Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 18, Issue 2, 2019

Background: Toxocariasis is a cosmopolitan infection that occurs in various regions worldwide, more frequently in developing countries. Chronic infections with Toxocara species in humans are associated with the production of high levels of specific and non-specific antibodies of all isotypes and IgG subclasses and a cytokine response characterized by the production of Th2 cytokines including IL-4, IL-5 and IL-13 by Peripheral Blood Monocytes (PBMCs) and Leukocytes (PBLs) in whole blood cultures. Other Th2 effector responses are also prominent during infection, reflected by elevated numbers of peripheral blood eosinophils and increased expression of eosinophil degranulation products. The production of IFN-γ by PBMCs/PBLs stimulated with Toxocara-secreted proteins is not prominent in toxocariasis but IL-10 production may be increased in infected individuals. The relationship between Toxocara species with allergic reactions was reported in the recent century. Experimental and epidemiological investigations revealed that toxocariasis with this parasite led to the development of allergic symptoms, such as asthma. However, the findings are conflicting since in other investigations no association between these two immunopathologies has been reported. Conclusion: The present review endeavours to summarize the data on Toxocara species and findings from studies on the relationship of toxocariasis with symptoms and signs of allergy. Furthermore, the mechanisms of immune responses and the factors associated between allergy and Toxocara infection are discussed.

Background: Chemical modification of thiadiazole may lead to a potent therapeutic agent. In this study, biological properties of thiadiazole derivatives were evaluated by assessing their antimicrobial and anti-inflammatory activities. Methods: A series of novel derivatives of N-(5-(1-methyl-indol-3-yl)-1,3,4-thiadiazol-2- yl)-2-(5-substitutedphenyl)-3-(phenylamino)-4,5-dihydropyrazol-1-yl) acetamide have been synthesized and evaluated for their antimicrobial activity. Anti-inflammatory activity was done using carrageenan-induced inflammation in rat paw edema model. In-silico molecular docking studies of the synthesized compounds were performed on crystal structures of Aspergillus niger, Bacillus subtilis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Cyclooxygenase-2 (obtained from www.rcsb.org) using GRIP batch docking method of V-life MDS 3.0 software. The structures of the newly synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy. Results: Antimicrobial and Anti-inflammatory activity study of the novel synthesized compounds were screened. Synthesized compounds having methoxy substitution on the 3rd and 4th positions of aromatic ring are utmost active amongst all the derivatives. Compounds 6d, 6i, 6j and 6l were found to possess good anti-inflammatory activity having percentage of inhibition to the extent of 46.8%, 48.1%, 49.4%, and 48.5% as compared with Diclofenac. Conclusion: The experimental results were further supported by molecular docking analysis describing the better interaction patterns.

Introduction: Nowadays, the group of NSAIDs is used the most widely in order to treat the inflammatory process. But its long-term administration increases the risk of complications of pharmacotherapy. Therefore, today it is urgent to search for new molecules that can selectively block biological targets that directly perceive inflammatory mediators. One of such targets is TRPA1. ZC02-0012, a compound from the group of substituted pyrazinopyrimidinones, which is a selective inhibitor of TRPA1 ion channel. Objective: The aim of our study was to study the anti-inflammatory activity of an innovative molecule under the laboratory code ZC02-0012 from the group of selective inhibitors of TRPA1 ion channel. Materials and Methods: Anti-inflammatory activity of ZC02-0012 was studied on the model of acute exudative inflammation of the paw in response to subplantar injection in the right hind paw of mice with 0.02 ml of 2% formaldehyde solution. The mass of the paw was measured after 4 hours (peak edema) after phlogistic injection. The test substance and the reference drug was administered intragastrically or intramuscularly 45 minutes before the injection of formaldehyde solution. The presence and intensity of antiinflammatory activity was judged by the inhibitory effect, represented in percent. Results and Discussion: Selective inhibitor of the TRPA1 ion channel ZC02-0012 revealed the anti-inflammatory activity at doses of 3 and 9 mg/kg, its intensity is comparable to diclofenac sodium. Conclusion: The selective inhibitor of the ion channel TRPA1, a substance under code ZC02-0012, has an anti-inflammatory activity comparable with diclofenac sodium.

Background: As a marine organism, soft corals can be utilized to be various bioactive substances, especially terpenoids and steroids. The soft corals family which produces bioactive generally come from clavulariidae, alcyoniidae, nephtheidae and xeniidae family. Objective: To investigate the bioactivity of Nitric Oxide (NO) inhibitor release from soft coral crude extracts of Sinularia sp. (SCA), Nephthea sp. (SCB), Sarcophyton sp. (SCC), Sarcophyton sp. (SCD), Sinularia sp. (SCE) and Sinularia sp. (SCF). Materials and Methods: Soft coral is collected from Palu Bay (Central Sulawesi). NO inhibitory release activity measured according to the Griess reaction. Soft corals sample macerated with 1:2 (w/v). Then, Soft coral extracts with the best NO Inhibitor activity partitioned with Dichloromethane, Ethyl acetate, and n-butanol. The bioactive of all crude extracts were identified by GC-MS to find compounds with anti-inflammatory potential. Results: Sarcophyton sp. (SCC) and Sinularia sp. (SCF) are able to inhibit NO concentrations of 0.22 ± 0.04 and 0.20 ± 0.04 μM at 20 mg/mL, respectively. The chemical constituents determined and showed the potential as anti-inflammatory in the crude of Sinularia sp. (SCA) were Octacosane (3.25%). In Nephthea sp., (SCB) were Cyclohexene, 6-ethenyl-6- methyl-1-(1-methylethyl)-3-(1-methylethylidene)-,(S)- (0.55%); Azulene, 1,2,3,4,5,6,7,8- octahydro-1,4-dimethyl-7-(1-methylethylidene)-, (1S-cis)- (0.53%); and 1,7,7-Trimethyl- 2-vinylbicyclo[2.2.1]hept-2-ene (4.72%). In Sarcophyton sp, (SCC) were Eicosane (0.12%); Nonacosane (10.7%); 14(β)-Pregnane (0.87%); Octacosane 6.39%); and Tricosane (1.53%). In Sarcophyton sp. (SCD) were 14(β)-Pregnane (2.69%); and Octadecane (27.43%). In crude of Sinularia sp. (SCE) were Oleic Acid (0.63%); 7,10-Hexadecadienoic acid, methyl ester (0.54%); 14(β)-Pregnane (1.07%); 5,8,11,14-Eicosatetraenoic acid, ethyl ester, (all-Z)- (4.60%); Octacosane (7.75%); and 1,2-Benzisothiazole, 3-(hexahydro-1Hazepin- 1-yl)-, 1,1-dioxide (1.23%). In the crude of Sinularia sp., (SCF) were Oxirane, decyl- (1.38%); Nonacosane (0.57%); Cyclohexanol, 5-methyl-2-(1-methylethenyl)- (0.61%); 14B-Pregnane (0.76%); and Tetratriacontane (1.02%). Conclusion: The extract of Sarcophyton sp. (SCC) and Sinularia sp. (SCF) showed the best NO inhibitory release activity. This study is making soft corals from Central Sulawesi, Indonesia can become a potential organism in the discovery and development of bioactive substances anti-inflammatory.

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune multisystem inflammatory condition that causes microvascular inflammation with the production of various auto-antibodies that play a major role in its pathogenesis. SLE can affect both sexes, all ages, and all ethnic groups with widespread geographical and socioeconomic backgrounds. Asia encompasses people of many sociocultural backgrounds with diverse ethnic. Objective: Due to a lack of national epidemiological research, the incidence and prevalence of SLE in Middle Eastern and Arab countries, have only recently been studied. This article aims to explore the status of SLE in Oman and to record symptoms and signs of SLE at first presentation. Methodology: Medical records of all patients diagnosed with SLE at the Royal Hospital from 2006 to 2014 were reviewed for information recorded at first visit. SLE diagnosis was based on the American College of Rheumatology classification criteria; ACR97 (which includes the clinical manifestation and laboratory evidence). Patients with SLE disease manifestations extrapolated and analyzed. There were 966 patients diagnosed with SLE during the period from 2006 to 2014. Mean (SD) age at presentations was 35.5 (11.5) years. Majority of patients were female which constitutes 88.7% of the total SLE patients with mean age 27.6 (1.4) years. Results: Constitutional symptoms were found in 48.68 of SLE population including fatigue in 35.22%, and weight changes in 13.43%. The cutaneous manifestations that were present included malar rash 37.69%, photosensitivity 35.10%, discoid lupus 17.63%, and hair loss 39.29%. Musculoskeletal manifestations were commonly seen among the studied population including arthralgia in 68.75%, myalgia in 55.65%, arthritis in 48.31%, whilst myositis, tendon abnormalities and avascular necrosis were found in only 2.47%, 0.31% and 1.98%. respectively. Conclusion: This is the first study of the symptoms and signs at initial clinical presentation of SLE patients compared to other studies done regionally where most have focused on clinical manifestations during the progression course of SLE. SLE manifestations may be related to the differences in the genetic make-up of the patients who come from various ethnic groups despite similar geography or sociocultural background, or to referral bias, as some studies were performed in the nephrology units and others in the rheumatology units. There is a pressing need to establish a nationwide and regional collaboration to establish LUPUS and to put forward a strategic planning with each MOH to provide an easy and efficient report of SLE cases and provide various effective management for such a debilitating syndrome.

Objective: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is reported in the literature ranging from 1 to 14.2%. The aim of the present study was to assess the impact on patient’s quality of life and symptoms of Flower pollen extract in association with vitamins (Deprox 500®) in comparison with Serenoa repens 320 mg (Permixon 320 mg® by Pierre Fabre) in patients with CP/CPPS. Methodology: All consecutive patients, with a diagnosis of CP/CPPS, referred to our center from January to August 2016, were screened to be enrolled in this single-center, randomized, controlled trial. The main outcome measure was the evaluation of IPSS/NIHCPSI (International Prostatic Symptom Score/NIH-Chronic Prostatitis Symptom Index) score variation and the assessment of the quality of life and symptoms at the end of the therapy. The second outcome measure was the evaluation of the comorbidity role in the CP/CPPS therapy. 63 patients were analyzed; patients were randomized into two groups: 29 patients were treated with Deprox 500® 2 tablets/day for 6 weeks and 34 patients with Serenoa repens 320 mg, 1 tablet/day for 6 weeks. Results: The mean score variation for IPSS was -12.7 ± 4.3 in the Deprox 500® group and -7.8 ± 4.7 in the Serenoa repens group (p=0.0005) while for NIH-CPSI was -17.3±3.1 in the Deprox 500® group and -13.6±4.8 in the Serenoa repens group (p=0.0016). By accounting only the symptoms part of NIH-CPSI questionnaire, the mean score variation reported was -11.5±2.5 in the Deprox 500® group and -9.02±4.0 in the Serenoa repens group (p=0.009321). Furthermore, analyzing the comorbidity subgroups, in patients with hypertension, the mean IPSS score variation was -14.3±3.2 in the Deprox 500® group and - 9.02±4.0 in the Serenoa repens group. Conclusion: In conclusion, in patients with CP/CPPS, Deprox 500® improves IPSS and NIH-CPSI scores up to 74.5% and 84.5% respectively. Furthermore, in patients with hypertension, the antioxidant effect of Deprox 500® reduces the mean IPSS score of 82.7%.