57093-27-3Relevant academic research and scientific papers
SYNTHESIS OF ACETYLATED GLYCOSIDES OF HYDROXYNAPHTHOQUINONES
Polonik, S. G.,Tolkach, A. M.,Uvarova, N. I.
, p. 307 - 310 (1983)
A method is proposed for the synthesis of acetylated glycosides of hydroxynaphthoquinones.The condensation of D-glucose and D-galactose (tert-butyl orthoacetate)s with lawsone and lapachol has given the tetra-O-acetyl-β-D-glucopyranosides of lawsone and of lapachol and the tetra-O-acetyl-β-galactopyranoside of lawsone.The structures of the glycosides obtained have been confirmed by IR and 1H and 13C NMR spectroscopy.The structure of the lawsone acetylgalactopyranoside described previously has been corrected.
Lapachol acetylglycosylation enhances its cytotoxic and pro-apoptotic activities in HL60 cells
Alves, Ricardo José,Holzer, Anna-Katharina,Kisitu, Jaffar,Leist, Marcel,Marques, Lucas Bonfim,Ottoni, Flaviano Melo,Pinto, Mauro Cunha Xavier,Ribeiro, Juliana Martins,Souza-Fagundes, Elaine Maria,Weinlich, Ricardo,de Sousa, Fernanda S.,de Victo, Nathalia Cruz
, (2020/01/28)
Lapachol is a plant-derived naphthoquinone that kills several types of cancer cells. Derivatives of this molecule may therefore prove to be useful chemotherapeutic agents. In this study, we explored whether glycosylation increases the cytotoxic potency of lapachol towards HL-60 human leukemia cells. Two beta-glycosides were synthesized and characterized: LA4A (lapachol-β-glucoside) and LA4C (lapachol-N-acetylglucosamine-β-glucoside). The sugar moieties of both novel molecules were per-acetylated to facilitate cellular uptake. The IC50 values (in μM) for LA4A (5.7) and LA4C (5.3) were lower than those for lapachol (25). LA4A and LA4C triggered typical signs of apoptosis, such as the exposure of phosphatidylserine on the outside of cells, chromatin condensation, DNA fragmentation and a decrease of the mitochondrial transmembrane potential (ΔΨm) prior to cell lysis. Moreover, DNA fragmentation triggered by the lapachol-glycosides was reduced by pre-treatment with the caspase inhibitor, z-VAD-fmk. While LA4A and LA4C activated caspases-3, -8 and -9, lapachol failed to activate these apoptotic proteases, even when used at high concentrations. Finally, the toxicity of lapachol and its derivatives was also tested on non-tumor cells. We used human peripheral neurons (PeriTox test) to evaluate the side effect potential of these compounds. LA4C was clearly less toxic than LA4A. We conclude that LA4C had the most favorable profile as drug candidate (high tumor cell toxicity, reduced neurotoxicity). In general, this study shows that the cytotoxicity of lapachol towards HL-60 can be enhanced by glycosylation, and that the therapeutic ratio may be modified by the type of sugar added.
SYNTHESIS OF GLUCOSIDES OF 3-ALKYL-2-HYDROXY-1,4-NAPHTHOQUINONES
Polonik, S. G.,Tolkach, A. M.,Denisenko, V. A.,Uvarova, N. I.
, p. 310 - 313 (2007/10/02)
The condensation of D-glucose (tert-butyl orthoacetate) with 3-alkyl-2-hydroxy-1,4-naphthoquinones has yielded a series of acetylated glycosides of hydroxynaphthoquinones.It has been established that the time of the glycosylation reaction lengthens with an increase in the length and in the degree of branching of the side chain of the quinone.It has been shown that when the glycosides obtained are deacetylated cleavage of the glycosidic bond takes place with the formation of glucose and the corresponding quinone methyl ethers.Details of IR and 1H and 13C NMR spectra are given.
