Effect of Scopoletin on Erthrocyte Membrane Ion Motive Atpases

Ezeokonkwo, C. A.; Obidoa, Onyechi

doi:10.4314/njnpm.v5i1.11721

Cited by 4 publications

(3 citation statements)

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“…The reported pharmacological effects of scopoletin presuppose some interactions with membrane-bound enzymes, such as Ca 2+ -ATPase, which is vital in nervous signal conduction [ 33 , 34 , 35 ]. Oliveira [ 36 ] reported that in rats, scopoletin inhibits Ca 2+ -ATPase activity by inhibiting the mobilization of intracellular calcium from noradrenaline-sensitive Ca stores.…”

Section: Discussionmentioning

confidence: 99%

3D-QSAR and Molecular Docking Studies on the TcPMCA1-Mediated Detoxification of Scopoletin and Coumarin Derivatives

Hou

Luo

Zhang

et al. 2017

IJMS

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The carmine spider mite, Tetranychus cinnabarinus (Boisduval), is an economically important agricultural pest that is difficult to prevent and control. Scopoletin is a botanical coumarin derivative that targets Ca2+-ATPase to exert a strong acaricidal effect on carmine spider mites. In this study, the full-length cDNA sequence of a plasma membrane Ca2+-ATPase 1 gene (TcPMCA1) was cloned. The sequence contains an open reading frame of 3750 bp and encodes a putative protein of 1249 amino acids. The effects of scopoletin on TcPMCA1 expression were investigated. TcPMCA1 was significantly upregulated after it was exposed to 10%, 30%, and 50% of the lethal concentration of scopoletin. Homology modeling, molecular docking, and three-dimensional quantitative structure-activity relationships were then studied to explore the relationship between scopoletin structure and TcPMCA1-inhibiting activity of scopoletin and other 30 coumarin derivatives. Results showed that scopoletin inserts into the binding cavity and interacts with amino acid residues at the binding site of the TcPMCA1 protein through the driving forces of hydrogen bonds. Furthermore, CoMFA (comparative molecular field analysis)- and CoMSIA (comparative molecular similarity index analysis)-derived models showed that the steric and H-bond fields of these compounds exert important influences on the activities of the coumarin compounds.Notably, the C3, C6, and C7 positions in the skeletal structure of the coumarins are the most suitable active sites. This work provides insights into the mechanism underlying the interaction of scopoletin with TcPMCA1. The present results can improve the understanding on plasma membrane Ca2+-ATPase-mediated (PMCA-mediated) detoxification of scopoletin and coumarin derivatives in T. cinnabarinus, as well as provide valuable information for the design of novel PMCA-inhibiting acaricides.

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Section: Discussionmentioning

confidence: 99%

3D-QSAR and Molecular Docking Studies on the TcPMCA1-Mediated Detoxification of Scopoletin and Coumarin Derivatives

Hou

Luo

Zhang

et al. 2017

IJMS

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“…In uninfected erythrocytes internal Na concentration is much lower than external concentration, but the K concentration is higher; in infected blood cells this situation is drastically reversed [103] . Scopoletin significantly stimulated erythrocyte membrane ATPases at 0.1 µmol/L, in particular Na-K-ATPase vs Ca-ATPase or Mg-ATPase [104] , so scopoletin may affect malaria infection. A significant hormetic effect was also noticed; stimulation was higher at scopoletin concentrations of 10 µg/mL than at 1 or at 100 µg/mL.…”

Section: Non-artemisinin Therapeutic Compounds In a Annuamentioning

confidence: 99%

Dried-leafArtemisia annua: A practical malaria therapeutic for developing countries?

Weathers

Towler

Hassanali

et al. 2014

WJP

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Artemisinin from the plant Artemisia annua (A. annua) L, and used as artemisinin combination therapy (ACT), is the current best therapeutic for treating malaria, a disease that hits children and adults especially in developing countries. Traditionally, A. annua was used by the Chinese as a tea to treat "fever". More recently, investigators have shown that tea infusions and oral consumption of the dried leaves of the plant have prophylactic and therapeutic efficacy. The presence of a complex matrix of chemicals within the leaves seems to enhance both the bioavailability and efficacy of artemisinin. Although about 1000-fold less potent than artemisinin in their antiplasmodial activity, these plant chemicals are mainly small molecules that include other artemisinic compounds, terpenes (mainly mono and sesqui), flavonoids, and polyphenolic acids. In addition, polysaccharide constituents of A. annua may enhance bioavailability of artemisinin. Rodent pharmacokinetics showed longer T 1/2 and T max and greater C max and AUC in Plasmodium chabaudi-infected mice treated with A. annua dried leaves than in healthy mice. Pharmacokinetics of deoxyartemisinin, a liver metabolite of artemisinin, was more inhibited in infected than in healthy mice. In healthy mice, artemisinin serum levels were > 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. Human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure

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“…Studies have shown that scopoletin has a wide spectrum of biological activities, such as pronounced acaricidal [ 23 , 24 ], anti-inflammatory [ 25 , 26 ], antitumoral [ 27 ], antioxidative [ 20 ], hepatoprotective [ 28 ], insecticidal [ 29 ], antifungal [ 30 ], and alleopathic properties [ 31 ]. Based on its pronounced acaricidal activities, our research group further investigated the mechanism of action and found that Ca 2+ -ATPase, which is vital in nervous signal conduction [ 32 , 33 , 34 ], was inhibited [ 35 ] and TcPMCA1 from Ca 2+ -ATPase was significantly upregulated after T. cinnabarlnus was exposed to scopoletin, and molecular docking also showed that scopoletin inserts into the binding cavity and interacts with TcPMCA1 protein through the driving forces of hydrogen bonds [ 36 ]. However, its acaricidal activity remain lower than that of some registered synthetic chemical acaricides, such as pyridaben.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions

et al. 2018

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Thirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduval) were evaluated using the slide-dip method. The results indicated that some of these compounds exhibit more pronounced acaricidal activity than scopoletin, especially compounds 32, 20, 28, 27 and 8 which exhibited about 8.41-, 7.32-, 7.23-, 6.76-, and 6.65-fold higher acaricidal potency. Compound 32 possessed the the most promising acaricidal activity and exhibited about 1.45-fold higher acaricidal potency against T. cinnabarinus than propargite. Statistically significant 2D-QSAR model supports the observed acaricidal activities and reveals that polarizability (HATS5p) was the most important parameter controlling bioactivity. 3D-QSAR (CoMFA: q2 = 0.802, r2 = 0.993; CoMSIA: q2 = 0.735, r2 = 0.965) results show that bulky substituents at R4, R1, R2 and R5 (C6, C3, C4, and C7) positions, electron positive groups at R5 (C7) position, hydrophobic groups at R1 (C3) and R2 (C4), H-bond donors groups at R1 (C3) and R4 (C6) will increase their acaricidal activity, which provide a good insight into the molecular features relevant to the acaricidal activity for further designing novel acaricidal agents. Molecular docking demonstrates that these selected derivatives display different bide modes with TcPMCA1 from lead compound and they interact with more key amino acid residues than scopoletin. In silico ADME properties of scopoletin and its phenolic ether derivatives were also analyzed and showed potential to develop as good acaricidal candidates.

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Effect of Scopoletin on Erthrocyte Membrane Ion Motive Atpases

Cited by 4 publications

References 0 publications

3D-QSAR and Molecular Docking Studies on the TcPMCA1-Mediated Detoxification of Scopoletin and Coumarin Derivatives

3D-QSAR and Molecular Docking Studies on the TcPMCA1-Mediated Detoxification of Scopoletin and Coumarin Derivatives

Dried-leafArtemisia annua: A practical malaria therapeutic for developing countries?

Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions

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