Reference Drugs Aspirin Research Articles

HPLC analysis and anti-inflammatory, antinociceptive, healing and antidepressant properties of Anchusa italica Retz extracts

BackgroundIn traditional herbal medicine, Anchusa italica has sometimes been used to treat inflammatory diseases, wounds and sooth pain, but the scientific evidence supporting these uses is not solid. Given its traditional uses, we aim to evaluate the anti-inflammatory, antinociceptive, healing and antidepressant pharmacological activities of root and leaf extracts from the A. italica. Methodsthe phytochemical study was carried out by HPLC-MS analysis. The anti-inflammatory, antinociceptive and antidepressant activities were studied on male Wister rats, and healing activity on mal New Zealand rabbits. Extracts were administered orally using doses 200 and 400 mg/kg for anti-inflammatory activity, 400 mg/kg for analgesic activity, 200 mg/kg for antidepressant activity. Healing activity was studied using a cream containing 5 % of the extract topically. ResultsThe HPLC analysis found six phenolic compounds in the root extract and nine in the leaf extract. The anti-inflammatory test gave significant results (p < 0.001), at 400 and 200 mg/kg doses, the leaf extract recorded a percentage of inhibition of (82.89 % and 69.73 % respectively, while the root extract gave a percentage of inhibition of 73.67 % and 65.78 % respectively. The analgesic test also showed a significant (p < 0.001), the rats treated with the extract of the leaves have a number of abdominal contractions (11.33 ± 0.94) very close to that of reference drug aspirin (10.33 ± 0.47). In antidepressant activity, the immobility time recorded in rats treated with leaf extract was 81.86 ± 3.71 and 86.8 ± 4.65 s for root extract. The healing test showed that the root extract was effective (p < 0.05) for the treatment of the burns, after 20 days of treatment, the percentage of contraction (100 %) was recorded in the extracts 5 % and madecassol compared to the negative control 89.51 ± 4.08 %. ConclusionThese results confirm the plant's traditional use in the treatment of inflammatory diseases, wounds and pain.

Anti-Nociceptive Properties of Methanolic Extract of Artocarpus altilis (Breadfruit) on Wistar Rats in Mechanical Model of Pain Study

Flavonoids has been shown to have anti-inflammatory and anti-oxidant properties, which may have potential protective effects against mechanical induced models of pain. In this context, administering methanolic extract of artocarpus altilis (MEAA) during the experimental rats could potentially increase the pain threshold, which could in turn, increase the quality of health and life expectancy. Dearth literature exists on the analgesic effects of Bread fruit on pain. Hence, this study aims at investigating the potential anti-nociceptive properties of MEAA to increase paw withdrawal latency using murine model. 25 Wistar rats were randomly selected into five groups: Group 1=(control); Group 2, 3 &amp; 4 (100, 200, 300-mg/kg MEAA, respectively) and Group 5=100-mg/kg Aspirin (ASP). The rats were subjected to mechanical pain-behavioral studies at 30, 60, 10 and 120 minutes after administration of test substances. Results obtained showed that, at 30 minutes post administration of MEAA and ASP, significant increase (p&lt;0.05) in pain threshold was observed in 100, 200, 300-mg/kg and ASP groups when compared to control. At 60 minutes, significant increase (p&lt;0.05) in pain threshold was observed in 200, 300-mg/kg and ASP groups when compared to control. Finally, at 90- and 120-minutes, significant increase (p&lt;0.05) in pain threshold was observed in 300-mg/kg group only, when compared to control. In conclusion, graded doses of MEAA showed analgesic properties by increasing pain threshold when administered 30, 60, 90 and 120 minutes prior to subjection of the animals to mechanical pain. Therefore, MEAA have shown analgesic properties that could even be more effective than the reference drug (aspirin).

Rational design, synthesis and SAR study of novel warfarin analogous of 4-hydroxy coumarin-beta-aryl propanoic acid derivatives as potent anti-inflammatory agents

Synthesis of highly potent and enhanced safety profiled antiinflammatory drugs has become a challenging task in the drug discovery process. A library of warfarin analogue 3-(4‑hydroxy-2-oxo-2H-chromen-3-yl)-3-arylpropanoic acid derivatives have been synthesised and their structures were established by availing different analysis techniques. The invitro COX-1/COX-2 study revealed the effective potency of the selective compounds 2b(IC50=180.45 µl/ml), 2c(IC50=21.03 µl/ml) and 2f(IC50=120.45 µl/ml) against COX-2 compared to reference drug aspirin (IC50=121.60 µl/ml). Compound 2c is more selective towards COX-2 with a high selective index of 7.42 than standard aspirin with a selective index of 4.14. Further, the target molecules were assessed for their antiinflammatory activity against MMP2 and MMP9, the results revealing a high percentage of inhibition. While, protein denaturation study displayed high potency of the compounds 2a (IC50=13.32 µg/ml), 2 g (IC50=11.14 µg/ml) and 2l (IC50=4.71 µg/ml) as compared with aspirin (IC50=13.42 µl/ml). The docking studies were established to understand the structural features responsible for biological activity and the outcome of the docking studies are indeed following the experimental results.

Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs.

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

Protective effect of methanol extract of latex of Calotropis procera in an experimental model of colorectal cancer

Ethnopharmacological relevanceThe plant, Calotropis procera, has been used for treating various gastrointestinal disorders and cancer. Some of these medicinal properties have been attributed to the latex produced by the plant. Aim of the studyTo evaluate the efficacy of methanol extract of air-dried latex (MeDL) of C. procera in the rat model of colorectal cancer (CRC). Materials and methodsCRC was induced in the rats by 1,2-dimethylhydrazine (DMH) and the effect of MeDL was evaluated at two doses (50 and 150 mg/kg). MeDL and reference drug aspirin (60 mg/kg) were administered orally starting from 1 h before injecting DMH till 8 weeks after the second dose of DMH. The study also included experimental and normal control groups. Microscopic analysis was carried out to determine the count for aberrant crypt foci (ACF) and histology score whereas enzyme-linked immunosorbent assay and immunohistochemical analyses were performed for markers of carcinogenesis and angiogenesis. Other parameters that were evaluated include deoxyribonucleic acid (DNA) fragmentation, laddering, Bcl2 and Bax immunoreactivity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity. ResultsSubcutaneous injection of DMH induced pre-neoplastic changes in the colon of rats with the appearance of ACF with multiple crypts (1–3, 4–6 or >6). In the experimental control group, total ACF count was 3.49 ± 0.23/cm of the colon length and the median histology score was 2.0 for architectural abnormalities, 2.0 for dilatation of crypts and 1.5 for hyperplasia/dysplasia against 1.0 for all the characteristics in normal rats. Oral administration of MeDL similar to aspirin, led to a reduction in ACF count and histology score of CRC concomitant with a decrease in the levels of markers of carcinogenesis - β-catenin and proliferating cell nuclear antigen (PCNA); markers of angiogenesis - matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF), and an increase in apoptotic DNA fragmentation. ConclusionMeDL confers protection in the rat model of CRC and the study suggests its therapeutic potential in this condition.

Study of analgesic and anti-inflammatory activity of dry extract from sakhalin willow shoots

One of the important treatment landscape widely used for the various disease’s management is phytotherapy, or treatment with herbal medicines. Phytotherapy is used as an independent type of treatment in most cases, and in combination with other drugs as additional treatment. The pain and inflammation control continue as long as there is humanity itself. With old experience of traditional medicine know that Salicaceae have a pronounced anti-inflammatory and analgesic effects. The pharmacological study of the dry extract from Sakhalin willow shoots – the study of analgesic and anti-inflammatory activities in different pharmacological models – was the aim of this work.&#x0D; The analgesic and anti-inflammatory activity of the standardized dry extract from Sakhalin willow shoots (DESWS) was experimentally researched. The study of pharmacological activities of DESWS was carried out at the Educational and Scientific Institute of Applied Pharmacy of the National University of Pharmacy (Kharkov). The effect of DESWS on the course of the inflammatory process was studied in a model of carrageenan edema. Analgesic activity was studied in a model of thermal irritation in white male rats.&#x0D; The study of anti-inflammatory activity in rats on a model of carrageenan edema showed that an effective dose of the studied extract was 30 mg/kg. The greatest reduction in paw edema in rats on the model of carrageenan edema in the first hour of the experiment was observed in the group of animals treated with DESWS at a dose of 30 mg/kg. The anti-inflammatory activity of DESWS was 53.74%, but it was slightly inferior than in the reference drug Diclofenac.&#x0D; It was found that DESWS also shows pronounced analgesic properties at a dose of 30 mg/kg during the first and second hours of the experiment in the model of the limb’s thermal irritation «Hot Plate» in rats. After 120 minutes of experiment the studied activity didn’t change significantly and remained at the level 62.6%. The analgesic effect of DESWS was inferior to antinociceptive activity of the reference drug Metamizole sodium and superior to the studied activity of the reference drug Aspirin.&#x0D; Thus, the dry extract from the Sakhalin willow shoots can affect both pain and inflammation, and it is a potential remedy for further pharmacological research.

Antipyretic potential of dichloromethane leaf extract of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) in rats models

IntroductionFever is managed using synthetic drugs such as aspirin, paracetamol among others. Synthetic drugs are associated with many side effects. Herbal medicines form alternative therapy since they possess fewer side effects and are readily available. This study aimed to determine antipyretic potential of DCM extracts of E. globulus and S. didymobotrya in Swiss albino rats. Materials and methodsThe plant leaves samples were obtained from Embu County, Kenya. Dichloromethane solvent was used to extract bioactive constituents from the plant samples. Three grams of DCM leaf extracts of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) samples were obtained and analyzed to determine quantitative phytochemical composition at ICIPE laboratory using GC-MS. Albino rats were used in the antipyretic activity study. Nine groups of five experimental animals were used in each test: Positive control, normal control, negative control and experimental (25, 50, 100, 150, 200 and 250 mg/kg body weight extracts) groups. Pyrexia was induced by injection of turpentine in albino rats intraperitoneally. One hour later, the pyretic animals received the leaf extracts at various dose levels, reference drug (aspirin100 mg/kg body) or the vehicle (DMSO). ResultsResults of antipyretic in vivo bioscreening revealed that E. globulus and S. didymobotrya possess potent antipyretic activity which was comparable to that of the reference drug aspirin. Both extracts exhibited highest antipyretic activity at a dose of 250 mg/kg bw. Results of the GC-MS revealed that these plants possess bio-compounds such as Terpinolene, Alpha-pinene, Borneol, Globulol and Terpineols that are associated with antipyretic activity. ConclusionsIn conclusion, this study revealed that these plants are endowed with bioactive compounds such as terpenoids, and flavonoids that possess antipyretic activity in rats.

Synthesis and in vitro activities on anti-platelet aggregation of 4-methoxy-1,3-phthalamidesamides and benzenedisulfonamides

Cardiovascular diseases are the most frequent cause of morbidity and mortality worldwide. In order to discover novel compounds with anti-platelet aggregation activities, a series of novel 4-methoxy-1,3-phthalamidesamides (1a–1i) and a series of novel 4-methoxy-1,3-benzenedisulfon-amides (2a–2i) were synthesized and their anti-platelet aggregation activities were evaluated by the turbidimetric method in response to the following agonists: adenosine diphosphate (ADP), arachidonic acid (AA), and Collagen. Those compounds that have better in vitro activities were subjected to cell toxicity tests via cell counting kit-8 (CCK-8) assay. The inhibition rates of anti-platelet in vitro of five compounds 1g (39.45%), 2d (38.87%), 2g (38.55%), 2h (44.56%), and 2i (43.93%) were higher than that of two reference drugs picotamide (36.12%) and aspirin (38.45%) when ADP was selected as an inducer. The inhibition rates of seven compounds 1c (43.63%), 1d (40.02%), 1g (47.42%), 1i (40.45%), 2c (40.11%), 2d (40.45%), and 2i (49.05%) were higher than that of picotamide (34.89%) and aspirin (39.43%) when AA was selected as inducer. And the inhibition rates of five compounds 1d (47.22%), 1i (45.01%), 2d (38.74%), 2e (42.21%), and 2f (39.94%) were higher than picotamide (38.45%) and aspirin (37.08%) when collagen was selected as inducer. Moreover, the effect of cell toxicity exhibited that none of the compounds had obvious cell toxicity against L-929 cells. Therefore, 4-methoxy-1,3-phthalamidesamides (1a–1i) and 4-methoxy-1,3-benzenedisulfon-amides (2a–2i) have the potential to become a novel kind of anti-platelet drugs and deserve further study.

Effects of Nothrombel on Thrombin-Induced Formation of Thrombocyte-Leukocyte Complexes

The effects of Nothrombel on the thrombin-induced formation of thrombocyte-leukocyte complexes (TLC) were studied. Nothrombel was found to produce dose-dependent inhibition of TLC formation. Its activity was greater than that of reference drug aspirin. The 50% inhibition constant (EC50) of Nothrombel was 1.75 μmol/ml, compared with greater than 1.75 μmol/ml for aspirin. The mechanism of inhibition of TLC formation by Nothrombel relates to the ability of this drug to suppress the expression of P-selectin by thrombocytes and the membrane complex GPIb-IX-V on membranes and the mobilization of cytoplasmic calcium in thrombocytes, and, evidently, an inhibitory action on the P2Y12 purine receptors of thrombocytes.

Antioxidant, anti-inflammatory and antinociceptive activities of methanolic extract of Justicia secunda Vahl leaf

Background of studyPlants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. AimThe study evaluated the in vitro antioxidant, antinociceptive, and anti-inflammatory activities of the methanolic extract of Justicia secunda Vahl leaf. MethodsThe acute toxicity was performed with up and down method and the highest dose used was 2g/kg. The anti-inflammatory activity was evaluated using the carrageenan and formalin-induced paw edema models, and antinociceptive activity was evaluated using acetic acid-induced writhing reflex and tail flick test models while the antioxidant activity was evaluated using 2,2-diphenyl-2-picryl hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) photometric assay. ResultsThe extract was well tolerated as no signs of toxicity or death were noticed during the period of observation. The extract produced a concentration dependent increase in antioxidant activities in both DPPH and FRAP models. The extract produced its optimum activity at 400μg/ml in both DPPH (54.07%) assay and FRAP (1.58μM) assay. The extract produced significant (P<0.05) dose-dependent increase in both anti-inflammatory and antinociceptive activities. The antinociceptive and anti-inflammatory activities of the extract (0.4g/kg) were comparable with the reference drugs (aspirin and pentazocine) used in the study. ConclusionThis study suggests that J. secunda possesses anti-inflammatory, antinociceptive and antioxidant activities and also provide the pharmacological basis for its uses in traditional medicine for these purposes.

Synthesis and Pharmacological Evaluation of Novel Pyrazolyl Piperidine Derivatives as Effective Antiplatelet Agents

The synthesis and antiplatelet activity of substituted pyrazolyl piperidine derivatives (3a–n) are described. These compounds were synthesized by an improved ring opening reaction of 2‐arylidene quinuclidinone using hydrazine hydrate under mild conditions. They were characterized and screened for their in vitro antiplatelet profile in human platelet aggregation using adenosine diphosphate as agonist. Investigation of structure activity relation revealed interesting results. Among these synthesized derivatives (3a–n), compounds 3a, 3c, 3j, and 3l exhibited excellent activity, while 3c was the most potent one. Based on IC50 values, it was observed that most of the compounds possessed antiplatelet aggregation activity superior to the reference drug Aspirin.

Antipyretic Properties of Methanol Stem Bark Extracts of Acacia hockii De Wild and Kigelia africana (Lam) Benth in Wistar Rats

Synthetic antipyretic drugs are not readily accessible and have adverse side effects. Herbal medicines possess bioactive compounds that are safer and efficient in the management of various diseases and disorders. Acacia hockii and Kigelia africana are traditionally used to manage pyrexia among the Embu and Mbeere communities in Kenya but lack scientific data to validate their use. The present study evaluated for the antipyretic activity of the A. hockii and K. africana in rat models to scientifically validate their traditional use. The plant samples were collected with the help of local herbalists in Embu County, Kenya and transported to Kenyatta University for cleaning, air drying, milling, and extraction. Adult male Wistar rats were randomly divided into six groups of 5 animals each; normal control, positive control, negative control, and three experimental groups. The antipyretic effect was assessed using turpentine-induced pyrexia method. The antipyretic activities of the extracts were compared to reference drug aspirin. The stem bark extract of A. hockii reduced the raised rectal temperature by between 0.62-3.88% while the stem bark extract of K. africana reduced the elevated rectal temperature by between 0.06-3.07%. The reference drug aspirin reduced the rectal temperature of pyretic rats by between 0.63-3.1%. The qualitative phytochemical screening of the two extracts indicated the presence of flavonoid, alkaloids, steroids, saponins, terpenoids which are associated with the antipyretic activity. The present study demonstrated potent antipyretic activities of methanolic extracts of A. hockii and K. africana in a dose-dependent manner after the second hour of the treatment period, which supports their traditional use. The present study, therefore, recommends the ethnomedicinal use of K. africana and A. hockii in the management of pyrexia.

Synthesis, Anti-inflammatory and Anti-nociceptive Evaluation of Palmitoyl Benzamides

Purpose: To synthesize and characterize palmitoyl amino benzamides, and to evaluate them for possible anti-inflammatory and anti-nociceptive activities.Methods: Palmitoyl amino benzamides were synthesized by the opening of isatoic anhydride ring with respective amino acids (glycine, β-alanine and γ-aminobutyric acid) and the condensation of the product with palmitoyl chloride. The final products were purified on column chromatography, eluting with dichloromethane/ethyl acetate. All the compounds were unequivocally characterized using the combination of infra red (IR), 1H and 13C (nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analysis. In vivo anti-inflammatory and anti-nociceptive activities of the synthesized compounds at 20, 50 and 100mg/kg doses were carried out using carrageenan-induced paw oedema in rat and acetic acid-induced writhing in mice, respectively. Aspirin was used at a dose of 100mg/kg as the reference drug.Results: The compounds were obtained in high yield (70 – 90 %) and purity. The anti-inflammatory results showed a poor activity for the compounds except o-palmitoylamino N-carboxyethyl benzamide which produced significant inhibition (p &lt; 0.05) at a dose of 50 mg/kg (43.8 % oedema inhibition) while the reference drug, aspirin, showed 51.3 % inhibition. The anti-nociceptive study, however, showed good inhibition (p &lt; 0.05) of acetic acid-induced writhing, with o-palmitoylamino Ncarboxymethylbenzamide producing 86.2 % inhibition at 100 mg/kg dose compared with the reference drug (aspirin) which gave 74.3 % inhibition at 100 mg/kg.Conclusion: The findings of this study indicate that the synthesized compounds, though displaying poor anti-inflammatory activity, do possess promising anti-nociceptive activity.Keywords: Anti-inflammatory, Analgesic, Benzamide, Palmitoyl, Glycine, β-Alanine, γ-Aminobutyric acid, Aspirin

Four new C18-diterpenoid alkaloids with analgesic activity from Aconitum weixiense

Four new C18-diterpenoid alkaloids, weisaconitines A–D (1–4), were isolated from Aconitum weixiense. Based on extensive UV, IR, MS, 1D and 2D NMR analyses, their structures were elucidated as 8-O-ethyldolaconine (1), 4-demethylgenicunine B (2), 14-oxoaconosine (3), and 8-O-ethylaconosine (4). The analgesic activity of compound 4 was studied with CH3COOH-induced writhing model in mice. Compound 4 showed writhing inhibitions of 24% (50mg/kg), 26% (100mg/kg) and 34% (200mg/kg), respectively, as compared to the reference drug aspirin (63%) at a dose of 200mg/kg.

Antinociceptive effect of the ethanol extract of the stem bark of &lt;em&gt;Musanga cecropioides&lt;/em&gt; in mice

Musanga cecropioides R. Apud Tedlie (Cecropiaceae), also known as umbrella tree is one of the medicinal plants used in Nigeria for pain and inflammation. The stem bark was extracted with absolute ethanol and screened for analgesic activities. The screening for analgesic properties was done using: acetic acid induced writhing; formalin induced pain, tail immersion and hot plate methods all in mice. Mice were divided into five groups of five each. The first group in all models served as control and received normal saline (0.9 % NaCl), the next three groups received either 50 or 100, 200 and 400 mg/kg of the extract. The 5th group was given a reference drug either pentazocine (10 mg/kg) or aspirin (100 mg/kg). The extract at 50,100 and 200 mg/kg showed a dose dependent significant reduction of the number of writhes (p&lt;0.05, p&lt;0.05 and p&lt;0.0001 respectively) compared with the control. The extract also showed a non-dose dependent significant reduction of the paw licking time in the formalin-induced pain test with more prominence in the second phase. A significant increase in the mean reaction time of mice in the tail immersion and hot plate tests (p&lt;0.0001) was also produced by the extract in comparison with the control. This effect however was not dose dependent. The results suggest that the plant has significant peripheral and central analgesic effects, which may not be dependent on dose. Inhibition of the synthesis of prostaglandins may account for its peripheral analgesic effect, while its action on central receptors may account for its central analgesic activities.

Synthesis and evaluation of analgesic, anti-inflammatory, and anticancer activities of new pyrazole-3(5)-carboxylic acid derivatives

In this article, we synthesized a series of novel 1-benzyl-5(3)-p-tolyl-1H-pyrazole-3(5)-carboxylic acid derivatives and characterized by IR, 1H NMR, and mass spectroscopy. Compounds were evaluated for their in vivo analgesic and anti-inflammatory activity using the p-benzoquinone-induced writhing test and the carrageenan-induced paw edema model, respectively. Out of 14 compounds tested, 7a, 7c, 7e, 7f, 7i, 8a–b, and 8f–g exhibited potent analgesic and/or anti-inflammatory activity as compared to reference drugs aspirin and indomethacin. Anticancer activity of these compounds was assessed against five cancer cell lines with the MTT assay (HL-60, human promyelocytic leukemia cells; HeLa, human cervical cancer cells; Raji, human B lymphocyte cell line; MCF7, human breast adenocarcinoma cell line; MDA-MB-231, estrogen-independent human breast cancer cell line). Compounds 7a, 8a, and 8b with high anti-inflammatory activity, and also 7d and 7j with mild anti-inflammatory activity exhibited promising anticancer activity against some selected cell lines.

Synthesis, analgesic, anti-inflammatory and ulcerogenic properties of some novel N'-((1-(substituted amino)methyl)-2-oxoindolin-3-ylidene)-4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl)benzohydrazide derivatives

A new series of N'-((1-(substituted amino)methyl)-2-oxoindolin-3-ylidene)-4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl)benzohydrazide derivatives 4a-4l were designed and synthesized from anthranilic acid. All the synthesized compounds were characterized by spectroscopic means and elemental analyses. The tail-flick technique and the carrageenan-induced foot paw edema test were performed for screening analgesic and anti-inflammatory activity, respectively. All of the compounds were also examined for their ulcerogenicity. Some of the compounds showed significant activity. Among the test compounds, 4b exhibited 53% and 69% analgesic activity at a dose of 10 and 20 mg/kg, respectively. It also displayed 47% (10 mg/kg) and 65% (20 mg/kg) anti-inflammatory activity with one-fourth of ulcer index of the reference drugs diclofenac and aspirin.

Synthesis and in vitro activities on anti-platelet aggregation of N,N′-di(2-substituted-phenyl)-4-methoxy isophthalamides and benzene-1,3-disulfonamides

Abstract On the propose of searching for the SAR and obtaining novel antiplatelet aggregating drugs, we have described the synthesis procedure and the activities in vitro on antiplatelet aggregation of two series of derivatives, which contain both 18 N , N ′-di(2-substitutedphenyl)-4-methoxyisophthalamides ( 2a – 2r ) of the 2 series and nine N , N ′-di(2-substitutedphenyl)-4-methoxybenzene-1,3-disulfonamides ( 3a – 3i ) of the 3 series. The results showed that three compounds 2e , 2i and 3g emerged as significant activities of antiplatelet aggregation, superior to two reference drugs picotamide and aspirin, and eight compounds 2j , 2k , 2l , 2o , 2p , 2q , 2r and 3i merely superior to picotamide. The preliminary SAR shows that it is favorable for the 2 series to increase the activities via the steric hindrance substituents attached to the two side chain benzene rings at 2-positions. And the arylamides of the 2 series have better the activity values than the arylsulfonamides of the 3 series respective except for 3b and 3g . On the contrary, electrostatic factors would not contribute evidently to the activities of the two series. The structures of 15 compounds newly synthesized have been established by MS and 1 H NMR and been first reported in this paper.

Synthesis and Anti‐inflammatory Activity of 1‐Benzyl‐2‐(X‐thio)pyrrolo[2, 3‐d]imidazole‐5‐carboxylates

A series of 1-benzyl-2-(X-thio)pyrrolo[2, 3-d]imidazole-5-carboxylates, were synthesized and tested as anti-inflammatory agents. Indomethacin and aspirin were used as reference drugs. All compounds except 6d had almost the same activity against carrageenan-induced oedema in the hindpaws of rats. Our results show that compounds 6a-c were almost 1·5 times more active than the reference drug aspirin. In addition, they had one-seventh the activity of indomethacin.

Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Synthesis, biological evaluation and nitric oxide release studies

A new class of anti-inflammatory (AI) cupferron prodrugs was synthesized wherein a diazen-1-ium-1,2-diolato ammonium salt, and its O2-methyl and O2-acetoxyethyl derivatives, nitric oxide (NO) donor moieties were attached directly to an aryl carbon on a celecoxib template. The percentage of NO released from the O2-methyl and O2-acetoxyethyl compounds was higher (18.0–37.8% of the theoretical maximal release of one molecule of NO/molecule of the parent compound) upon incubation in the presence of rat serum, relative to incubation with phosphate buffer saline (PBS) at pH 7.4 (3.8–11.6% range). All compounds exhibited weak inhibition of the COX-1 isozyme (IC50=5.8–17.0μM range) in conjunction with weak or modest inhibition of the COX-2 isozyme (IC50=1.6–14.4μM range). The most potent AI agent 5-[4-(O2-ammonium diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole exhibited a potency that was about fourfold and twofold greater than that observed for the respective reference drugs aspirin and ibuprofen. These studies indicate that use of a cupferron template constitutes a plausible drug design approach targeted toward the development of AI drugs that do not cause gastric irritation, or elevate blood pressure and induce platelet aggregation that have been associated with the use of some selective COX-2 inhibitors.