Abstract
PurposeDrug 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.MethodsComputer-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.ResultsThis 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-9616-1-12) contains supplementary material, which is available to authorized users.
Highlights
Natural products (NPs) have always played an important role in drug discovery until today (Li and Vederas 2009; Chin et al 2006; Newman 2008; Harvey 2008; Koehn and Carter 2005)
Overall Drug metabolism and pharmacokinetics (DMPK) compliance of the ConMedNP library The 24 most relevant molecular descriptors calculated by QikProp are used to determine the #star parameter (Schrödinger 2011d)
RSC Adv, submitted) and the results reveal that the compounds within the ConMedNP library show some degree of conformational
Summary
Natural products (NPs) have always played an important role in drug discovery until today (Li and Vederas 2009; Chin et al 2006; Newman 2008; Harvey 2008; Koehn and Carter 2005) This is because they both serve as active principles in drugs and as templates for the synthesis of new drugs (Newman 2008; Efange 2002). The fact that more and more drugs fail to enter the market as a result of poor pharmacokinetic profiles, has necessitated the inclusion of pharmacokinetic considerations at earlier stages of drug discovery programs (Hodgson 2001; Navia and Chaturvedi 1996) This requires the search for lead compounds which can be orally absorbed, transported to their desired site of action, not metabolised into toxic products before reaching the targeted site of action and eliminated from the body before accumulating in sufficient amounts that may produce adverse side effects. The sum of the above mentioned properties is often referred to as ADME (absorption, distribution, metabolism and elimination) properties, or better still ADMET, ADME/T or ADMETox (when toxicity assessment is included)
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