Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics

Abstract

A series of new chiral benzisoselenazol-3(2H)-ones and their corresponding diselenides bearing an o-amido function substituted on the nitrogen atom with various aliphatic and aromatic moieties were synthesized. All derivatives representing pairs of enantiomers or diastereoisomers were obtained to thoroughly evaluate the three-dimensional structure–activity correlation. First, bensisoselenazol-3(2H)-ones were synthesized by reacting 2-(chloroseleno)benzoyl chloride with an appropriate enantiomerically pure amine. Then, the Se–N bond was cleaved by a reduction–oxidation procedure using sodium borohydride and then air oxidation to obtain the corresponding diselenides. All derivatives were tested as antioxidants and anticancer agents. In general, the diselenides were more reactive peroxide scavengers, with the highest activity observed for 2,2′-diselenobis[N-(1S,2S)-(-)-trans-2-hydroksy-1-indanylbezamide]. The most cytotoxic derivative towards human promyelocytic leukemia HL-60 and breast cancer MCF-7 cell lines was N-[(1S,2R)-(-)-cis-2-hydroksy-1-indanyl]-1,2-benzizoselenazol-3(2H)-one. The structure–activity relationship of the obtained organoselenium derivatives was discussed.

Facile synthesis of chiral phenylselenides as novel antioxidants and cytotoxic agents

“…As presented in our previous papers, 20 the presence of the indanyl substituent attached to the nitrogen atom of benzisoselenazolones and corresponding diselenides also enhances the cytotoxic effect. A comparison of all 3 types of indanyl Se-derivatives is presented in Table 4 .…”

“…For this purpose, we have slightly modified the procedure proposed by Młochowski and co-workers (Method A, Scheme 1 ). To a solution of phenyl magnesium bromide, formed by refluxing PhBr and Mg 0 in diethyl ether, appropriate N -substituted benzisoselenazolone 5 (obtained previously through the reaction of 2-(chloroseleno)benzoyl chloride with an appropriate enantiomerically pure amine 20 ) dissolved in Et 2 O or THF was added ( Scheme 2 ).…”

Synthesis of New Chiral β-Carbonyl Selenides with Antioxidant and Anticancer Activity Evaluation—Part I

“…In our research, we synthesized and evaluated the antioxidant and anticancer properties of various N-substituted benzisoselenazolones, including chiral N-terpenyl and aminoacid derivatives [18]. We have additionally explored the possibility of improving their catalytic properties by converting the Se-N bond into different functional groups that could also imitate the active selenol of L-Sec, like corresponding diselenides 5 [19], phenylselenides 6 [20], seleninic acids, and their potassium salts 7 [21]. Herein, we have further differentiated the primary structure by synthesizing a series of new N-functionalized β-carbonyl selenides 8 (Figure 1).…”

Introduction of Methyl Group in Substituted Isoselenazolones: Catalytic and Mechanistic Study

“…The Se–N heterocyclic benzisoselenazolones create a wide group of derivatives with proven bioactivities . The work in recent times has been more devoted toward organoselenium compounds with intriguing biological activities. − Built upon this basis, a number of procedures for the formation of C–Se and Se–N bonds were achieved such as the well-known annulation reaction of a multistep 2-(chloroseleno)­benzoyl chloride with an appropriate primary amine as prepared from anthranilic acid by sequential diazotization, selenation, and chlorination . Other conventional strategies are the ortho -lithation benzanilide route, copper-catalyzed synthesis of Se–N heterocycles with halo-substituted ortho -benzamides in the presence of a base, and nickel-catalyzed dehydrogenative direct selenation of C­(sp 2 )–H bonds with elemental selenium in air .…”