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Molecular docking studies of anti-cancerous candidates in Hippophae rhamnoides and Hippophae salicifolia.

Usha T, Middha SK, Goyal AK, Karthik M, Manoj D, Faizan S, Goyal P, Prashanth H, Pande V - J Biomed Res (2014)

Bottom Line: Docking studies revealed that four compounds, isorhamnetin-7-rhamnoside, quercetin-3-glucoside-7-rhamnoside (present in H. rhamnoides), zeaxanthin, and translutein (present in H. salicifolia) significantly bind with binding energies -17.1534, -14.7936, -10.2105 and -17.2217 Kcal/mol, respectively, even though they slightly deviate from Lipinski's rule.Absorption, distribution, metabolism, excretion and toxicity (ADME/tox) analyses of these compounds and their stereoisomers showed that they were less toxic and non-mutagenic.Amongst them, isorhamntein-7-rhamnoside showed hepatotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biotechnology, Maharani Lakshmi Ammanni College For Women, Bangalore, India.

ABSTRACT
Actinorhizal plants contain numerous antioxidants that may play a crucial role in preventing the formation of tumors. H-Ras p21, a member of the Ras-GTPase family, is a promising target to treat various kinds of cancers. An in silico docking study was carried out to identify the inhibitory potential of compounds of these plants against H-Ras by using Discovery Studio 3.5 and by using Autodock 4.2. Docking studies revealed that four compounds, isorhamnetin-7-rhamnoside, quercetin-3-glucoside-7-rhamnoside (present in H. rhamnoides), zeaxanthin, and translutein (present in H. salicifolia) significantly bind with binding energies -17.1534, -14.7936, -10.2105 and -17.2217 Kcal/mol, respectively, even though they slightly deviate from Lipinski's rule. Absorption, distribution, metabolism, excretion and toxicity (ADME/tox) analyses of these compounds and their stereoisomers showed that they were less toxic and non-mutagenic. Amongst them, isorhamntein-7-rhamnoside showed hepatotoxicity. Hence, these compounds can be further investigated in vivo to optimize their formulation and concentration and to develop potential chemical entities for the prevention and treatment of cancers.

No MeSH data available.


Related in: MedlinePlus

Prediction of drug absorption for various compounds.A: translutein B: zeaxanthin C: isorhamnetin 7-rhamnoside, D: quercetin 3-glucoside-7-rhamnoside, a: lutein stereoisomer, b: isorhamnetin (pure) and c: quercetin (pure) [x axis indicates the solubility of the compounds; y axis indicates the log P values] considered using Discovery Studio 2.1 (Accelrys, San Diego, CA). ADMET Descriptors, 2D polar surface area (PSA_2D) in Å2 for each compound is plotted against their corresponding calculated atom-type partition coefficient (ALogP98). The area covered by the ellipse is a prophecy of excellent absorption without any violation of ADMET properties. Ellipses indicate the absorption model at 95% and 99% confidence limit to the blood brain barrier (BBB) and intestinal absorption models.
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f05: Prediction of drug absorption for various compounds.A: translutein B: zeaxanthin C: isorhamnetin 7-rhamnoside, D: quercetin 3-glucoside-7-rhamnoside, a: lutein stereoisomer, b: isorhamnetin (pure) and c: quercetin (pure) [x axis indicates the solubility of the compounds; y axis indicates the log P values] considered using Discovery Studio 2.1 (Accelrys, San Diego, CA). ADMET Descriptors, 2D polar surface area (PSA_2D) in Å2 for each compound is plotted against their corresponding calculated atom-type partition coefficient (ALogP98). The area covered by the ellipse is a prophecy of excellent absorption without any violation of ADMET properties. Ellipses indicate the absorption model at 95% and 99% confidence limit to the blood brain barrier (BBB) and intestinal absorption models.

Mentions: Fig. 4 depicts that all the compounds have poor intestinal absorption levels and may prove to be toxic. All the compounds except isorhamnetin and quercetin in their pure forms exhibited mutagenicity as predicted by TOPKAT Ames mutagenicity test of DS. Vitamin C being naturally present in the human body proves to be easily soluble in the intestine. As a result, to increase the safety and efficacy of the ligand molecules, the stereoisomers and pure forms of the drugs obtained from PubChem were also checked for their ADMET properties. As shown in Fig. 5, the stereoisomers have shown better intestinal absorption, since they lie in 99% confidence ellipses in comparison to the ligand forms available in herbs. As shown in Table 4, zeaxanthin in both forms exhibited the same pharmacological properties. Lutein, a stereoisomer of translutein is more toxic because of high penetrance through BBB. Table 4 also represents that the pure forms of isorhamnetin and quercetin show better absorption.


Molecular docking studies of anti-cancerous candidates in Hippophae rhamnoides and Hippophae salicifolia.

Usha T, Middha SK, Goyal AK, Karthik M, Manoj D, Faizan S, Goyal P, Prashanth H, Pande V - J Biomed Res (2014)

Prediction of drug absorption for various compounds.A: translutein B: zeaxanthin C: isorhamnetin 7-rhamnoside, D: quercetin 3-glucoside-7-rhamnoside, a: lutein stereoisomer, b: isorhamnetin (pure) and c: quercetin (pure) [x axis indicates the solubility of the compounds; y axis indicates the log P values] considered using Discovery Studio 2.1 (Accelrys, San Diego, CA). ADMET Descriptors, 2D polar surface area (PSA_2D) in Å2 for each compound is plotted against their corresponding calculated atom-type partition coefficient (ALogP98). The area covered by the ellipse is a prophecy of excellent absorption without any violation of ADMET properties. Ellipses indicate the absorption model at 95% and 99% confidence limit to the blood brain barrier (BBB) and intestinal absorption models.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4197392&req=5

f05: Prediction of drug absorption for various compounds.A: translutein B: zeaxanthin C: isorhamnetin 7-rhamnoside, D: quercetin 3-glucoside-7-rhamnoside, a: lutein stereoisomer, b: isorhamnetin (pure) and c: quercetin (pure) [x axis indicates the solubility of the compounds; y axis indicates the log P values] considered using Discovery Studio 2.1 (Accelrys, San Diego, CA). ADMET Descriptors, 2D polar surface area (PSA_2D) in Å2 for each compound is plotted against their corresponding calculated atom-type partition coefficient (ALogP98). The area covered by the ellipse is a prophecy of excellent absorption without any violation of ADMET properties. Ellipses indicate the absorption model at 95% and 99% confidence limit to the blood brain barrier (BBB) and intestinal absorption models.
Mentions: Fig. 4 depicts that all the compounds have poor intestinal absorption levels and may prove to be toxic. All the compounds except isorhamnetin and quercetin in their pure forms exhibited mutagenicity as predicted by TOPKAT Ames mutagenicity test of DS. Vitamin C being naturally present in the human body proves to be easily soluble in the intestine. As a result, to increase the safety and efficacy of the ligand molecules, the stereoisomers and pure forms of the drugs obtained from PubChem were also checked for their ADMET properties. As shown in Fig. 5, the stereoisomers have shown better intestinal absorption, since they lie in 99% confidence ellipses in comparison to the ligand forms available in herbs. As shown in Table 4, zeaxanthin in both forms exhibited the same pharmacological properties. Lutein, a stereoisomer of translutein is more toxic because of high penetrance through BBB. Table 4 also represents that the pure forms of isorhamnetin and quercetin show better absorption.

Bottom Line: Docking studies revealed that four compounds, isorhamnetin-7-rhamnoside, quercetin-3-glucoside-7-rhamnoside (present in H. rhamnoides), zeaxanthin, and translutein (present in H. salicifolia) significantly bind with binding energies -17.1534, -14.7936, -10.2105 and -17.2217 Kcal/mol, respectively, even though they slightly deviate from Lipinski's rule.Absorption, distribution, metabolism, excretion and toxicity (ADME/tox) analyses of these compounds and their stereoisomers showed that they were less toxic and non-mutagenic.Amongst them, isorhamntein-7-rhamnoside showed hepatotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biotechnology, Maharani Lakshmi Ammanni College For Women, Bangalore, India.

ABSTRACT
Actinorhizal plants contain numerous antioxidants that may play a crucial role in preventing the formation of tumors. H-Ras p21, a member of the Ras-GTPase family, is a promising target to treat various kinds of cancers. An in silico docking study was carried out to identify the inhibitory potential of compounds of these plants against H-Ras by using Discovery Studio 3.5 and by using Autodock 4.2. Docking studies revealed that four compounds, isorhamnetin-7-rhamnoside, quercetin-3-glucoside-7-rhamnoside (present in H. rhamnoides), zeaxanthin, and translutein (present in H. salicifolia) significantly bind with binding energies -17.1534, -14.7936, -10.2105 and -17.2217 Kcal/mol, respectively, even though they slightly deviate from Lipinski's rule. Absorption, distribution, metabolism, excretion and toxicity (ADME/tox) analyses of these compounds and their stereoisomers showed that they were less toxic and non-mutagenic. Amongst them, isorhamntein-7-rhamnoside showed hepatotoxicity. Hence, these compounds can be further investigated in vivo to optimize their formulation and concentration and to develop potential chemical entities for the prevention and treatment of cancers.

No MeSH data available.


Related in: MedlinePlus