Biological activity of non-radical stable radical of a pyridazine-sulfonamide aminophenol-type compound

• Published in: New journal of chemistry 2022-09, Vol.46 (37), p.17951-17957
• Main Authors: Chatterjee, Himadri Sekhar, Maity, Suvendu, Halder, Satyajit, Ghosh, Prasanta, Jana, Kuladip, Mahapatra, Pradip Kumar, Sinha, Chittaranjan
• Format: Article
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d2nj03308a

4-(3,5-Di- tert -butyl-2-hydroxyphenylamino)- N -(6-methoxypyridazin-3-yl)benzenesulfonamide ( LSO AP H 2 ) is an 2-aminophenol-appended, redox-non-innocent molecule. It was characterized structurally by spectroscopy and its structure was confirmed by single-crystal X-ray diffraction. The o -iminosemiquinonate monoanion ( LSO ISQ ) was obtained by one electron-oxidation and confirmed by electron paramagnetic resonance (EPR) spectroscopy and UV-vis spectroscopy. Cyclic voltammetry showed two consecutive redox couples: o -amidophenolate/ o -iminosemiquinonate monoanion ( LSO AP H 2 /LSO ISQ ) and o -iminosemiquinonate monoanion/ o -benoquinone ( LSO ISQ /LSO IQ ). The radical features of LSO ISQ in air were supported by EPR spectroscopy ( g = 2.005) in a solution at room temperature. Computation based on density functional theory revealed the spin density to be localized on LSO ISQ due to formation of the o -iminosemiquinonatemonoanion radical. The in vitro toxicity of LSO AP H 2 and LSO ISQ was estimated against human cancer cell lines (HepG2, MDA-MB 231, HeLa) and a human normal cell line (WI-38). The cellular metabolic activity of LSO AP H 2 and LSO ISQ were determined using the MTT assay using the cell lines stated above. LSO AP H 2 and LSO ISQ enhanced cellular levels of reactive oxygen species in human cancer cell lines, which culminated in the inactivation/death of cancer cells. LSO ISQ was more effective than LSO AP H 2 as an anticancer agent. A redox-non-innocent 2-aminophenolate derivative 4-(3,5-di- tert -butyl-2-hydroxyphenylamino)- N -(6-methoxypyridazin-3-yl)benzenesulfonamide ( LSO AP H 2 ) is more activity against cancer cell lines than one electron-oxidized form o -iminosemiquinonate monoanion ( LSO ISQ ).