17241-45-1Relevant articles and documents
Inhibition of Staphylococcus aureus TetK and MsrA efflux pumps by hydroxyamines derived from lapachol and norlachol
Camara, Celso Amorim,Cavalcante-Figueredo, Maynara Rodrigues,Coutinho, Henrique Douglas Melo,Ferreira Matias, Edinardo Fagner,Figueiredo, Jakson Gomes,Figueredo, Fernando Gomes,Fonteles, Marta Maria de Franca,Parente, Rodrigo Emmanuel L. T.,Silva, Tania Maria Sarmento,Tintino, Saulo Relison,da Silva, Raimundo Luiz Pereira,de Morais Oliveira-Tintino, Cícera Datiane
, p. 149 - 156 (2021)
The present study aimed to evaluate the in vitro efflux pump inhibitory capacity of hydroxyamines derived from lapachol and norlachol, where compounds 3, 4, and 5 were tested against the S. aureus strains: RN4220 carrying the pUL5054 plasmid; and IS-58, endowed with the PT181 plasmid. The substances were synthesized from 2-hydroxy-quinones, lapachol and nor-lapachol obtaining the corresponding 2-methoxylated derivatives via dimethyl sulfate alkylation in a basic medium, which then reacted chemoselectively with 2-ethanolamine and 3-propanolamine to form the corresponding amino alcohols. The antibacterial action of the substances was quantified by determining the Minimum Inhibitory Concentration (MIC), while a microdilution assay was carried out to ascertain efflux pump inhibition of Staphylococcus aureus strains carrying the MsrA macrolide and the TetK tetracycline efflux pumps with the substances at a sub-inhibitory concentration. The results were subjected to statistical analysis by an ANOVA test and Bonferroni post hoc test. The MIC from the substances exhibited a value ≥ 1024 μg/mL. However, a significant reduction (p a supposed efflux pump inhibition. The tested substances demonstrated effectiveness at decreasing the MIC of erythromycin, tetracycline and ethidium bromide, potentially by inhibiting the MsrA macrolide and the TetK tetracycline efflux pumps present in the tested S. aureus strains.
Evans,Hoffman
, p. 1983 (1976)
Conjugation with polyamines enhances the antitumor activity of naphthoquinones against human glioblastoma cells
Rom?o, Luciana,Do Canto, Vanessa P.,Netz, Paulo A.,Moura-Neto, Vivaldo,Pinto, ?ngelo C.,Follmer, Cristian
, p. 520 - 529 (2018/06/04)
Glioblastoma multiform (GBM) is the most common and devastating type of primary brain tumor, being considered the deadliest of human cancers. In this context, extensive efforts have been undertaken to develop new drugs that exhibit both antiproliferation and antimetastasis effects on GBM. 1,4-Naphthoquinone (1,4-NQ) scaffold has been found in compounds able to inhibit important biological targets associated with cancer, which includes DNA topoisomerase, Hsp90 and monoamine oxidase. Among potential antineoplastic 1,4-NQs is the plant-derived lapachol (2-hydroxy-3-prenyl-1,4-naphthoquinone) that was found to be active against the Walker-256 carcinoma and Yoshida sarcoma. In the present study, we examined the effect of polyamine (PA)-conjugated derivatives of lapachol, nor-lapachol and lawsone on the growth and invasion of the human GBM cells. The conjugation with PA (a spermidine analog) resulted in dose-dependent and time-dependent increase of cytotoxicity of the 1,4-NQs. In addition, in-vitro inhibition of GBM cell invasion by lapachol was increased upon PA conjugation. Previous biochemical experiments indicated that these PA-1,4-NQs are capable of inhibiting DNA human topoisomerase II-α (topo2α), a major enzyme involved in maintaining DNA topology. Herein, we applied molecular docking to investigate the binding of PA-1,4-NQs to the ATPase site of topo2α. The most active molecules preferentially bind at the ATP-binding site of topo2α, which is energetically favored by the conjugation with PA. Taken together, these findings suggested that the PA-1,4-NQ conjugates might represent potential molecules in the development of new drugs in chemotherapy for malignant brain tumors.
Beyond topoisomerase inhibition: Antitumor 1,4-naphthoquinones as potential inhibitors of human monoamine oxidase
Coelho-Cerqueira, Eduardo,Netz, Paulo A.,Do Canto, Vanessa P.,Pinto, Angelo C.,Follmer, Cristian
, p. 401 - 410 (2014/05/06)
Monoamine oxidase (MAO) action has been involved in the regulation of neurotransmitters levels, cell signaling, cellular growth, and differentiation as well as in the balance of the intracellular polyamine levels. Although so far obscure, MAO inhibitors are believed to have some effect on tumors progression. 1,4-naphthoquinone (1,4-NQ) has been pointed out as a potential pharmacophore for inhibition of both MAO and DNA topoisomerase activities, this latter associated with antitumor activity. Herein, we demonstrated that certain antitumor 1,4-NQs, including spermidine-1,4-NQ, lapachol, and nor-lapachol display inhibitory activity on human MAO-A and MAO-B. Kinetic studies indicated that these compounds are reversible and competitive MAO inhibitors, being the enzyme selectivity greatly affected by substitutions on 1,4-NQ ring. Molecular docking studies suggested that the most potent MAO inhibitors are capable to bind to the MAO active site in close proximity of flavin moiety. Furthermore, ability to inhibit both MAO-A and MAO-B can be potentialized by the formation of hydrogen bonds between these compounds and FAD and/or the residues in the active site. Although spermidine-1,4-NQs exhibit antitumor action primarily by inhibiting topoisomerase via DNA intercalation, our findings suggest that their effect on MAO activity should be taken into account when their application in cancer therapy is considered. Antitumor spermidine-1,4-naphthoquinones are reversible and competitive MAO inhibitors. Spermidine-1,4-NQs that act as potent inhibitors of MAO are capable of binding to FAD moiety. The application of spermidine-1,4-naphthoquinones in cancer therapy should consider their effect on MAO activity.
