Reaction of phthalimido alkyl acids with isopropylamine: synthesis, anti-inflammatory and antinociceptive properties

Phthalimido alkyl acids 3-phthalimidopropionic acid (2a) and 4-phthalimidobutyric acid (2b) were treated with isopropylamine at room temperature using different solvents (dimethylformamide, dichloromethane and methanol) as the reaction medium and afforded 3-benzamido-propionic acid –2-(2- methylethyl)-carboxamide (3), 2-benzamido-2-methylethane-2-(2-methylethyl)-carboxamide (4), and 4- benzamido-butyric acid –2-(2-methylethyl)- carboxamide (5). Compound 4 was a dimmer that was least expected. Compounds 3, 4 and 5 were evaluated for antinociceptive property using acetic acid-induced writhing test. 4 exhibited the highest analgesic effect at 80 mg/kg it caused 88 % inhibition and was more pronounced than the reference drugs (indomethacin, acetylsalicylic acid and paracetamol), 3 and 5. The anti-inflammatory activity of the compounds was also screened using carrageenan- induced rat paw oedema assay and 4 showed higher activity than others except the reference drug. The effects were dose-dependent.Key words: Phthalimido alkyl acids, mice, antinociception, mouse writhing test, isopropylamine, antiinflammatory activity

Antioxidant activity of compounds isolated from the butanol fraction of Acalypha wilkesiana var. golden-yellow (Muell & Arg.)

Background: Free radicals (FR) and other reactive oxygen species (ROS) are major sources of concern in some health conditions such as wounds, ulcers, inflammations, heart troubles and cancers amongst many others. These chemical species have been implicated as the causative agents of these and many more similar disease conditions. The cost of treating / managing these medical conditions has continued to take a huge toll on the socio-economic status of sufferers/patients. Many bio-resources such as plants are now being used to mitigate this worrisome health challenge. Objective: To investigate the antioxidant activity of Acalypha wilkesiana var. golden-yellow (Muell & Arg.) syn. A. wilkesiana var. tropical tempest. Methods: The leaf crude extract, butanol fraction and three isolates (W-1, W-2 and W-3 previously obtained from the silica-gel column chromatographic separation of the butanol fraction) were to be screened for antioxidant activities using the rapid free-radical scavenging activity test and absorption spectrophotometry, both employing DPPH reagent. Results: The initial free-radical scavenging activity of the plant was confirmed when the DPPH reagent-sprayed spots of the plant extract/fraction/isolates (W-1, W-2 and W-3) showed white color on purple background. W-1 (an ester) gave a marginal IC50 of 0.77 μg mL-1as vitamin A at 0.79 μg mL-1 while W-2 (a diol) and W-3 (phenol) both demonstrated moderate antioxidant activities of 0.58 and 0.53 μg mL-1 respectively. However, W-3 was more antioxidant in its action and its value compare favorably with IC50 value obtained with vitamin C (a standard antioxidant drug) at 0.41μg mL-1. Conclusion: The results of the antioxidant assays have showed that the compounds obtained from the plant (especially W-2 and W-3) could be considered as lead antioxidant drug templates in further in-vitro [especially structural activity relationship studies (SARS)] and in-vivo studies with the aim of improving on their activities. Keywords: Free- radicals; antioxidant activity; DPPH assay; isolates; Acalypha wilkesiana var.golden-yello

Adsorptive property of kaolin in some drug formulations

Purpose: Kaolin is a known adsorbent, has lubricant property in powders and is therefore proposed as a lubricant in tablet formulations. This study was carried out to evaluate whether kaolin can adsorb some active drugs when mixed with them in tablet formulations even at very low concentrations. Method: Chloroquine and chlorpheniramine tablets were formulated with powder mixtures containing various concentrations of kaolin. The effect of kaolin on the physical properties of the tablets were examined and compared with those of standard lubricants like magnesium stearate and talc. Chloroquine and chlorpheniramine tablets and powders of amoxicillin/clavulanic acid oral powder and ampicillin/cloxacillin injection were also mixed with and without various concentrations of kaolin in water. Chemical assay of the drugs in the solutions were determined over time. Results: Kaolin significantly reduced the amount of each of the drugs in the solutions containing kaolin. Conclusion: Kaolin reduces the amount of some drugs when incorporated in drug formulations. Therefore, its inclusion in such drug formulations should not be encouraged. Keywords: Adsorption, ampicillin/cloxacillin, amoxicillin/clavulanic acid, chloroquine, chlorpheniramine, drug formulation, kaolin. Tropical Journal of Pharmaceutical Research 2003; 2(1): 155-15

Association between culture and the preference for, and perceptions of, 11 routes of medicine administration: A survey in 21 countries and regions

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected. A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart–Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected. A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one

Reaction of phthalimido alkyl acids with isopropylamine: synthesis, anti-inflammatory and antinociceptive properties

Phthalimido alkyl acids 3-phthalimidopropionic acid (2a) and 4-phthalimidobutyric acid (2b) were treated with isopropylamine at room temperature using different solvents (dimethylformamide, dichloromethane and methanol) as the reaction medium and afforded 3-benzamido-propionic acid –2-(2methylethyl)-carboxamide (3), 2-benzamido-2-methylethane-2-(2-methylethyl)-carboxamide (4), and 4benzamido-butyric acid –2-(2-methylethyl)-carboxamide (5). Compound 4 was a dimmer that was least expected. Compounds 3, 4 and 5 were evaluated for antinociceptive property using acetic acid-induced writhing test. 4 exhibited the highest analgesic effect at 80 mg/kg it caused 88 % inhibition and was more pronounced than the reference drugs (indomethacin, acetylsalicylic acid and paracetamol), 3 and 5. The anti-inflammatory activity of the compounds was also screened using carrageenan-induced rat paw oedema assay and 4 showed higher activity than others except the reference drug. The effects were dose-dependent

Anti-inflammatory Activity of Cyathula prostrata (L.) Blume

Background: Cyathula prostrata (L.) Blume which belongs to the Amarantheceae family is used in traditional medicine for the treatment of chest troubles, dysentery, diarrhea, skin ulcers, scabies, sexually transmitted diseases (STDs), tumours and inflammations amongst many others. The growing concerns associated with the incidence of reactive free-radicals widely implicated in many health conditions prompted this present study. Objectives: The crude extract, fractions and two previosly isolated compounds (HOO-1and HOO-2) from the plant were to be screened for anti-inflammatory activities with the aim of confirming or disproving its uses such as wound healing, treating skin ulcers and rheumatism amongst many others. Methodology: The xylene and chorio-allantoic membrane (CAM) models were employed in the determination of  the anti-inflammatory activity of  the plant. Results and Discussion: The xylene-model test for anti-inflammatory activity showed that the ethyl-acetate fraction and HOO-2 gave moderately similar anti-inflammatory activity of 53.48 % while HOO-1was comparably less active at 30.20 %. The chorio-allantoic membrane (CAM) model also indicated that both the ethyl-acetate fraction and HOO-2 gave moderate anti-inflammatory activity of 52.00 % while HOO-1 was less active at 44.00 %. However, the other fractions were weakly active. These results obtained from this study were not surprising because the phytochemical screening of the extract indicated the presence of flavonoids and terpenes which have demonstrated anti-inflammatory activities in previous studies. Furthermore, the results show some consistency irrespective of the model used. Conclusion: The results obtained in this study have lent scientific justification to the folklore uses of the plant in treating and managing inflammatory conditions. Keywords: anti-inflammatory; xylene-model; chorio-allantoic membrane (CAM); Cyathula prostrat

One-pot synthesis of N-benzyl-2-aminobenzoic acid, via ring opening of isatoic anhydride derivative, and its antibacterial screening

2-(N-Benzyl) amino benzoic acid is a bifunctional molecule that could be produced from the reaction between isatoic anhydride and aryl halide. Analogues and derivatives of isatoic anhydride have wide application in pharmaceuticalsincluding antibacterial activity. The aim of this study is to synthesize, characterize and screen N-benzyl isatoic anhydride and 2-(N-benzyl) amino benzoic acid for antibacterial activity. The reaction of isatoic anhydride and benzyl bromide in the presence of potassium carbonate in DMSO at room temperature yielded N-benzyl isatoic anhydride, which under hydrolysis yielded 2-(N-benzyl) amino benzoic acid in which the anhydride ring is opened up. This compound was screened against Gram positive and negative bacteria. Moderate yield of 2-(N-benzyl) amino benzoic acid, a yellow crystal (melting point of 160-162oC, percentage yield 65 %, Rf 0.19) formed by ring opening of N-benzyl isatoic anhydride. The compound showed no antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas pyocyanea, Salmonella typhimurium, Klebsiella aeruginosa and Bacillus subtilis. 2-(N-benzyl)amino benzoic was synthesized, characterized and showed no activity against bacteria

O OR RI IG GI IN NA AL L A AR RT TI IC CL LE E Novel Anti-oxidant Activity of Cyathula prostrata (L.) Blume

ABSTRACT Cyathula prostrata is a herbal recipe used in traditional medicine for the treatment of chest . Though, its use in the treatment and management of inflammatory conditions is well known but there is yet any claim on its use as an antioxidant agent. Hence, the tests for free-radical scavenging (antioxidant) activity were considered relevant