Cholinesterases inhibition, anticancer and antioxidant activity of novel benzoxazole and naphthoxazole analogs

Abstrakt

Benzoxazole and naphthoxazole fused systems are found in many biologically active molecules. Novel benzoxazole and naphthoxazole analogs functionalized by the 2,4-dihydroxyphenyl moiety were designed, obtained and evaluated as a broad spectrum of biological potency compounds. Sulfinylbis[(2,4-dihydroxyphenyl)methanethione] or its analogs and 2-aminophenols or 1-amino-2-naphthol were used as starting reagents. 4-(Naphtho[1,2-d][1,3]oxazol-2-yl)benzene-1,3-diol was identified as the most promising compound of the nanomolar activity against AChE (IC50 = 58 nM) of the mixed-type inhibition and of the moderate activity against BChE (IC50 = 981 nM). The higher antiproliferative potency against a panel of human cancer cell lines for naphtho[1,2-d][1,3]oxazoles than for benzoxazoles was found. The activity of the analog with chlorine atom was in the range of 2.18–2.89 µM (IC50) against all studied cells and it is similar to that of cisplatin studied comparatively. Moreover, this compound was not toxic at this concentration to human normal breast cells and keratinocytes. For some compounds it also has proved antioxidant properties at the level of IC50 = 0.214 µM, for the most active compound. The lipophilicity of all compounds, expressed as log p values, is within the range recommended for potential drugs. The biological activity profile of the considered analogs and their lipophilic level justify the search for agents used in AD or in anticancer therapy in this group of compounds.

Autorzy

Monika Karpińska
Monika Karpińska
Małgorzata Juszczak
Małgorzata Juszczak
Aneta Grabarska
Aneta Grabarska
Joanna Wietrzyk
Joanna Wietrzyk
Elżbieta Krajewska-Kułak
Elżbieta Krajewska-Kułak
Marek Studziński
Marek Studziński
artykuł
MOLECULES
Angielski
2022
27
23
8511
otwarte czasopismo
CC BY 4.0 Uznanie autorstwa 4.0
ostateczna wersja opublikowana
w momencie opublikowania
2022-12-03
140
4,6
0
2