Separation and isolation of tautomers of 2-hydroxy-4-naphthoquinone-1-oxime derivatives by liquid chromatography: Antiproliferative activity and DFT studies

摘要: Reversed phase HPLC separation and isolation of isomers 2-hydroxy-4-naphthoquinone-1-oxime (Lwox) 3-methyl-2-hydroxy-4-naphthoquinone-1-oxime (Phox) have been investigated. Two distinct peaks are observed in the chromatogram Lwox assigned to ‘para’ tautomer; (3) ‘ortho’ 4-hydroxy-2-naphthoquinone-1-oxime (4). The tautomeric equilibrium 3 4 has manipulated by incrementally increasing pH mobile from 2.5 10.5, altering solvent polarity. At > 6.8 tautomers well-separated each other. There is no Phox between 10.5. Isolation carried out preparative HPLC, with obtained as ammonium bicarbonate adducts characterized LC-MS, FT-IR, UV-visible spectroscopy. Red-orange a paranaphthoquinone stretch at 1287 cm−1 charge transfer band 420 nm; yellow exhibits, similar 1246 absorption 406 nm. Compounds were screened for selective antiproliferative activity three cancer cell lines different tissue types (COLO 205 (human colorectal adenocarcinoma), U87 MG (glioblastoma astrocytoma) MIAPaCa-2 pancreatic carcinoma). Geometry-optimized structures (3′ 4′ Phox) computed using B3LYP method. Structures, 3′ 4.7 5.8 kcal mol−1 more stabilized than 4′, respectively, result hydrogen bond interaction 2-hydroxyl group nitrogen oxime.