Exploration of thiosemicarbazone-quinolone hybrids over in-silico, antioxidant, and zebrafish embryo toxicity studies

Abstract

In this study, we successfully synthesized a series of acetyl quinolone thiosemicarbazones (5a-d, 6a-d) using a simple work-up procedure yielding column-free products. The structures of the synthesized compounds were confirmed by various spectroscopic techniques, including 1H, 13C, and 2D NMR, along with FT-IR. Detailed 2D NMR analyses such as COSY, HSQC, and HMBC were also performed. The biological activities were evaluated through in-vitro, in-vivo, and in-silico studies. In-vitro antioxidant properties were assessed using radical scavenging assays, revealing significant activity for compounds 5b and 6b, likely due to the aromatic ring substitution in the thiosemicarbazide side chain. In-vivo zebrafish embryo toxicity studies indicated minimal toxicity for these compounds. Additionally, in-silico studies showed that compounds 5b and 6b have good binding energies for proteins 2C0U, 3NM8 and 2X08. Further the DFT study of HOMO and LUMO energy gap is small for 5b and 6b. These findings suggest that acetyl quinolone thiosemicarbazones are promising candidates for various biological applications due to their potent antioxidant activity and low toxicity.