Ionic liquid-assisted synthesis of celexocib using tris-[2-hydroxyethyl] ammonium acetate as an efficient and reusable catalyst

Celecoxib is classified as none traditional nonsteroidal anti-inflammatory drugs [NSAIDs]. This compound has conventional properties of NSAIDs such as anti-inflammatory, analgesic, and antipyretic activities beside reduced risk of gastrointestinal side effect of traditional NSAIDs such as ibuprofen. This compound gets a second sale rank of NSAIDs market at 2016 in the world and sales more than 17000 Kg in Iran during the past 6 month. So, a simple, rapid and green method for synthesis of this compound is important. In the present study, a novel green method was suggested for the synthesis of celecoxib using the ionic liquid. Celecoxib was provided by the reaction of trifluoroacetone, 4-methylbenzoylchloride, and 4-hydrazinobenzenesulfonamide hydrochloride. The tris-[2-hydroxyethyl] ammonium acetate as ionic liquid was prepared by mixing tris-[2-hydroxyethyl] ammonium and acetic acid, and used as an efficient catalyst. The structure of the synthetic products was confirmed by analytical and spectroscopic methods including 1HNMR, [13]CNMR, IR, MS and elemental analysis. This ionic liquid can play dual roles in the synthesis of celecoxib, as a catalyst to improve electrophilicity of carbonyl group and also as a solvent of reaction. The reaction rate and yield [86%] were improved considerably. Moreover IL showed the same efficiency when used in 4 consecutive reactions

Synthesis and antiplatelet aggregation activity evaluation of some 2-aminopyrimidine and 2-substituted-4,6-diaminopyrimidine derivatives

A series of novel 2-aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma using light transmission aggregometry. Among the tested derivatives, compounds Ia, I[b], I[B] and II[16] exhibited the highest antiplatelet aggregation activity [36.75, 72.4, 62.5 and 80 microM]. None of the compounds showed satisfactory activity against the aggregation induced by ADP but acceptable activities were observed against the aggregation induced by arachidonic acid. 2- aminopyrimidines were more active than 4,6- diaminopyrimidines in this respect

Intracellular GSH alterations and its relationship to level of resistance following exposure to cisplatin in cancer cells

One of the major complications in cancer chemotherapy with cisplatin as one of the important medicines in treatment regimens of different cancers is the development of resistance. One of the most described cellular defense mechanisms involved in resistance is glutathione [GSH], thus in this study, the effects of cisplatin on the total intracellular GSH level [GSHi] in some sensitive and resistant variants of human cell lines [hepatocarcinoma HepG2, sking A375, cisplatin sensitive glioblastoma U373MG and cisplatin resistant glioblastoma U373MGCP, cisplatin sensitive ovary A2780S and cisplatin resistant A2780CP cells] were studied. MTT assay was performed to measure cytotoxicity of cisplatin [33.3 microM for 1 hour]. Following cisplatin exposure, GSHi [per million cells] was evaluated using a photometrical assay up to 90 minutes. Our results indicate that there are significant differences between GSHi content of A2780CP and U373MGCP cells compared to other cell lines. Moreover, IC[50] of cisplatin in different cells seems to have a relation with mean of GSH level in 90 minutes [GSH [mean][90]]. As a conclusion, it seems that resistance to cisplatin in different cell lines is more related with the diverse patterns of GSHi variations following cisplatin exposure than its original level, and/or its cellular increase or decrease. It is also suggested that GSH [mean][90] may be used as a factor for the prediction of cellular resistance to cisplatin

Synthesis and evaluation of new fluorinated anti-tubercular compounds

Treatment of tuberculosis [TB] and the discovery of effective new anti tubercular drugs is one of the most urgent priorities in health organizations all around the world. In the present study, fluorinated analogs of some of the most important anti-TB agents such as p-aminosalicylic acid [PAS], thiacetazone and pyrazinamide were synthesized and tested against TB. The fluorinated analog of thiacetazone was 20 times more potent than the parent compound against M.tuberculosis H37-RV, while the fluorinated PAS was almost three times less potent than PAS. A few other halogenated analogs of thioacetazone were also synthesized and subjected to anti-TB screening tests. The best halogen substituent was found to be fluorine which has the smallest size from one hand and the strongest electronegativity from the other hand among the halogen atoms. This fact reemphasizes the unique nature of fluorine as a golden substituent in medicinal chemistry

Synthesis of N-arylmethyl substituted indole derivatives as new antiplatelet aggregation agents

A number of N-arylmethyl substituted indole derivatives have been synthesized and their effectiveness against ADP and arachidonic acid induced platelet aggregation in human plasma was determined. The desired compounds were synthesized by reacting the appropriate aniline derivative with isatin [or substituted isatin] to form the corresponding imine structures. The so formed compound was then activated using sodium hydride and reacted with the proper substituted benzyl halides. Among the tested compounds, derivatives 4a, 4c, 4d, 4f-i and 4k were the most potent compounds with satisfactory IC[50] values [under 38.5 micro M] for inhibition of platelet aggregation induced by arachidonic acid. All indole derivatives without substitution on position 1 of the indole ring, exhibited either weaker activities or were not active at all

Electrochemical synthesis of novel 1, 3-indandione derivatives and evaluation of their antiplatelet aggregation activities

Electrochemical oxidation of some selected catechol derivatives, using cyclic voltammetry, in the presence of different 2-aryl-1, 3-indandiones as nucleophiles, resulted in electrochemical synthesis of new 1, 3- indandione derivatives in an undivided cell in good yield and purity. A Michael addition mechanism was proposed for the formation of the analogs based on the reaction conditions which were provided in electrochemical cell. The in-vitro antiplatelet and anticoagulant activity of these compounds was evaluated, using arachidonic acid [AA] and adenosine diphosphate [ADP] as the platelet aggregation inducers. The results show that the incorporation of catechol ring in 1, 3-indandione nucleus leads to the emergence of antiplatelet aggregation activity in these compounds. The compounds may exert their antiaggregation activity by interfering with the arachidonic acid pathway

simple electrochemical method for the rapid estimation of antioxidant potentials of some selected medicinal plants

Clinical and Epidemiological studies have shown that a diet rich in fruits and vegetables is associated with a decreased risk of cardiovascular diseases, cancers and other related disorders. These beneficial health effects have been attributed in part to the presence of antioxidants in dietary plants. Therefore screening for antioxidant properties of plant extracts has been one of the interests of scientists in this field. Different screening methods have been reported for the evaluation of antioxidant properties of plant extracts in the literature. In the present research a rapid screening method has been introduced based on cyclic voltammetry for antioxidant screening of some selected medicinal plant extracts. Cyclic Voltammetry of methanolic extracts of seven medicinal plants: Buxus hyrcana, Rumex crispus, Achillea millefolium, Zataria multiflora, Ginkgo biloba, Lippia citriodora and Heptaptera anisoptera was carried out at different scan rates. Based on the interpretation of voltammograms, Rumex crispus, Achillea millefolium and Ginkgo biloba showed higher antioxidant capability than the others while Lippia citriodora contained the highest amount of antioxidants. Cyclic voltammetry is expected to be a simple method for screening antioxidants and estimating the antioxidant activity of foods and medicinal plants