Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 16, Issue 3, 2017

Background: Various mediators and anti-inflammatory drugs were used since from a long time but it is still a challenge for the medicinal chemists to treat or reduce the symptoms of inflammatory diseases. Most of the clinically used anti-inflammatory drugs such as NSAIDs, Coxibs and GCs are allied with considerable toxicity. Objective: The search of novel anti-inflammatory agent is not an ending process. Although the drug treatment has been improved steadily but yet, it is still there is a need to develop more potent therapeutic agents. Method: Reported literature survey has been studied to summarize the nitrogen containing moieties which were utilized as potential therapeutic agents. Results: A variety of N-heterocyclic analogs are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal and anti-HIV. However, numerous approaches were used to overcome the toxicity level such as co-administration with suitable agent/substance which provides protection against toxicity as well to synthesise new potent and safe anti-inflammatory drug. Conclusion: The present review summarizes the synthetic methodology and therapeutic potential of some N-heterocyclic analogs as potent anti-inflammatory agents.

Background: Due to the need and adverse effects associated with the available anti-inflammatory agents, an attempt was made to develop the new anti-inflammatory agents with better activity and lesser adverse effects. Objective: Synthetic approaches based on chemical modification of NSAIDs have been undertaken with the aim of improving NSAIDs safety profile. Method: In the present study, a series of thiazole derivatives (3a-3x) was synthesized and tested for its anti-inflammatory with analgesic and nitric oxide releasing properties. In this work, synthesis of molecules containing substituted diaryl ring on 5-membered thiazole ring with nitric oxide releasing moiety is described. Results: Out of the twenty four synthesized compounds, five compounds showed considerable anti-inflammatory and analgesic activity in comparison with the standard. Most of the synthesized compounds showed considerable nitric oxide-releasing property. The molecular docking study was used to rationalize binding interaction at the active site and the result showed good binding interaction. Conclusion: From the results of pharmacological studies, we conclude that the synthesized compounds have not only retained, but showed enhanced anti-inflammatory and analgesic profile.

Background: Low circulating levels of adiponectin are associated with the occurrence of infection after surgery in patients with cancer. Data are lacking on whether surgical stress is associated with a reduction in circulating levels of adiponectin. Furthermore, the relationship between oxidative stress and postoperative complications has not been investigated. Objective: The aim of this study was to evaluate the pre-, intra-, and postoperative levels of adiponectin in patients who underwent major abdominal surgery for malignancy and their association with postoperative complications. Methods: An observational, prospective, single-center study was conducted in patients undergoing abdominal surgery for cancer. Circulating levels of adiponectin and of two biomarkers of oxidative stress were measured preoperatively, at the end of surgery, 24 and 48 hours after surgery. Patients were divided into two groups: complicated (CL+) and uncomplicated (CL-), according to the Clavien-Dindo classification. Temporal patterns of adiponectin and markers of oxidative stress were followed at different time points. Results: Twelve patients were enrolled, seven with postoperative complications (CL+) and five without (CL-). The preoperative median levels of adiponectin were statistically different between CL+ and CL- groups (3.2 μg/ml vs 10.9 μg/ml; p=0.03). Levels of preoperative adiponectin were inversely related to the severity of postoperative complications (Rho= -0.68; p= 0.02). Pre-, intra- and postoperative levels of oxidative stress products were not statistically different between the two groups. Adiponectin levels decreased during surgery in both groups, while those of oxidative stress tended to increase. Conclusions: Preoperative adiponectin levels correlate with postoperative complications after cancer surgery.

Background: We have developed a new series of 36 substituted thiazole derivatives prepared via reaction of substituted benzothiazole-2-amine with substituted phenacyl bromide. Objective: This study was aimed to develop and successfully evaluate anti-inflammatory activity of substituted thiazole derivatives. Method: A new series of 36 substituted thiazole derivatives was synthesized and derivatives were characterized by analytical and spectrometric methods like IR, MS, and 1H NMR. The molecular docking was performed for all the synthesized thiazole derivatives to assess their binding affinities to COX-2 isozyme. The best compounds from docking study were subjected for their anti-inflammatory activity by using rat hind paw edema method. Results: Results from carrageenan-induced hind paw edema showed that compounds 3h, 5a, 5e, 9d, and 9h possess significant anti-inflammatory activity. The result from vascular permeability indicating inhibition of vascular permeability with compounds 3h and 9h is significant and results from cotton pellet granuloma formation models show greater degree of inhibition with compounds 3h and 5a to contribute to their significant anti-inflammatory activity. Conclusion: This study provides successful development of novel thiazole derivatives. Their binding affinities to COX-2 enzyme were also confirmed, indicating that developed molecules are comparable to diclofenac and hence could be promising anti-inflammatory agents.

Background: Curcuma longa Linn, “the golden spice” is a common spice used in Southern Asia and Middle East countries. It has a history of ethnopharmacological use for its various activities like anti-septic, anti-inflammatory, anti-oxidant, anti-microbial, anti-cancer and so on. Objective: To investigate the effects of polar extract of C. longa (PCL) against monosodium iodoacetate (MIA) induced osteoarthritis in rat and to compare with curcuminoids, which are contemporarily believed to be the only active phytochemicals of C. longa for relieving pain in osteoarthritis. Method: Osteoarthritis in rats was induced by intra-articular injection of monosodium iodoacetate (MIA) in right knee. PCL or curcuminoids or tramadol was administered orally as single dose on the 5th day post MIA injection to rats. Weight bearing capacity and percentage inhibition of nociception of PCL treated groups were determined and compared with curcuminoids and tramadol (reference drug). In addition, gene expression levels of type II collagen and matrix metalloproteinases (MMP) in joint cartilage was measured by Reverse transcription polymerase chain reaction. Results: PCL significantly decreased the difference in weight distribution between left and right limb in a dose dependent manner. Anti-arthritic activity of PCL is evident from significant up regulation of type II collagen gene (COL2A1) and down regulation of MMP-3 and MMP-7. Conclusion: Polar extract of C. longa showed beneficial effects on joints by exhibiting antiosteoarthritic effects via maintaining equilibrium between anabolic and catabolic factors of joint cartilage.