Potential effect of novel thiadiazole derivatives against radiation induced inflammation with low cardiovascular risk in rats

Abstract The aim of the present study is to explore new selective anti-inflammatory compounds with low cardiovascular risk. Twelve thiadiazole derivatives incorporating different amino acid moieties were newly synthesized ( 4 – 15 ) as potential agents risks through dual COX-2/MPO inhibition. Compounds initially screened for their effect by assay COX-2, most potent 6 , 8 further tested COX-1 inhibition, myeloperoxidase MPO activity well total nitric oxide content NO in heart irradiated rats. Cardiac toxicity was evaluated creatine kinase-MB (CK-MB), troponin-I (Tn-I) and lactate dehydrogenase (LDH). Celcoxcib used reference drug. S-(5-((4-Methoxybenzylidene)amino)-2,3-dihydro-1,3,4-thiadiazol-2-yl)2-amino propanethioate (5) least cardiotoxicity effect. It exhibited IC 50 0.09 µM on COX-2 inhibition very COX-1. Troponin I elevated 11% using compound 5 non-irradiated Moreover, showed 73% reduction level. Results supported molecular docking into active sites enzymes have more insights about possible both enzymes.