β-Lapachone: A naphthoquinone with promising antischistosomal properties in mice

Aires, André de Lima; Ximenes, Eulália Camelo Pessoa Azevedo; Barbosa, Vanessa Xavier; Góes, Alexandre José da Silva; Souza, Valdênia Maria Oliveira de; Albuquerque, Mônica Camelo Pessôa de Azevedo

doi:10.1016/j.phymed.2013.08.012

Cited by 34 publications

(18 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to our work, other studies of schistosomicidal activity have reported on similar or higher reductions in the number of adult worms and eggs (Abdulla et al, 2007;Allan et al, 2009;Aires et al, 2014). The results obtained with the three doses of DNK administered to mice did not evidence any significant correlation between dose and response, probably because the pharmacokinetic parameters can be involved with the lack of correlation between dose and response.…”

Section: Discussioncontrasting

confidence: 54%

See 1 more Smart Citation

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

et al. 2015

View full text Add to dashboard Cite

The chemotherapy of schistosomiasis relies on the use of praziquantel. However, concerns over drug resistance have encouraged the search for new drug leads. This paper is the first report on the in vitro and in vivo activity of (-)-6,6'-dinitrohinokinin (DNK) against Schistosoma mansoni. In vitro, the lethal concentrations for 50% of parasites (LC50) of DNK against adult worms were 103.9±3.6 and 102.5±4.8μM at 24 and 72h, respectively. Scanning electron microscopy images showed extensive tegumental alterations such as peeling and smaller numbers of tubercles in the spine of adult worms. DNK also elicited high mortality of schistosomula, with LC50 values of 57.4±2.3, 32.5±0.9, and 20.4±1.2μM at 24, 48, and 72h, respectively. DNK displayed moderate activity against the juvenile liver parasite, with an LC50 value of 179.5±2.3 μM at 72h. This compound reduced the total number of eggs by over 83%, and it affected the development of eggs produced by adult worms. The selectivity index showed that at 24h, DNK was 8.5 and 15.4 times more toxic to the adult worms and schistosomula than to Chinese hamster lung fibroblast cells, respectively. Treatment of infected mice with DNK moderately decreased worm burden (33.8-52.3%), egg production (40.7-60.0%), and spleen and liver weights. Together, our results indicated that DNK presents moderate in vitro and in vivo activities against S. mansoni, and it might therefore be interesting to explore the structure-activity relationship of the antischistosomal activity of this compound.

show abstract

Section: Discussioncontrasting

confidence: 54%

“…The applied administration protocol was that suggested by the WHO for a primary in vivo screening study (Ramirez et al, 2007) and by other investigations (Abdulla et al, 2007;Sayed et al 2008;Allan et al, 2009;Aires et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Similar effects on oogram were described with treatment of infected animals with dexamethasone (50 mg/kg) [34]. In addition, Aires et al [35] observed eggs in all development phases following administration of β-lapachone, however the percentage of immature eggs was significant lower, indicating a kinetic change in the egg development.…”

Section: Discussionsupporting

confidence: 60%

In vivo and In vitro of Arctiin Schistosomicidal Activity

LC¹,

MM²,

PM³

et al. 2017

Clin Exp Pharmacol

View full text Add to dashboard Cite

Human schistosomiasis, caused by trematode worms of the genus Schistosoma, is one of the most significant neglected tropical diseases, affecting more 200 million individuals worldwide and praziquantel is the only available drug to treat this neglected disease. Arctiin is a lignan obtained from Arctium lappa (Asteraceae) with antiinflammatory and antiproliferative activities. Our purpose was to investigate the in vitro and in vivo schistosomicidal activities of arctiin in mice infected with S. mansoni. Arctiin (200 and 100 μM) caused mortality, tegumental alterations, and reduction of motor activity of adult worms of S. mansoni in culture. Oral administration of a single dose of arctiin (25 mg/kg) on day 45 of infection did not reduce worm burden or cause any alteration in the analyzed parameters when compared to infected untreated mice. On the other hand, intraperitoneal treatment with arctiin (50 mg/kg) was able to reduce the hepatic granuloma volume by 20% in comparison to infected untreated mice. In addition, after intraperitoneal administration of arctiin in mice it was shown by HPLC analysis that arctiin was present in murine plasma. More studies should be conducted to verify the possible mechanism of action on inflammatory components present in granuloma formation.

show abstract

“…β‐lapachone (3,4‐dihydro‐2,2‐dimethyl‐2H‐naphthol‐[1,2‐b]pyran‐5,6‐dione) is a naphthoquinone derived from the lapachol, which is isolated from the bark of the Tabebuia avellanedae , a tree native to South America . β‐lapachone (β‐lap) presents several pharmacological properties including antineoplastic activity . The mechanism of action of the β‐lap involves an increased generation of reactive oxygen species, inducing extensive DNA damage, H2AX phosphorylation, and Poly (ADP ribose) polymerase hyperactivation culminating in apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular interactions between β‐lapachone with cyclodextrins studied using isothermal titration calorimetry and molecular modeling

Xavier

Rabello

Hernandes

et al. 2017

J of Molecular Recognition

View full text Add to dashboard Cite

Supramolecular interactions between β-lapachone (β-lap) and cyclodextrins (CDs) were investigated by isothermal titration calorimetry. The most favorable host: guest interaction was characterized using X-ray powder diffraction (XRD), differential scanning calorimetry and thermogravimetry (DSC/TG), spectroscopy (FT-IR), spectroscopy (2D ROESY) nuclear magnetic resonance (NMR), and molecular modeling. Phase solubility diagrams showed β-, HP-β-, SBE-β-, γ-, and HP-γ-CDs at 1.5% (w/w) allowed an increase in apparent solubility of β-lap with enhancement factors of 12.0, 10.1, 11.8, 2.4, and 2.2, respectively. β-lap has a weak interaction with γ- and HP-γ-CDs and tends to interact more favorably with β-CD and its derivatives, especially SBE-β-CD (K = 4160 M ; ΔG = -20.66 kJ·mol ). Thermodynamic analysis suggests a hydrophobic interaction associated with the displacement of water from the cavity of the CD by the β-lap. In addition, van der Waals forces and hydrogen bonds were responsible for the formation of complexes. Taken together, the results showed intermolecular interactions between β-lap and SBE-β-CD, thereby confirming the formation of the inclusion complex. Molecular docking results showed 2 main orientations in which the interaction of benzene moiety at the wider rim of the SBE-β-CD is the most stable (average docking energy of -7.0 kcal/mol). In conclusion, β-lap:SBE-β-CD is proposed as an approach for use in drug delivery systems in cancer research.

show abstract

β-Lapachone: A naphthoquinone with promising antischistosomal properties in mice

Cited by 34 publications

References 61 publications

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

In vivo and In vitro of Arctiin Schistosomicidal Activity

Supramolecular interactions between β‐lapachone with cyclodextrins studied using isothermal titration calorimetry and molecular modeling

Contact Info

Product

Resources

About