Cholinesterases Inhibition, Anticancer and Antioxidant Activity of Novel Benzoxazole and Naphthoxazole Analogs

Abstract

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.

Coumarin–azasugar–benzyl conjugates as non-neurotoxic dual inhibitors of butyrylcholinesterase and cancer cell growth

“…Dual ChE and cancer cell growth inhibition activity have been observed for sunitinib 59 (a cancer medication approved by the FDA) and other heterocyclic compounds. 60 To investigate whether our compounds exhibit such dual activities, their antiproliferative activities were evaluated on six human cancer cell lines, namely, A549 (lung cancer), HBL-100 (breast cancer), HeLa (cervix cancer), SW1573 (lung cancer), T-47D (breast cancer), and WiDr (colon cancer) after 48 hours of exposure, following the guidelines of the US National Cancer institute (NCI). 61 The results for the inhibition of cancer cell proliferation are presented in Table S1,† which are expressed as concentration of 8a–8e , 10 , 11 , 17a–17e , 20 , and 21 required to reduce the cancer cell growth by 50% (GI 50 ).…”

Research Progress of Benzothiazole and Benzoxazole Derivatives in the Discovery of Agricultural Chemicals

“…More importantly, when pests (such as armyworms [ 20 ], locusts [ 21 ], and walkers [ 22 ]) break out in large areas, the use of highly efficient chemical pesticides is the most effective strategy for rapid pest control [ 23 ]. However, long-term use of traditional agrochemicals will not only pollute the environment but also increase the resistance of pathogens [ 24 ], resulting in more difficult management of plant diseases, insects, and weeds [ 7 , 25 , 26 ]. Therefore, the development of new agrochemicals with unique action mechanisms to replace traditional pesticides is an urgent problem to be solved in the management of plant diseases, pests, and grass diseases.…”