Synthesis and docking study of diaryl-isothiazole and 1,2,3-thiadiazole derivatives as potential neuroprotective agents

Neuroinflammation has been implicated in pathophysiology of many neurodegenerative diseases. The p38 MAP kinase signaling pathway and COX-1 have active roles in initiation and perpetuation of neuroinflammatory process which have deteriorating effects on neurons. In order to develop new anti-neuroinflammatory compounds some 4-aryl-5-(methylthiophen-2-yl) isothiazoles and 5-aryl-4-(methylthiophen-2-yl)-1,2,3-thiadiazoles were synthesized. Docking studies have revealed that these structures could be potential mutual inhibitors of p38α and COX-1 and could be considered for neuroprotective effects. In order to assess CNS penetrability of these compounds, a QSAR model of blood–brain barrier penetration has been developed and LogBB of compounds has been predicted. All compounds showed LogBB as greater than zero which indicates their potential CNS penetrability.