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author:("mba, James A")
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.  Assessing the pharmacokinetic profile of the CamMedNP natural products database: an in silico approach 
Background
Drug metabolism and pharmacokinetic (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. Computer-based methods are slowly gaining ground in this area and are often used as initial tools to eliminate 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 the discovery of a drug.
Results
In the present study, we present an in silico assessment of the DMPK profile of our recently published natural products database of 1,859 unique compounds derived from 224 species of medicinal plants from the Cameroonian forest. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination (ADME) of the compounds. This survey demonstrated that about 50% of the compounds within the Cameroonian medicinal plant and natural products (CamMedNP) database are compliant, having properties which fall within the range of ADME properties of >95% of currently known drugs, while >73% of the compounds have ≤2 violations. Moreover, about 72% of the compounds within the corresponding ‘drug-like’ subset showed compliance.
Conclusions
In addition to the previously verified levels of ‘drug-likeness’ and the diversity and the wide range of measured biological activities, the compounds in the CamMedNP database show interesting DMPK profiles and, hence, could represent an important starting point for hit/lead discovery from medicinal plants in Africa.
doi:10.1186/2191-2858-3-10
PMCID: PMC3767462  PMID: 24229455
ADMET; Database collection; Descriptors; In silico; Medicinal plants; Natural products
3.  Bioassay-guided discovery of antibacterial agents: in vitro screening of Peperomia vulcanica, Peperomia fernandopoioana and Scleria striatinux 
Background
The global burden of bacterial infections is high and has been further aggravated by increasing resistance to antibiotics. In the search for novel antibacterials, three medicinal plants: Peperomia vulcanica, Peperomia fernandopoioana (Piperaceae) and Scleria striatinux (Cyperaceae), were investigated for antibacterial activity and toxicity.
Methods
Crude extracts of these plants were tested by the disc diffusion method against six bacterial test organisms followed by bio-assay guided fractionation, isolation and testing of pure compounds. The minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations were measured by the microdilution method. The acute toxicity of the active extracts and cytotoxicity of the active compound were performed in mice and mammalian cells, respectively.
Results
The diameter of the zones of inhibition (DZI) of the extracts ranged from 7–13 mm on Escherichia coli and Staphylococcus aureus of which the methylene chloride:methanol [1:1] extract of Scleria striatinux recorded the highest activity (DZI = 13 mm). Twenty-nine pure compounds were screened and one, Okundoperoxide, isolated from S. striatinux, recorded a DZI ranging from 10–19 mm on S. aureus. The MICs and MBCs indicated that the Peperomias had broad-spectrum bacteriostatic activity. Toxicity tests showed that Okundoperoxide may have a low risk of toxicity with an LC50 of 46.88 μg/mL.
Conclusions
The antibacterial activity of these plants supports their use in traditional medicine. The pure compound, Okundoperoxide, may yield new antibacterial lead compounds following medicinal chemistry exploration.
doi:10.1186/1476-0711-11-10
PMCID: PMC3403929  PMID: 22549052
Resistance; Medicinal plants; Antibacterial compound; Toxicity
4.  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 1-4 (4)