities of n-hexane and aqueous ethanolic extracts of Malva neglecta in Swiss albino mice was evaluated. For each activity, the mice were divided into 4 groups: Group 1 served as control, Groups 2 and 3 were given n-hexane and aqueous ethanol extracts, respectively whereas Group 4 was treated with the standard drug. Analgesic activity was evaluated against acetic acid induced writhing, Eddy's hot plate method, and Formalin induced paw licking. Anti-inflammatory activity was evaluated by carrageenan-induced paw edema. The extracts were also examined for their anti-pyretic activities against yeast-induced pyrexia. Results showed that the n-hexane (p &lt; 0.05) and aqueous ethanolic (p &lt; 0.005) extracts of M. neglecta exhibited analgesic activity by reducing acetic acid-induced writhing, mean reaction time on hot plate model and formalin-induced paw licking in mice as compared to the control. The n-hexane extract (p &lt; 0.05) as well as aqueous ethanolic (p &lt; 0.005) extracts produced significant antiinflammatory activity as compared to the control. Both the n-hexane and aqueous ethanolic extracts revealed significant antipyretic activity (p &lt; 0.005 and p &lt; 0.05, respectively) in mice model. The results of the present study demonstrated that the n-hexane and aqueous ethanol extracts of M. neglecta possess analgesic, antiinflammatory and anti-pyretic activities. Bangladesh J. Bot. 50(3): 577-583, 2021 (September)

Design, synthesis, biological evaluation, and comparative Cox1 and Cox2 docking of p-substituted benzylidenamino phenyl esters of ibuprofenic and mefenamic acids