Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry - Volume 13, Issue 2, 2014

Inflammation is an important phenomenon in allergic disorders and corticosteroid drugs since their anti inflammatory properties have a pivotal role in improvement, control and relieving the symptoms and signs of asthma, allergic rhinitis, atopic dermatitis and many other inflammatory disorders. Nevertheless, the prescription of these drugs might be associated with some unwanted reactions such as hyperglycemia, hypertension, Cushing's syndrome, adrenal insufficiency and growth failure. In recent decades administration of intranasal and inhaled corticosteroids instead of systemic parenteral or oral drugs reduced some of these concerns during treatment of patients and enable them to receive the effective and safer kind of therapy in acute or chronic inflammatory disorders of nose and airways. In this article the properties of inhaler (ICS) and intranasal corticosteroids (INCS) were reviewed.

Serratia is one of the most important groups of bacteria which produces proteolytic enzymes effectively and known to possess anti- inflammatory properties. The main focus of the current study was to optimize the culture conditions of Serratia marcescens VITSD2 for the mass production of serratiopeptidase. Effect of various nutritional and environmental factors were analysed and optimized. Among the different carbon and nitrogen sources tested, mannose and soya bean meal was found to be the best with enzyme activity of 1391 units /mL and 1800 U/mL respectively. The enzyme showed an optimum activity of 1668 U/mL at pH-8 and 1500 U/mL at 25ºC. Maximum peptidase production during fermentation was obtained after 24 h incubation with 1% inoculum in the medium at 25ºC and yielded 1668 U/mL. Lysine stimulated the production of peptidase and the yield obtained was 2410U/mL. Growth curve analysis was done. Maximum serratiopeptidase production was detected after 24 h incubation with 2155 units/mL and cell density of 2.4g/100mL. Hence the observation of the present study clearly indicates that the yield of Serratiopeptidase was found to be maximum by varying the cultural conditions.

The human body is constantly exposed to the risk of traumatic lesions. Chlorella is a green microalgae enriched with nutrients, vitamins, minerals and chlorophyll. In some communities, Chlorella is a traditional medicinal plant used for the management of inflammation-related diseases. ROQUETTE Chlorella sp. (RCs) was investigated by oral administration (125, 250 and 500 mg/kg) and cutaneous application (2.5, 5.0 and 10.0%) to evaluate its impact in two dermatological disorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during 14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-Otetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered by topical application after scarification of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of RCs had significant effects on macroscopic score of skin inflammation with an efficient effect on microscopic score with cutaneous application. The microalgae had also efficient effect on healing process and duration of wound healing for both administration routes and particularly at the two highest doses of RCs. These findings suggest that administration of RCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

The aim of this experiment was to study the effects of the antioxidant drug “U-74389G” on rat model, particularly in ischemia reperfusion protocol. The beneficial or other effects of that molecule were studied estimating the mean oophoritis (OI) lesions. Materials and methods: 40 rats were used of mean weight 231.875 g. OI was evaluated 60 min after reperfusion for groups A and C and 120 min after reperfusion for groups B and D. Groups A and B were without the drug but C and D with U-74389G administration. Results were that U-74389G administration kept non-significantly increased the OI scores by 0.05±0.051 without lesions (p=0.3204). Reperfusion time kept non-significantly increased the OI scores by 0.05±0.051 also without lesions (p=0.3204). Nevertheless, U-74389G administration and reperfusion time together kept non-significantly increased the OI scores by 0.045±0.030 (p=0.1334). Conclusions: Results of this study indicate that U-74389G administration, reperfusion time and their interaction declined the increased OI scores from significant to non-significant level.

There are contradictory reports about the association of cytokines levels and major depressive disorder and the possible therapeutic role of aspirin for treating major depressive disorder (MDD). A clinical sample of adult out-patients with MDD was recruited. At recruitment, they were interviewed face to face according to DSM-IV diagnostic criteria. In addition, Hamilton depression rating scale was completed by a psychiatrist. The patients were invited to receive aspirin or placebo. All the 10 patients received 160mg/day aspirin plus citlaopram 20 mg/day. Eight out of ten patients showed severe anxiety and akathesia from early days of this trial. Except for two patients, we discontinued the medication during 14 days of this trial. Three patients were hospitalized due to anxiety and akathesia. Two patients reported suicidal behavior after the onset of this trial. This trial of aspirin adjuvant therapy for treating MDD suggests that this combination is not safe and there are some serious and intolerable adverse effects. This finding is in contrast to the suggestions assuming that aspirin may be effective for treating MDD. Aspirin may negatively impact on both pro- and anti-inflammatory cytokines balance in depression. Aspirin may antagonize the antidepressant effect of citalopram.

A series of N-(4-phenyl-1, 3-thiazol-2-yl)-N'- phenylureas (5a-z) was synthesized from 2-amino-4-substituted phenylthiazoles and phenylisocyanates. The newly synthesized compounds were characterized by IR, 1H NMR and Mass spectral data. All the twenty six N-(4-phenyl-1, 3-thiazol-2-yl)-N'-phenylurea derivatives were screened for antiinflammatory activity by following carrageenan induced rat paw edema method. Among the compounds screened, N-[4- (4-methoxy phenyl)-1, 3-thiazol-2-yl)-N'-phenylurea and N-[4-(4-methoxy phenyl-1, 3-thiazol-2-yl)-N'-(4-bromophenyl) urea were found to be more potent. The molecular docking interaction of aforementioned urea compounds revealed the traditional type II p38 kinase inhibitor’s interactions in the DFG out active site.

Background: Prostaglandin E2 (PGE2) plays key physiological roles within the body’s organs and the systemic environment. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the biosynthesis of PGE2, which can lead to global PGE2 deficiency, resulting in serious side effects in the gastrointestinal, renal and other systems. In contrast, various pyridine derivatives have been found to increase endogenous PGE2 levels within multiple organs and the systemic environment. We hypothesised that the use of pyridine derivatives (nicotinic acid, nicotine, niceritrol, nicotinyl alcohol, pyridinol carbamate, pyridoxine hydrochloride and pyridostigmine bromide) can recover PGE2 levels during NSAID treatment. Methods: Reassessment of experimental data on PGE2 levels in NSAIDs and pyridine derivatives treatment, and in controls from previously published, independent studies. Results: Overall, in all our investigations P values for unpaired or pair-wise comparisons were not statistically significant. Conclusions: We demonstrated that using pyridine derivatives along with NSAIDs, such as nonselective cyclooxygenase (COX) and selective COX-2 inhibitors, does not reduce endogenous PGE2 expression to below basal levels. This finding is based on both in vitro studies using animal and human tissues and in vivo studies performed with healthy volunteers. Using pyridine derivatives to correct a PGE2 deficiency during NSAID treatment is a novel method that we propose can offer a valuable, cost-effective therapeutic approach to preventing and treating the side effects of NSAIDs.

A series of new α-aryl propionic acid derivatives had been synthesized through different synthetic routes from the readily available 2-fluoronitrobenzene as key starter. The synthesized compounds were screened for their antiinflammatory activity using rat paw edema method. Azoles (6c, 6h and 6i) have showed considerable good antiinflammatory activity. The present series with some modification may serve as important core for the development of new anti-inflammatory agents.