Abstract:
Rheumatoid Arthritis is a chronic polyarthritic autoimmune condition associated with
joint erosion and synovial hyperplasia. Bone resorption in RA is a characteristic of
disease pathogenesis. RANKL signaling pathway is the main pathway involved in bone
resorption via osteoclastogenesis. Many factors activated downstream RANKL signaling
pathway exhibit elevated expression levels in RA and have been targeted for therapeutic
purposes. In this study, protein expression profiling of human carbonic anhydrase II, m Calpain, NFATc3 and TNF-alpha have been elucidated by using the technique of western
blotting. The results showeded their increased expression in the serum of RA patients.
Furthermore, since these proteins are inflammatory markers and inflammation is tightly
associated with oxidative stress, the DNA damage status due to this oxidative stress is
assessed in this study using comet assay. The results showeded that lymphocytes from
RA patients demonstrate detectable DNA damage. Moreover, in-silico virtual screening
has been used to screen the DrugBank for the identification of new hit compounds
exhibiting the potential to target human carbonic anhydrase II and inhibit its activity. For
this, docking and pharmacophore modeling approaches were used. Three new hit
compounds were elucidated. First one, Supiride, belongs to a class of
Benzenesulphonamides which is the mostwell-studied class of compounds known till
now. The other two compounds, alfuzosin and Prazosin are quinzolamines, which is a
novel prediction since compounds of this class have never been reported as CAIs nor
used for the treatment of RA
