2-Substituted Benzoxazoles as Potent Anti-Inflammatory Agents: Synthesis, Molecular Docking and In Vivo Anti-Ulcerogenic Studies

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the commonly used therapeutic interventions of inflammation and pain that competitively inhibit the cyclooxygenase (COX) enzymes. Several side effects like gastrointestinal and renal toxicities are associated with the use of these drugs. The therapeutic anti-inflammatory benefits of NSAIDs are produced by the inhibition of COX-2 enzymes, while undesirable side effects arise from the inhibition of COX-1 enzymes. Objectives: In the present study, a new series of 2-substituted benzoxazole derivatives 2(a-f) and 3(a-e) were synthesized in our lab as potent anti-inflammatory agents with outstanding gastro-protective potential. The new analogs 2(a-f) and 3(a-e) were designed depending upon the literature review to serve as ligands for the development of selective COX-2 inhibitors. Methods: The synthesized analogs were characterized using different spectroscopic techniques (FTIR, 1HNMR, 13CNMR) and elemental analysis. All synthesized compounds were screened for their binding potential in the protein pocket of COX-2 and evaluated for their anti-inflammatory potential in animals using the carrageenan-induced paw edema method. Further 5 compounds were selected to assess the in vivo anti-ulcerogenic activity in an ethanol-induced anti-ulcer rat model. Results: Five compounds (2a, 2b, 3a, 3b and 3c) exhibited potent anti-inflammatory activity and significant binding potential in the COX-2 protein pocket. Similarly, these five compounds demonstrated a significant gastro-protective effect (p<0.01) in comparison to the standard drug, Omeprazole. Conclusion: Depending upon our results, we hypothesize that 2-substituted benzoxazole derivatives have excellent potential to serve as candidates for the development of selective anti-inflammatory agents (COX-2 inhibitors). However, further assessments are required to delineate their underlying mechanisms.

Meloxicam efficacy and safety in treatment of pain syndromes of different localization according to domestic studies

More than 500 million people worldwide suffer from osteoarthritis (OA). Neck and low back pain (LBP) is one of the most common reasons for visiting a general practitioner to receive primary medical care in different countries. The prevalence of chronic LBP varies from 4% to 20%, and increases linearly from the third decade to 60 years, and stabilizes in the seventh decade of life. According to the latest published clinical guidelines of the Russian Association for the Study of Pain, nonsteroidal anti-inflammatory drugs (NSAIDs) are used in minimally effective doses and a short course to relieve acute musculoskeletal pain. The ratio of the NSAIDs activity associated with cyclooxygenase (COX) – COX-1 / COX-2 – inhibition allows us to evaluate their potential toxicity. The smaller this value, the more selective the drug is against COX-2, and the less toxic it is. Meloxicam belongs to the predominantly selective COX-2 inhibitors. In the Russian market, meloxicam of domestic production - Amelotex® is widely prescribed. Several studies have shown the high efficacy and safety of meloxicam in the treatment of pain syndromes with different localizations (LBP, neck pain of vertebrogenic nature, OA, etc.), it can be recommended for elderly patients, patients with comorbid diseases such as arterial hypertension (AH), diabetes mellitus, gastrointestinal tract pathology. Meloxicam has a good efficacy and safety profile, a pronounced symptom-modifying effect.

Synthesis and Biological Evaluation of Some Novel Pyrrole Derivatives

The Pyrrole is one of the significant classes of heterocyclic mixes having pharmacological and natural exercises, for example, antibacterial, antifungal, anthelmintic. The subbed pyrroles with chose functionalities at various position fill in as antecedents for the combination of different new functionalities. Pyrrole has additionally indicated wide organic exercises, for example, treatment of hyperlipidemias, mitigating, COX1/COX-2 inhibitors, 6 cytotoxic action against strong tumor model and assortment of marine and human models. A progression of new Schiff base (E)- N'- Substituted benzylidene-1H-pyrrole-2-carbohydrazide subsidiary (3a-3j) were combined by the response of 1H-pyrrole-2-carbohydrazide and fragrant aldehyde within the sight of ethanol with barely any drops of frosty acidic corrosive. The response blend was observed by TLC and recrystallized from wanted dissolvable. FTIR, 1HNMR, mass spectral and natural investigation were affirmed the structure of the blended mixes. All orchestrated mixes were screened against traditional strains for their antibacterial, antifungal and anthelmintic tasks: gram positive is B.subtilis, and S.aureus and gram negative are E. coli. Antifungal movement was screened against C. Albicans and A. niger and anthelmintic movement was screened against M. konkanensis and P. corethruses. The outcomes uncovered that 3f, 3g and 3i display increasingly strong action against the both two microorganism (gram negative and gram positive bacteria) on the opposite side compound 3a, 3g and 3h show progressively intense movement against the two growths (C. Albicans and A. niger) and compound 3c and 3d having most powerful movement with mean paralyzing time of 11.27 mins and 15.83 mins and mean death time of 19.25 mins and 24.45 mins individually when contrasted with standard medication.