17241-45-1

Upstream product

• 186581-53-3 diazomethane 
• 84-79-7 Lapachol 
• 74-88-4 methyl iodide 
• 2348-82-5 2-methoxy-1,4-naphthoquinone 
• 870-63-3 prenyl bromide 
• 104108-29-4 prenyl tributylstannane 
• 57093-27-3 2-(tetra-O-acetyl-β-D-glucopyranosyloxy)-3-(3-methylbut-2-enyl)-1,4-naphthoquinone 
• 77-78-1 dimethyl sulfate 
• 83-72-7 2-hydroxynaphtho-1,4-quinone 
• 684-93-5 1-methyl-1-nitrosourea 

Downstream Products

• 4707-32-8 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione 
• 84-79-7 Lapachol 

Relevant academic research and scientific papers

Inhibition of Staphylococcus aureus TetK and MsrA efflux pumps by hydroxyamines derived from lapachol and norlachol

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.

In silico evaluation of the antibacterial and modulatory activity of lapachol and nor-lapachol derivates

The aim of this research was to investigate the pharmacological properties of 2-(2-hydroxyethylamine)-3-(3-methyl-2-butenyl)-1,4-dihydro-1,4-naphthalenedione, 2-(2-hydroxy-ethylamine)-3-(2-methyl-propenyl)-[1,4]naphthoquinone and 2-(3-hydroxy-propylamine)-3-(3-methyl-2-butenyl)-[1,4]naphthoquinone using computational prediction models, in addition to evaluating the in vitro antibacterial and modulatory activity of these compounds against bacterial ATCC strains and clinical isolates. 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, these then reacted chemoselectively with 2-ethanolamine and 3-propanolamine to form the corresponding amino alcohols. The antibacterial activity and modulatory activity of the substances were assayed by broth microdilution method to determine the Minimum Inhibitory Concentration (MIC). The molecular structures were analyzed using the ChEMBL database to predict possible pharmacological targets, which pointed to the molecule 2- (2-hydroxy-ethylamine)-3-(2-methyl-propenyl)-[1,4]naphthoquinone as a probable antibacterial agent for the proteins Replicative DNA helicase and RecA. The compounds had a low molecular weight and a small number of rotatable bonds. The MICs of the substances were not clinically significant, however, the association with gentamicin and amikacin reduced the MICs of these antibiotics. In conclusion, the combination of these substances with aminoglycosides may be a therapeutic alternative to bacterial resistance and the reduction of side effects.

Secondary amines and unexpected 1-aza-anthraquinones from 2-methoxylapachol

A series of 1-aza-anthraquinones were characterized, besides the expected N-alkylamino derivatives, from the substitution reactions of 2-methoxylapachol with primary amines. An investigation of the reaction conditions allowed reasonable selectivity in the products distribution.

Conjugation with polyamines enhances the antitumor activity of naphthoquinones against human glioblastoma cells

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.

New strategies for molecular diversification of 2-[Aminoalkyl-(1H-1,2,3-Triazol-1- yl)]-1,4-naphthoquinones using click chemistry

Click chemistry-based strategies for the synthesis of 2-Amino-Alkyl-1,2,3-Triazole-1,4- naphthoquinone derivatives make it possible to obtain desired products from 1,4-naphthoquinone (1,4-NQ), and bio-based lawsone, nor-lapachol and lapachol. The first route (Strategy A) starting from 1,4-NQ and amino alcohols, then 2-Amino-Alkyl-1,4-NQ alcohols, were tosylated. The azide ion displaced the tosylate group to afford 2-Azide-Alkyl-1,4-NQ, which was submitted to a copper-catalyzed azide alkyne cycloaddition (CuAAC) condition. The triazole-naphthoquinones were obtained in an overall yield of roughly 47percent. Another pathway (Strategy B) substituted bromo-Alkyl-phthalimides using NaN3 as the nucleophile, sequential CuAAC and deprotection of phthalimide group with hydrazine producing amino-Triazoles. The subsequent reaction with 1,4-NQ produced 2-Amino-Alkyl-1,2,3-Triazole-1,4-NQ derivatives in an overall yield of 45-76percent in four steps. After we developed these two strategies, linear synthesis (Strategy A) was chosen to prepare 2-[(2-(1H-1,2,3-Triazol-1-yl)ethylamino)]-3-(3-methylpropenyl)-1,4-naphthoquinones from lawsone with an overall yield of approximately 27percent in six steps. On the other hand, convergent synthesis (Strategy B) was employed for the synthesis of 2-[(4-phenyl-1H-1,2,3-Triazol-1-yl)alkyl-Amino)]-3-(3-methylbut-2-en-1-yl)-1,4-naphthoquinones from the reaction between 2-methoxy-lapachol with amino-Triazoles with a global yield of about 21percent. These synthetic strategies might lead us to new opportunities to build small-molecule libraries for future biological exploration.

Growth inhibitory activity for cancer cell lines of lapachol and its natural and semi-synthetic derivatives

A series of 17 selected natural and semisynthetic 1,4-naphthoquinones were synthesized, and their growth inhibitory activity was evaluated in vitro. The compounds were tested on six human cancer cell lines using the MTT colorimetric assay. The data revealed that of the chemicals under study only lapachol, its acetate and 3-geranyllawsone displayed the highest activity, recording mean IC50 values ranging from 15 to 22 μM.

Beyond topoisomerase inhibition: Antitumor 1,4-naphthoquinones as potential inhibitors of human monoamine oxidase

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.

A mechanistic study on the Hooker oxidation: Synthesis of novel indane carboxylic acid derivatives from lapachol

The Hooker oxidation is one of the most intriguing transformations wherein lapachol (1) is readily converted to norlapachol (2) in very good yield. This one-pot reaction involves a very intricate mechanism in which the alkyl side chain of lapachol is shortened by one carbon unit. Previous studies have unequivocally established the involvement of an indane carboxylic acid derivative 3, as a key intermediate (Hooker intermediate), and its simultaneous conversion to norlapachol (2) via the oxidative cleavage of vicinol diol and subsequent intramolecular aldol reaction of the resulting keto acid. However, the formation of the key Hooker intermediate 3 from lapachol (1) remains ambiguous. The present study has thrown some light on the formation of the key intermediate 3 from lapachol (1) via benzilic acid rearrangement of the corresponding labile o-diquinone intermediate 8 derived from lapachol. The involvement of o-diquinone intermediate 8 in the Hooker oxidation has been further established by trapping of this labile intermediate as the corresponding phenazine derivative 9. The involvement of benzilic acid rearrangement as a key step in the Hooker oxidation is further shown with a variety of o-quinones prepared from lapachol (1). The Royal Society of Chemistry 2013.

Synthesis of lapachol derivatives and their antibacterial activity

Several lapachol derivatives were synthesized from lapachol and tested for their antibacterial activity.

Trypanocidal activity of synthetic heterocyclic derivatives of active quinones from Tabebuia sp.

Continuing a program on the chemistry and biological activity of compounds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl derivatives of lawsone, a natural quinone from Lausonia alba inactive against T. cruzi, is reported. The introduction of an allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activity against the parasite, with ID50 values of 420.7 ± 71.1 and 330.7 ± 62.4 μmol/l, respectively. The trypanocidal activity of the naphtho cyclics synthesized from the original quinones showed no concordant behavior in relation to the parent compound. Six of nine of the synthesized compounds presented lower ID50 values than crystal violet, indicating a general trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type. However, their chemical structures do not endow them with the capacity of free radical generation by biological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benzidazole, responsible for such behaviour. As a hypothesis, the pattern of their biological actions should be focused in other aspects of their chemical structures. Because of their polycyclic planar topology, these derivatives are potential candidates for experimental tests as DNA intercalating agents.