Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (v.13, #2)

Efficacy and Safety of Inhaled and Intranasal Corticosteroids by Akefeh Ahmadiafshar, Sahar Ahmadiafshar (83-87).
Inflammation is an important phenomenon in allergic disorders and corticosteroid drugs since their anti inflammatoryproperties have a pivotal role in improvement, control and relieving the symptoms and signs of asthma, allergicrhinitis, atopic dermatitis and many other inflammatory disorders. Nevertheless, the prescription of these drugs mightbe associated with some unwanted reactions such as hyperglycemia, hypertension, Cushing's syndrome, adrenal insufficiencyand growth failure. In recent decades administration of intranasal and inhaled corticosteroids instead of systemicparenteral or oral drugs reduced some of these concerns during treatment of patients and enable them to receive the effectiveand safer kind of therapy in acute or chronic inflammatory disorders of nose and airways. In this article the propertiesof inhaler (ICS) and intranasal corticosteroids (INCS) were reviewed.

Studies on Growth Kinetics of Serratia marcescens VITSD2 and Optimization of Fermentation Conditions for Serratiopeptidase Production by C. Subathra Devi, Shah Alam, Suraj Kumar Nag, S. Jemimah Naine, V. Mohanasrinivasan, B. Vaishnavi (88-92).
Serratia is one of the most important groups of bacteria which produces proteolytic enzymes effectively andknown to possess anti- inflammatory properties. The main focus of the current study was to optimize the culture conditionsof Serratia marcescens VITSD2 for the mass production of serratiopeptidase. Effect of various nutritional and environmentalfactors were analysed and optimized. Among the different carbon and nitrogen sources tested, mannose andsoya bean meal was found to be the best with enzyme activity of 1391 units /mL and 1800 U/mL respectively. The enzymeshowed an optimum activity of 1668 U/mL at pH-8 and 1500 U/mL at 25°C. Maximum peptidase production duringfermentation was obtained after 24 h incubation with 1% inoculum in the medium at 25°C and yielded 1668 U/mL. Lysinestimulated the production of peptidase and the yield obtained was 2410U/mL. Growth curve analysis was done. Maximumserratiopeptidase 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 maximumby varying the cultural conditions.

Benefits of Oral and Topical Administration of ROQUETTE Chlorella sp. on Skin Inflammation and Wound Healing in Mice by Sophie Hidalgo-Lucas, Jean-Francois Bisson, Anais Duffaud, Amine Nejdi, Laetitia Guerin-Deremaux, Blandine Baert, Marie-Helene Saniez-Degrave, Pascale Rozan (93-102).
The human body is constantly exposed to the risk of traumatic lesions. Chlorella is a green microalgae enrichedwith nutrients, vitamins, minerals and chlorophyll. In some communities, Chlorella is a traditional medicinal plant usedfor 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 dermatologicaldisorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-Otetradecanoylphorbol13-acetate (TPA). For wound healing the microalgae was administered by topical application afterscarification of the skin until complete wound healing. Results indicated that oral and topical administrations of the twohigher doses of RCs had significant effects on macroscopic score of skin inflammation with an efficient effect on microscopicscore with cutaneous application. The microalgae had also efficient effect on healing process and duration ofwound healing for both administration routes and particularly at the two highest doses of RCs. These findings suggest thatadministration of RCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

The Effect of the Antioxidant Drug "U-74389G" on Oophoritis During Ischemia Reperfusion Injury in Rats by Constantinos |sompos, Constantinos Panoulis, Konstantinos ||utouzas, George |ografos, Apostolos Papalois (103-107).
The aim of this experiment was to study the effects of the antioxidant drug “U-74389G” on rat model, particularlyin ischemia reperfusion protocol. The beneficial or other effects of that molecule were studied estimating the meanoophoritis (OI) lesions. Materials and methods: 40 rats were used of mean weight 231.875 g. OI was evaluated 60 min afterreperfusion for groups A and C and 120 min after reperfusion for groups B and D. Groups A and B were without thedrug but C and D with U-74389G administration. Results were that U-74389G administration kept non-significantly increasedthe OI scores by 0.05±0.051 without lesions (p=0.3204). Reperfusion time kept non-significantly increased the OIscores by 0.05±0.051 also without lesions (p=0.3204). Nevertheless, U-74389G administration and reperfusion time togetherkept non-significantly increased the OI scores by 0.045±0.030 (p=0.1334). Conclusions: Results of this study indicatethat U-74389G administration, reperfusion time and their interaction declined the increased OI scores from significantto non-significant level.

There are contradictory reports about the association of cytokines levels and major depressive disorder and thepossible therapeutic role of aspirin for treating major depressive disorder (MDD). A clinical sample of adult out-patientswith MDD was recruited. At recruitment, they were interviewed face to face according to DSM-IV diagnostic criteria. Inaddition, Hamilton depression rating scale was completed by a psychiatrist. The patients were invited to receive aspirin orplacebo. All the 10 patients received 160mg/day aspirin plus citlaopram 20 mg/day. Eight out of ten patients showed severeanxiety and akathesia from early days of this trial. Except for two patients, we discontinued the medication during 14days of this trial. Three patients were hospitalized due to anxiety and akathesia. Two patients reported suicidal behaviorafter the onset of this trial. This trial of aspirin adjuvant therapy for treating MDD suggests that this combination is notsafe and there are some serious and intolerable adverse effects. This finding is in contrast to the suggestions assuming thataspirin may be effective for treating MDD. Aspirin may negatively impact on both pro- and anti-inflammatory cytokinesbalance in depression. Aspirin may antagonize the antidepressant effect of citalopram.

Synthesis, Characterization and Anti-inflammatory Activity of N-(4- phenyl-1, 3-thiazol-2-yl)-N'-phenylureas by Aneesa Fatima, Ravindra Kulkarni, Bhagavanraju Mantripagada, Asief Mohammed, Anusaya Birajdar, V.M. Chandrasheskar (112-120).
A series of N-(4-phenyl-1, 3-thiazol-2-yl)-N'- phenylureas (5a-z) was synthesized from 2-amino-4-substitutedphenylthiazoles and phenylisocyanates. The newly synthesized compounds were characterized by IR, 1H NMR and Massspectral data. All the twenty six N-(4-phenyl-1, 3-thiazol-2-yl)-N'-phenylurea derivatives were screened for antiinflammatoryactivity 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 thetraditional 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 systemicenvironment. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the biosynthesis of PGE2, which can lead to globalPGE2 deficiency, resulting in serious side effects in the gastrointestinal, renal and other systems. In contrast, various pyridinederivatives 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, pyridinolcarbamate, 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 controlsfrom previously published, independent studies. Results: Overall, in all our investigations P values for unpaired orpair-wise comparisons were not statistically significant. Conclusions: We demonstrated that using pyridine derivativesalong with NSAIDs, such as nonselective cyclooxygenase (COX) and selective COX-2 inhibitors, does not reduce endogenousPGE2 expression to below basal levels. This finding is based on both in vitro studies using animal and humantissues and in vivo studies performed with healthy volunteers. Using pyridine derivatives to correct a PGE2 deficiency duringNSAID treatment is a novel method that we propose can offer a valuable, cost-effective therapeutic approach to preventingand treating the side effects of NSAIDs.

Synthesis of Some New Flurbiprofen Analogues as Anti-inflammatory Agents by Laxmikant H. Nitlikar, Jaiprakash N. Sangshetti, Devanand B. Shinde (128-138).
A series of new ?-aryl propionic acid derivatives had been synthesized through different synthetic routes fromthe readily available 2-fluoronitrobenzene as key starter.The synthesized compounds were screened for their antiinflammatoryactivity using rat paw edema method. Azoles (6c, 6h and 6i) have showed considerable good antiinflammatoryactivity. The present series with some modification may serve as important core for the development of newanti-inflammatory agents.