Rheumatoid arthritis: advances in treatment strategies.

Rheumatoid arthritis (RA) is characterised by severe joint and bone damage due to heightened autoimmune response at the articular sites. Worldwide annual incidence and prevalence rate of RA is 3 cases per 10,000 population and 1%, respectively. Several genetic and environmental (microbiota, smoking, infectious agents) factors contribute to its pathogenesis. Although convention treatment strategies, predominantly Disease Modifying Anti Rheumatic Drugs (DMARDs) and Glucocorticoids (GC), are unchanged as the primary line of treatment; novel strategies consisting of biological DMARDs, are being developed and explored. Personalized approaches using biologicals targetspecific pathways associated with disease progression. However, considering the economic burden and side-effects associated with these, there is an unmet need on strategies for early stratification of the inadequate responders with cDMARDs. As RA is a complex disease with a variable remission rate, it is important not only to evaluate the current status of drugs in clinical practice but also those with the potential of personalised therapeutics. Here, we provide comprehensive data on the treatment strategies in RA, including studies exploring various combination strategies in clinical trials. Our systematic analysis of current literature found that conventional DMARDs along with glucocorticoid may be best suited for early RA cases and a combination of conventional and targeted DMARDs could be effective for treating seronegative patients with moderate to high RA activity. Clinical trials with insufficient responders to Methotrexate suggest that adding biologicals may help in such cases. However, certain adverse events associated with the current therapy advocate exploring novel therapeutic approaches such as gene therapy, mesenchymal stem cell therapy in future.

Synthesis and Biological Evaluation of 2-(Halophenyl)benzoxazole-5-Carboxylic Acids as Potential Anti-Inflammatory and Cytotoxic Agent with Molecular Docking Studies.

2-Halogenatedphenyl benzoxazole-5-carboxylic acids with mono-halogen (chloro, bromo and fluoro) substituted at ortho-, meta- and para-positions on the phenyl ring were designed and synthesized based on significance of presence of halogen in increasing number of marketed halogenated drugs and importance of benzoxazoles. These 2-alogenatedphenylbenzoxazole-5-carboxylic acids and their methyl esters were screened for anti-inflammatory activity, and cytotoxicity. 2-(3-Chlorophenyl)benzoxaole-5-carboxylic acid (6b) exhibited significant anti-inflammatory activity with IC50 values of 0.103 mM almost equivalent to the standard drug ibuprofen (0.101 mM). 2-(4-Chlorophenyl)benzoxaole-5-carboxylic acid (6c) showed excellent cytotoxic activity against 22Rv1 cells (human prostate carcinoma epithelial cell lines) with IC50 value of 1.54 µM better than that of standard drug doxorubicin having IC50 value of 2.32 µM. More importantly, the selectivity index of this potential molecule was found to be 57.74. Molecular docking analysis resulted in good binding interactions of these compounds with their respective biochemical targets viz. Cyclooxygenase-2 and aldo-keto reductase IC3.