Synthesis and Characterization of Mannich‐Derived 1,4‐Naphthoquinones From Lawsone: Photophysical Properties, Molecular Docking, BSA/DNA Interactions, and Antioxidant Activity

Abstract

ABSTRACT The present study focuses on the synthesis of eight novel 2‐hydroxy‐1,4‐naphthoquinone (lawsone) derivatives in moderate to high yields (31%–90%) via the Mannich reaction. The structures of the synthesized compounds ( 1–8 ) were characterized using a combination of analytical techniques, including HRMS, as well as 1 H and 13 C NMR spectroscopy. DNA and BSA binding interactions, along with the antioxidant activities of the newly synthesized 1,4‐naphthoquinone derivatives, were systematically evaluated to assess the influence of various substituent groups on their biological performance. Among the tested compounds, compound 2 , bearing a para‐methyl substituent, exhibited the strongest DNA binding affinity with a binding constant of K b = 4.33 × 10 5 M − 1 . Additionally, ethidium bromide (EB) displacement assays were performed, and corresponding K sv values were calculated to further elucidate the mode of DNA interaction. BSA binding studies also revealed distinct K sv values for each compound. Evaluation of antioxidant properties demonstrated that all derivatives exhibited concentration‐dependent radical scavenging activity within the range of 6.25–200 µg/mL. Notably, compound 8 exhibited superior antioxidant performance, displaying approximately twice the activity of standard antioxidants. Molecular docking studies were performed on compounds exhibiting the highest biological activity in vitro, and their binding properties and interaction profiles to target proteins were investigated.