INTERACTION OF (4E)-3-ALKYL(BENZYL)AMINO-4-(HYDROXYIMINO)NAPHTHALENE-1(4H)-ONES WITH 2,2-DIHYDROXY-1,3-INDANEDIONE

Abstract

Many natural and synthetic quinone, including naphthoquinone derivatives, have some valuable properties. They are known as dyes, antibiotics, vitamins, and antioxidants. Some naphthoquinone derivatives act as cytostatic and antitumor reagents. However, the reduction of the quinoid fragment to the semiquinone radical and, as a consequence, the formation of toxic anion radicals, makes these substances cardiotoxic. The replacement of one or both carbonyl groups with the imino fragment can be one of the ways to solve this problem because iminoquinones have a weak redox cycle. This paper presents the results of the MTT test (primary screening for antitumor activity) of some 3-arylamino-1,4-naphthoquinone-4-oximes which were synthesized earlier. It has been shown that (4E)-4-(hydroxyimino)-3-(p-ethoxyphenylamino)naphtho-1(4H)-one and (4E)-4-(hydroxyimino)-3-(p-tolylamino)naphtho-1(4H)-one are most active against the colon adenocarcinoma and chronic myeloid leukemia in the tumor cell lines, respectively. We have performed the oximation reaction of 2-alkyl(benzyl)amino-1,4-naphthoquinones with hydroxylamine in ethanol to obtain a series of (4E)-3-alkyl(benzyl)amino-4-(hydroxyimino)naphthalene-1(4H)-ones. The reactions of synthesized products with 2,2-dihydroxy-1,3-indanedione (ninhydrin) have been studied under various conditions, i.e., in acetic acid under moderate heating and in dimethyl sulfoxide in the presence of methanesulfonic acid at different temperatures. It has been demonstrated that the interaction of (4E)-3-alkyl(benzyl)amino-4-(hydroxyimino)naphthalene-1(4H)-ones with ninhydrin in acetic acid leads to (6E)-5-alkyl(benzyl)amino-6-гhudroxyimino-4b,11b-dihydroxy-4b,5-dihydrobenzo[f]indeno[1,2-b]indol-11,12(6H,11bH)-diones. More severe conditions (dimethyl sulfoxide, methanesulfonic acid, and heating) leads to a mixture of products, the main of which are 1–alkyl-3'H-spiro[benzo[f]indole-2,1’-isobenzofuran]-3,3’,4,9(1H)-tetraones and 13-alkyl(benzyl)benzo[f]isochromeno[4,3-b]indole-5,7,12(13H)-triones. The yields of the products depend on the chosen temperature regime of the reaction. The structure of all synthesized compounds is confirmed by the physico-chemical methods, i.e., 1H and 13C NMR spectroscopy, IR spectroscopy, high-resolution mass spectrometry, spectrophotometry and elemental analysis. For citation: Gornostaev L.M., Rudenko D.S., Kirik S.D., Krasnov V.I. Interaction of (4E)-3-alkyl(benzyl)amino-4-(hydroxyimino)naphthalene-1(4H)-ones with 2,2-dihydroxy-1,3-indanedione. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 5. P. 24-35. DOI: 10.6060/ivkkt.20246705.7015.