In silico design of colchicine-based bioisosteric inhibitors of tubulin for the treatment of rheumatoid arthritis.

The super-saturation of serum with monosodium urate due to hyperuricemia is the core metabolic disorder of rheumatoid arthritis. When the serum urate concentration is ≥7 mg/dl, this results in the crystallization of monosodium urate in serum at body temperature (37˚C/98.6˚F). Colchicine (COL) is considered to be a first‑line medication for acute arthritis when NSAIDs are contraindicated. COL causes severe side effects, including diarrhea, nausea, cramping, abdominal pain and vomiting, in humans. Experimental studies have additionally demonstrated the presence of mutagenic and reproductive effects in humans. In the present study, molecular docking simulation techniqueswere used to design COL‑derived bioisosteric inhibitors, with the aim of designing an alternative treatment that exhibitedpotent anti‑arthritic activity and was free from the side effects associated with COL.