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In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin.

Ntie-Kang F, Lifongo LL, Mbah JA, Owono Owono LC, Megnassan E, Mbaze LM, Judson PN, Sippl W, Efange SM - In Silico Pharmacol (2013)

Bottom Line: Material from some of the plant sources are currently employed in African Traditional Medicine.This survey demonstrated that about 45% of the compounds within the ConMedNP compound library are compliant, having properties which fall within the range of ADME properties of 95% of currently known drugs, while about 69% of the compounds have ≤ 2 violations.Moreover, about 73% of the compounds within the corresponding "drug-like" subset showed compliance.

View Article: PubMed Central - PubMed

Affiliation: CEPAMOQ, Faculty of Science, University of Douala, P.O. Box 8580, Douala, Cameroon ; Chemical and Bioactivity Information Centre, Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon ; Department of Pharmaceutical Sciences, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck Str. 4, 06120 Halle (Saale), Germany.

ABSTRACT

Purpose: Drug metabolism and pharmacokinetics (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. The use of computer modelling to predict the DMPK and toxicity properties of a natural product library derived from medicinal plants from Central Africa (named ConMedNP). Material from some of the plant sources are currently employed in African Traditional Medicine.

Methods: Computer-based methods are slowly gaining ground in this area and are often used as preliminary criteria for the elimination of compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of discovery of a drug. In the present study, we present an in silico assessment of the DMPK and toxicity profile of a natural product library containing ~3,200 compounds, derived from 379 species of medicinal plants from 10 countries in the Congo Basin forests and savannas, which have been published in the literature. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination and toxicity (ADMET) of the compounds.

Results: This survey demonstrated that about 45% of the compounds within the ConMedNP compound library are compliant, having properties which fall within the range of ADME properties of 95% of currently known drugs, while about 69% of the compounds have ≤ 2 violations. Moreover, about 73% of the compounds within the corresponding "drug-like" subset showed compliance.

Conclusions: In addition to the verified levels of "drug-likeness", diversity and the wide range of measured biological activities, the compounds from medicinal plants in Central Africa show interesting DMPK profiles and hence could represent an important starting point for hit/lead discovery.

No MeSH data available.


Related in: MedlinePlus

Graphs showing the distribution of the predicted number of metabolic reactions for compounds in ConMedNP. Colour codes are as defined in Figure 1.
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Fig7: Graphs showing the distribution of the predicted number of metabolic reactions for compounds in ConMedNP. Colour codes are as defined in Figure 1.

Mentions: An estimated number of possible metabolic reactions has also been predicted by QikProp and used to determine whether the molecules can easily gain access to the target site after entering the blood stream. The average estimated number of possible metabolic reactions for the ConMedNP library is between 5 and 6, while those of the standard subsets are respectively between 4 and 5, between 3 and 4 and between 1 and 2 for the “drug-like”, “lead-like” and “fragment-like” libraries (Table 2). Even though some of the compounds are likely to undergo as many as up to 26 metabolic reactions due to the complexity of some of the plant secondary metabolites within the database (Figure 7), ~81% of the compounds are predicted to undergo the recommended number of metabolic steps (1 to 8 reactions), with the situation improving to ~92% and almost 100% in the “drug-like” and “lead-like” subsets respectively. From Figure 7, it can be observed that the total and “lead-like” libraries show peak values at 3 metabolic steps, while the drug-like subset rather shows a peak at 4 metabolic steps and the “fragment-like” subsets peaks at 2 predicted metabolic reactions.Figure 7


In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin.

Ntie-Kang F, Lifongo LL, Mbah JA, Owono Owono LC, Megnassan E, Mbaze LM, Judson PN, Sippl W, Efange SM - In Silico Pharmacol (2013)

Graphs showing the distribution of the predicted number of metabolic reactions for compounds in ConMedNP. Colour codes are as defined in Figure 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230438&req=5

Fig7: Graphs showing the distribution of the predicted number of metabolic reactions for compounds in ConMedNP. Colour codes are as defined in Figure 1.
Mentions: An estimated number of possible metabolic reactions has also been predicted by QikProp and used to determine whether the molecules can easily gain access to the target site after entering the blood stream. The average estimated number of possible metabolic reactions for the ConMedNP library is between 5 and 6, while those of the standard subsets are respectively between 4 and 5, between 3 and 4 and between 1 and 2 for the “drug-like”, “lead-like” and “fragment-like” libraries (Table 2). Even though some of the compounds are likely to undergo as many as up to 26 metabolic reactions due to the complexity of some of the plant secondary metabolites within the database (Figure 7), ~81% of the compounds are predicted to undergo the recommended number of metabolic steps (1 to 8 reactions), with the situation improving to ~92% and almost 100% in the “drug-like” and “lead-like” subsets respectively. From Figure 7, it can be observed that the total and “lead-like” libraries show peak values at 3 metabolic steps, while the drug-like subset rather shows a peak at 4 metabolic steps and the “fragment-like” subsets peaks at 2 predicted metabolic reactions.Figure 7

Bottom Line: Material from some of the plant sources are currently employed in African Traditional Medicine.This survey demonstrated that about 45% of the compounds within the ConMedNP compound library are compliant, having properties which fall within the range of ADME properties of 95% of currently known drugs, while about 69% of the compounds have ≤ 2 violations.Moreover, about 73% of the compounds within the corresponding "drug-like" subset showed compliance.

View Article: PubMed Central - PubMed

Affiliation: CEPAMOQ, Faculty of Science, University of Douala, P.O. Box 8580, Douala, Cameroon ; Chemical and Bioactivity Information Centre, Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon ; Department of Pharmaceutical Sciences, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck Str. 4, 06120 Halle (Saale), Germany.

ABSTRACT

Purpose: Drug metabolism and pharmacokinetics (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. The use of computer modelling to predict the DMPK and toxicity properties of a natural product library derived from medicinal plants from Central Africa (named ConMedNP). Material from some of the plant sources are currently employed in African Traditional Medicine.

Methods: Computer-based methods are slowly gaining ground in this area and are often used as preliminary criteria for the elimination of compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of discovery of a drug. In the present study, we present an in silico assessment of the DMPK and toxicity profile of a natural product library containing ~3,200 compounds, derived from 379 species of medicinal plants from 10 countries in the Congo Basin forests and savannas, which have been published in the literature. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination and toxicity (ADMET) of the compounds.

Results: This survey demonstrated that about 45% of the compounds within the ConMedNP compound library are compliant, having properties which fall within the range of ADME properties of 95% of currently known drugs, while about 69% of the compounds have ≤ 2 violations. Moreover, about 73% of the compounds within the corresponding "drug-like" subset showed compliance.

Conclusions: In addition to the verified levels of "drug-likeness", diversity and the wide range of measured biological activities, the compounds from medicinal plants in Central Africa show interesting DMPK profiles and hence could represent an important starting point for hit/lead discovery.

No MeSH data available.


Related in: MedlinePlus