Naphthoquinone-based chalcone hybrids and derivatives: synthesis and potent activity against cancer cell lines

Abstract

Novel naphthoquinone-based chalcones were prepared from the reaction between 3-bromo-nor-blapachone and amino-chalcones. Lapachone derivatives are also described here. All the substances were evaluated against cancer and normal cell lines and several compounds demonstrated potent antitumor activity.Scheme 1 Structural modification of the prototype lapachones.Scheme 2 Synthesis of the chalcone intermediates 1-6. This journal isScheme 5 Synthesis of the hydrazone derivatives 29-31, 33, 35, 37 and 39. (i) To obtain compound 26: H 2 SO 4 , 27: I 2 , Py, CH 2 Cl 2 , 0 C, 28: Br 2 , CH 2 Cl 2 . This journal isView Article Online a Results obtained by nonlinear regression for all assayed cell lines from three independent experiments (deviations in parenthesis).Scheme 7 Strategy used to obtain new antitumor naphthoquinonoid compounds.This journal is

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

“…The last compounds evaluated were asymmetric α-lapachone 48 and 49 and these substances were inactive. As recently described by us [45], the asymmetric α-lapachone derivatives are inactive against several cancer cell lines evaluated. Herein, we tried to improve their activities using the approach of insertion of the chalcogen in these quinones, but the strategy failed.…”

“…Synthesis of various antitumor compounds from 18 was reported, as for instance, arylamino and alkoxy substituted nor-β-lapachone [26], lapachones in the presence of 1,2,3-triazole moiety [44] and hybrids with chalcones [45]. The unpublished arylamino substituted lapachone 19 bearing a terminal alkyne group was prepared based on the previously described compounds possessing activity against cancer cell lines [26].…”

Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells

“…Redox center, A- and C-ring modifications of naphthoquinone prototypes, such as, for instance, β-lapachone and NβL, were the subject of a study by us [13,31]. We have discovered several nor-β-lapachone derivatives with highlighted antitumor activity (Scheme 1) [28,32,33,34,35,36].…”

Artificial Intelligence Recognizes β-Lapachone as an Allosteric 5- Lipoxygenase Inhibitor

“…As counter screen, we next tested 1 against Escherichia coli and Staphylococcus aureus, given their sensitivity to oxidative stress induced by reactive oxygen species-producing chemicals. [33][34][35][36] No phenotypic effects were observable at concentrations up to 50 µM of 1 (cf. Supporting Information).…”