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1.  AfroDb: A Select Highly Potent and Diverse Natural Product Library from African Medicinal Plants 
PLoS ONE  2013;8(10):e78085.
Computer-aided drug design (CADD) often involves virtual screening (VS) of large compound datasets and the availability of such is vital for drug discovery protocols. We assess the bioactivity and “drug-likeness” of a relatively small but structurally diverse dataset (containing >1,000 compounds) from African medicinal plants, which have been tested and proven a wide range of biological activities. The geographical regions of collection of the medicinal plants cover the entire continent of Africa, based on data from literature sources and information from traditional healers. For each isolated compound, the three dimensional (3D) structure has been used to calculate physico-chemical properties used in the prediction of oral bioavailability on the basis of Lipinski’s “Rule of Five”. A comparative analysis has been carried out with the “drug-like”, “lead-like”, and “fragment-like” subsets, as well as with the Dictionary of Natural Products. A diversity analysis has been carried out in comparison with the ChemBridge diverse database. Furthermore, descriptors related to absorption, distribution, metabolism, excretion and toxicity (ADMET) have been used to predict the pharmacokinetic profile of the compounds within the dataset. Our results prove that drug discovery, beginning with natural products from the African flora, could be highly promising. The 3D structures are available and could be useful for virtual screening and natural product lead generation programs.
doi:10.1371/journal.pone.0078085
PMCID: PMC3813505  PMID: 24205103
2.  In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin 
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.
Electronic supplementary material
The online version of this article (doi:10.1186/2193-9616-1-12) contains supplementary material, which is available to authorized users.
doi:10.1186/2193-9616-1-12
PMCID: PMC4230438  PMID: 25505657
ADMET; Drug discovery; Descriptors; In silico; Medicinal plants; Natural products
3.  Cameroonian medicinal plants: a bioactivity versus ethnobotanical survey and chemotaxonomic classification 
Background
In Cameroon herbs are traditionally used to meet health care needs and plans are on the way to integrate traditional medicine in the health care system, even though the plans have not been put into action yet. The country however has a rich biodiversity, with ~8,620 plant species, some of which are commonly used in the treatment of several microbial infections and a range of diseases (malaria, trypanosomiasis, leishmaniasis, diabetes and tuberculosis).
Methods
Our survey consisted in collecting published data from the literature sources, mainly from PhD theses in Cameroonian university libraries and also using the author queries in major natural product and medicinal chemistry journals. The collected data includes plant sources, uses of plant material in traditional medicine, plant families, region of collection of plant material, isolated metabolites and type (e.g. flavonoid, terpenoid, etc.), measured biological activities of isolated compounds, and any comments on significance of isolated metabolites on the chemotaxonomic classification of the plant species. This data was compiled on a excel sheet and analysed.
Results
In this study, a literature survey led to the collection of data on 2,700 secondary metabolites, which have been previously isolated or derived from Cameroonian medicinal plants. This represents distinct phytochemicals derived from 312 plant species belonging to 67 plant families. The plant species are investigated in terms of chemical composition with respect to the various plant families. A correlation between the known biological activities of isolated compounds and the ethnobotanical uses of the plants is also attempted. Insight into future direction for natural product search within the Cameroonian forest and Savanna is provided.
Conclusions
It can be verified that a phytochemical search of active secondary metabolites, which is inspired by knowledge from the ethnobotanical uses of medicinal plants could be very vital in a drug discovery program from plant-derived bioactive compounds.
doi:10.1186/1472-6882-13-147
PMCID: PMC3703288  PMID: 23802859
Biological activities; Chemotaxonomy; Ethnobotany; Medicinal plants; Natural products
4.  Synthesis and in Vitro Biological Evaluation of Carbonyl Group-Containing Inhibitors of Vesicular Acetylcholine Transporter 
Journal of medicinal chemistry  2010;53(7):2825-2835.
To identify selective high-affinity inhibitors of the vesicular acetylcholine transporter (VAChT), we have interposed a carbonyl group between the phenyl and piperidyl groups of the prototypical VAChT ligand vesamicol, and its more potent analogues benzovesamicol and 5-aminobenzovesamicol. Of 33 compounds synthesized and tested, six display very high affinity for VAChT (Ki, 0.25 – 0.66 nM) and greater than 500-fold selectivity for VAChT over σ1 and σ2 receptors. Twelve compounds have high affinity (Ki, 1.0–10 nM) and good selectivity for VAChT. Furthermore, three halogenated compounds, namely, trans-3-[4-(4-fluorobenzoyl)piperidinyl]-2-hydroxy-1,2,3,4-tetrahydronaphthalene (28b) (Ki = 2.7 nM, VAChT/sigma selectivity index = 70), trans-3-[4-(5-iodothienylcarbonyl)piperidinyl]-2-hydroxy-1,2,3,4-tetrahydronaphthalene (28h) (Ki = 0.66 nM, VAChT/sigma selectivity index = 294), and 5-amino-3-[4-(p-fluorobenzoyl)piperidinyl]-2-hydroxy-1,2,3,4,-tetrahydronaphthalene (30b) (Ki = 2.40 nM, VAChT/sigma selectivity index = 410) display moderate to high selectivity for VAChT. These three compounds can be synthesized with the corresponding radioisotopes so as to serve as PET/SPECT probes for imaging the VAChT in vivo.
doi:10.1021/jm9017916
PMCID: PMC2853924  PMID: 20218624
PET imaging; vesicular acetylcholine transporter; cholinergic function; vesamicol
5.  Synthesis, In Vitro and In Vivo Evaluation of 18F-labeled PET Ligands for Imaging the Vesicular Acetylcholine Transporter 
Journal of medicinal chemistry  2009;52(5):1358-1369.
A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized and analogs were evaluated in vitro. (±)-trans-2-Hydroxy-3-(4-(4-[18F]fluorobenzoyl)piperidino)tetralin (9e) has Ki values of 2.70 nM for VAChT, 191 nM for σ1 and 251 nM for σ2. The racemic precursor (9d) was resolved via chiral HPLC and (±)-[18F]9e, (-)-[18F]9e, and (+)-[18F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [18F]/F- and Kryptofix/K2CO3 in DMSO with radiochemical yields ∼50-60% and specific activities >2000 mCi/μmol. (-)-[18F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum: cerebellum ratio of 1.88 by 30 min p.i.. MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[18F]9e in putamen versus cerebellum at 2 h. p.i. (-)-[18F]9e has potential to be a PET tracer for clinical imaging of the VAChT.
doi:10.1021/jm8012344
PMCID: PMC2765529  PMID: 19203271
PET imaging; vesicular acetylcholine transporter; cholinergic function; vesamicol
6.  Okundoperoxide, A Bicyclic Cyclofarnesylsesquiterpene Endoperoxide from Scleria striatinux with Antiplasmodial Activity 
Journal of natural products  2009;72(2):280-283.
Okundoperoxide (1) was isolated by bioassay-guided fractionation of extracts from Scleria striatinux (syn. S. striatonux) (Cyperaceae). The compound contains a cyclic endoperoxide structural moiety and possesses moderate antimalarial activity.
doi:10.1021/np800338p
PMCID: PMC2765531  PMID: 19199815

Results 1-6 (6)