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 anti-inflammatory agents with low cardiovascular risks through dual COX-2/MPO inhibition. Compounds were initially screened for their anti-inflammatory effect by assay of COX-2, the most potent (4–6, 8) were further tested for COX-1 inhibition, myeloperoxidase MPO activity as well as total nitric oxide content NO in heart of irradiated rats. Cardiac toxicity potential was evaluated by assay of creatine kinase-MB (CK-MB), troponin-I (Tn-I) and lactate dehydrogenase (LDH). Celcoxcib was used as reference drug. S-(5-((4-Methoxybenzylidene)amino)-2,3-dihydro-1,3,4-thiadiazol-2-yl)2-amino propanethioate (5) was the most potent anti-inflammatory with the least cardiotoxicity effect. It exhibited IC50 0.09 µM on COX-2 inhibition with very low activity on COX-1. Troponin I was elevated by 11% using compound 5 in non-irradiated rats. Moreover, compound (5) showed 73% reduction in MPO level. Results were supported by molecular docking into the active sites of COX-2 and MPO enzymes to have more insights about the possible dual inhibition of compound 5 of both enzymes.

Design, synthesis, biological and computational screening of novel pyridine-based thiadiazole derivatives as prospective anti-inflammatory agents

“…These compounds have also exhibited promising activities in areas like anticancer [ [32] , [33] , [34] , [35] , [36] , [37] ]. Notably, Zaher et al (2022) and Maddila et al (2016) have contributed significant findings regarding pyridine derivatives' anti-inflammatory [ 38 , 39 ] and anticancer [ [40] , [41] , [42] , [43] ] effects, respectively, attributed to the presence of the thiadiazole ring within their chemical structures. Moreover, recent developments have seen the integration of pyridine and thiazole rings into lead compounds for anti-inflammatory purposes [ [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] ].…”