Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 13, Issue 3, 2014

The idea of regulatory T cells (Tregs) lost its popularity during the 1980s and 1990s, since immunologists failed to elucidate how the innate regulation of immunological reactions worked. The entire re-evaluation of the Tregs was supported due to the increasingly influential and state of the art immunological techniques, as cell sorting and also the expanding understanding of the immune system and its functions which aided in attaining a greater insight into the mechanisms of regulation and suppression. Many researchers nowadays have demonstrated that Tregs may well have therapeutic possibilities for the treatment of autoimmune diseases if it was a possibility to isolate and infuse these Tregs into patients, preferably without any harmful side effects. Therefore, modulation of Tregs as well as their generation is being researched since they were proposed as therapeutic interventions in several disease sceneries, nonetheless, sometimes with disastrous consequences. Consequently, a full and complete understanding of the exceptional biology of human Tregs is fundamental for the accurate interpretation of found data, before therapeutic interventions can be undertaken. This literature study gives an overview of the current accessible information on the topic of the characterization, the generation, regulation and functions of the Inducible Treg populations and their subsets in the human immune system.

The human body is constantly exposed to the risk of traumatic lesions. ROQUETTE Schizochytrium sp. (SCs) is a marine microalgae containing large amounts of health-valuable nutrients, more particularly polyunsaturated fatty acids such as docosahexaenoic acid. SCs 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-O-tetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered after incisional wound healing of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of SCs had significant effects on macroscopic score of skin inflammation. It had also efficient effect on healing process and duration of wound healing with a dose-response by oral administration and a maximal effect observed from the lowest to the highest dose by topical application. These findings suggest that administration of SCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

Objective: Investigation of the pharmacological potential of Tetrahydrofurano/pyrano quinoline and Benzo [b]furoindolyl derivatives in acute inflammation, pain and oxidative stress. Methods: Tetrahydrofurano/ pyrano quinoline and Benzo[b]furoindolyl were evaluated for anti-inflammatory activity by carrageenan-induced hind paw edema in rats. Analgesic activity in mice was assessed by both peripheral and central analgesic models. The free radical scavenging activity of the synthetic compound was analyzed by the in vivo antioxidant assays, by measuring the antioxidant enzymes such as Superoxide dismutase (SOD), Catalase and Peroxidase from the liver homogenate and the in vitro antioxidant activity was evaluated by DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assay. Results: The compounds had substantially inhibited the inflammation induced by subcutaneous carrageenan injection. The same compounds had demonstrated remarkable central and peripheral analgesic activity with potent free radical scavenging activity as evident from both in vitro and in vivo antioxidant assays. Conclusion: Tetrahydrofurano/pyrano quinoline and Benzo[b]furoindolyl derivatives exhibit varied pharmacological activities that include anti-inflammatory, analgesic and antioxidant activity.

In an attempt to find a new class of anti-inflammatory agents, a series of novel benzamides 3 (ab1-ab16) was synthesized by utilizing some arylideneoxazolones 2(az1-az4) having 2-acetyloxyphenyl substitution on their second position. IR, 1H-NMR, 13C NMR and HRMS, confirmed the structures of these synthesized compounds. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11 and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

The mutual prodrugs of aceclofenac with various naturally available antioxidants; menthol, thymol, eugenol, guiacol and vanillin have been synthesized by the DCC coupling method, purified and characterized by spectral data, as well as, partition coefficient, solubility and hydrolytic studies. The title compounds have more lipophilic character as compared to the parent moieties and good stability in acidic environment, which is prerequisite for the oral absorption of the drug. Under gastric as well as intestinal pH conditions these prodrugs showed variable susceptibility towards hydrolysis. The synthesized derivatives were evaluated for antiinflammatory, analgesic activities and ulcerogenic potential. Prodrug showed improved solubility in organic solvents, which implies lipophilic character of ester prodrugs and were also found to be chemically stable in acidic environment. The aceclofenac mutual prodrugs showed improved analgesic and anti-inflammatory activities with reduced ulcerogenicity.