Evaluation of toll-like receptor inhibition by novel thymoquinone analogues as potential remedy for diabetic nephropathy.

Diabetic nephropathy (DN) is a major worldwide cause of chronic kidney disease and end-stage renal failure, impacting approximately 20-50% of individuals with diabetes. DN frequently progresses to end-stage renal disease. The prevalence of DN continues to increase significantly, accompanied by rising rates of death and cardiovascular complications. To date, there is no specific drug approved exclusively for the treatment of diabetic nephropathy. In this work 13 novel disubstituted TQ analogues were synthesized, recrystallized and structurally verified via microanalytical and spectral data. Screening against TLR-4 activity was performed, the most potent disubstituted propyl ether TQ13 was subjected to more in-vivo biological investigations in STZ induced hyperglycemia rats. TQ13 showed anti-hyperglycemic, antioxidant, anti-inflammatory and antiapoptotic effects in addition to amelioration of kidney function markers, TLR-2 & TLR-4 activities. The findings of this investigational study suggest that disubstituted propyl ether TQ13 may represent a promising radio-stable renoprotective candidate in DN therapeutics which needs more tentative studies on toxicity and exact mechanism of action involving advanced staging pathways.