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Finding needles in a haystack: application of network analysis and target enrichment studies for the identification of potential anti-diabetic phytochemicals.

Fayaz SM, Suvanish Kumar VS, Rajanikant KG - PLoS ONE (2014)

Bottom Line: Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects.This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations.Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

View Article: PubMed Central - PubMed

Affiliation: School of Biotechnology, National Institute of Technology Calicut, Calicut 673601, India.

ABSTRACT
Diabetes mellitus is a debilitating metabolic disorder and remains a significant threat to public health. Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects. However, the complexity in their chemical constituents and mechanism of action, hinder the effort to discover novel anti-diabetic drugs. Hence, understanding the biological and chemical basis of pharmacological action of phytochemicals is essential for the discovery of potential anti-diabetic drugs. Identifying important active compounds, their protein targets and the pathways involved in diabetes would serve this purpose. In this context, the present study was aimed at exploring the mechanism of action of anti-diabetic plants phytochemicals through network and chemical-based approaches. This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations. Further, a protocol for target enrichment was proposed, to identify novel protein targets for important active compounds. Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

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Related in: MedlinePlus

Compounds docked to DNA topoisomerase 2.(A) Betulinic acid, (B) Diadzein, (C) Genistein and (D) Oleanolic acid. Betulinic acid and diadzein bind to this protein with different features. Diadzein and genistein bind with similar features. Oleanolic acid and betulinic acid also bind with similar features.
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pone-0112911-g014: Compounds docked to DNA topoisomerase 2.(A) Betulinic acid, (B) Diadzein, (C) Genistein and (D) Oleanolic acid. Betulinic acid and diadzein bind to this protein with different features. Diadzein and genistein bind with similar features. Oleanolic acid and betulinic acid also bind with similar features.

Mentions: In the case of betulinic acid, the active compound, diadzein, shares the protein target DNA topoisomerase 2 and oleanolic acid shares the protein targets, namely, glycogen phosphorylase, diacylglycerol acyltransferase and DNA polymerase beta. Betulinic acid and diadzein do not have similar pharmacophoric features. Therefore, betulinic acid might not bind to the other targets of diadzein. This was further confirmed through docking of betulinic acid and diadzein to DNA topoisomerase 2. Both these compounds bind to this protein with different features (Figure 14). During pharmacophore analysis, it was observed that among the compounds that bind to DNA topoisomerase 2, diadzein and genistein have similar pharmacophoric features. When these compounds were docked to this protein, it was found that they bind with similar features. This further supports the fact that if two compounds have similar pharmacophoric features, they bind to a common protein target, which could be proved through docking studies.


Finding needles in a haystack: application of network analysis and target enrichment studies for the identification of potential anti-diabetic phytochemicals.

Fayaz SM, Suvanish Kumar VS, Rajanikant KG - PLoS ONE (2014)

Compounds docked to DNA topoisomerase 2.(A) Betulinic acid, (B) Diadzein, (C) Genistein and (D) Oleanolic acid. Betulinic acid and diadzein bind to this protein with different features. Diadzein and genistein bind with similar features. Oleanolic acid and betulinic acid also bind with similar features.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232558&req=5

pone-0112911-g014: Compounds docked to DNA topoisomerase 2.(A) Betulinic acid, (B) Diadzein, (C) Genistein and (D) Oleanolic acid. Betulinic acid and diadzein bind to this protein with different features. Diadzein and genistein bind with similar features. Oleanolic acid and betulinic acid also bind with similar features.
Mentions: In the case of betulinic acid, the active compound, diadzein, shares the protein target DNA topoisomerase 2 and oleanolic acid shares the protein targets, namely, glycogen phosphorylase, diacylglycerol acyltransferase and DNA polymerase beta. Betulinic acid and diadzein do not have similar pharmacophoric features. Therefore, betulinic acid might not bind to the other targets of diadzein. This was further confirmed through docking of betulinic acid and diadzein to DNA topoisomerase 2. Both these compounds bind to this protein with different features (Figure 14). During pharmacophore analysis, it was observed that among the compounds that bind to DNA topoisomerase 2, diadzein and genistein have similar pharmacophoric features. When these compounds were docked to this protein, it was found that they bind with similar features. This further supports the fact that if two compounds have similar pharmacophoric features, they bind to a common protein target, which could be proved through docking studies.

Bottom Line: Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects.This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations.Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

View Article: PubMed Central - PubMed

Affiliation: School of Biotechnology, National Institute of Technology Calicut, Calicut 673601, India.

ABSTRACT
Diabetes mellitus is a debilitating metabolic disorder and remains a significant threat to public health. Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects. However, the complexity in their chemical constituents and mechanism of action, hinder the effort to discover novel anti-diabetic drugs. Hence, understanding the biological and chemical basis of pharmacological action of phytochemicals is essential for the discovery of potential anti-diabetic drugs. Identifying important active compounds, their protein targets and the pathways involved in diabetes would serve this purpose. In this context, the present study was aimed at exploring the mechanism of action of anti-diabetic plants phytochemicals through network and chemical-based approaches. This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations. Further, a protocol for target enrichment was proposed, to identify novel protein targets for important active compounds. Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

Show MeSH
Related in: MedlinePlus