Environmentally benign synthesis of substituted pyrazoles as potent antioxidant agents, characterization and docking studies

Oxidative stress is an important cause of neurogenerative diseases; treatment with a reliable antioxidant with no side effects is a potential tool to overcome with such diseases. The aim of this study is to explore new and effective antioxidants and their mechanism; in this context, the manuscript demonstrates the greener approach for the synthesis of series of novel thiophene-pyrazole hybrids, 5(a–m) through [3 + 2] annulation of chalcones, 3(a–g) and phenylhydrazine hydrochloride, 4(a–b) in citrus extract medium in the presence of tetrabutylammonium bromide. The structures were confirmed by spectroscopic and crystallographic studies and further screened in vitro for their free radical scavenging activities. Preliminary assessment results show that, among the synthesized series, compounds 5c, 5d, 5f, 5i, 5j, 5l, and 5m have potent antioxidant activities. Docking studies reveal that the ligands 5e, 5f, 5m, and 5q bind to superoxide dismutase at the Cu–Zn domain and thereby increase its activity and reduce reactive oxygen species; therefore, these ligands might be better antioxidant molecules which could down and regulate the oxidation stress within the body.