Lydia L. Lifongo

AfroDb: a select highly potent and diverse natural product library from African medicinal plants.

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.

The potential of anti-malarial compounds derived from African medicinal plants, part I: a pharmacological evaluation of alkaloids and terpenoids

Traditional medicine caters for about 80% of the health care needs of many rural populations around the world, especially in developing countries. In addition, plant-derived compounds have played key roles in drug discovery. Malaria is currently a public health concern in many countries in the world due to factors such as chemotherapy faced by resistance, poor hygienic conditions, poorly managed vector control programmes and no approved vaccines. In this review, an attempt has been made to assess the value of African medicinal plants for drug discovery by discussing the anti-malarial virtue of the derived phytochemicals that have been tested by in vitro and in vivo assays. This survey was focused on pure compounds derived from African flora which have exhibited anti-malarial properties with activities ranging from “very active” to “weakly active”. However, only the compounds which showed anti-malarial activities from “very active” to “moderately active” are discussed in this review. The activity of 278 compounds, mainly alkaloids, terpenoids, flavonoids, coumarines, phenolics, polyacetylenes, xanthones, quinones, steroids, and lignans have been discussed. The first part of this review series covers the activity of 171 compounds belonging to the alkaloid and terpenoid classes. Data available in the literature indicated that African flora hold an enormous potential for the development of phytomedicines for malaria.

CamMedNP: Building the Cameroonian 3D structural natural products database for virtual screening

BackgroundComputer-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 present CamMedNP - a new database beginning with more than 2,500 compounds of natural origin, along with some of their derivatives which were obtained through hemisynthesis. These are pure compounds which have been previously isolated and characterized using modern spectroscopic methods and published by several research teams spread across Cameroon.DescriptionIn the present study, 224 distinct medicinal plant species belonging to 55 plant families from the Cameroonian flora have been considered. About 80 % of these have been previously published and/or referenced in internationally recognized journals. For each compound, the optimized 3D structure, drug-like properties, plant source, collection site and currently known biological activities are given, as well as literature references. We have evaluated the “drug-likeness” of this database using Lipinski’s “Rule of Five”. A diversity analysis has been carried out in comparison with the ChemBridge diverse database.ConclusionCamMedNP could be highly useful for database screening and natural product lead generation programs.

Cameroonian medicinal plants: a bioactivity versus ethnobotanical survey and chemotaxonomic classification

BackgroundIn 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).MethodsOur 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.ResultsIn 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.ConclusionsIt 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.

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

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.

A Bioactivity Versus Ethnobotanical Survey of Medicinal Plants from Nigeria, West Africa

Traditional medicinal practices play a key role in health care systems in countries with developing economies. The aim of this survey was to validate the use of traditional medicine within local Nigerian communities. In this review, we examine the ethnobotanical uses of selected plant species from the Nigerian flora and attempt to correlate the activities of the isolated bioactive principles with known uses of the plant species in African traditional medicine. Thirty-three (33) plant species were identified and about 100 out of the 120 compounds identified with these plants matched with the ethnobotanical uses of the plants.

The uniqueness and therapeutic value of natural products from West African medicinal plants. Part I: uniqueness and chemotaxonomy

This review gives an in depth coverage of the natural products derived from West African medicinal plants with diverse biological activities. Unique compound classes from West African flora having remarkable biological activities have been highlighted, as well as a correlation between the biological activities of the derived compounds and the uses of the plants in traditional African medicine, and their chemotaxonomic classifications have been included in the discussion. In the first part of the review, the focus is on alkaloids and flavonoids.

The uniqueness and therapeutic value of natural products from West African medicinal plants, part II: terpenoids, geographical distribution and drug discovery

In this review series, an attempt has been made to give indepth coverage of natural products derived from West African medicinal plants with diverse biological activities. In part II of this series, emphasis has been laid on terpenoids from West African flora having remarkable biological activities, as well as a correlation between biological activities of the derived compounds and the uses of the plants in African traditional medicine. The impact of geographical distribution on the chemical contents of selected plant genera and their chemotaxonomic classifications have also been included in the discussion. Suggestions for drug discovery projects beginning with natural products from West Africa have also been provided.

The uniqueness and therapeutic value of natural products from West African medicinal plants, part III: least abundant compound classes

In this review, a continuation of our in-depth coverage of natural products derived from West African medicinal plants with diverse biological activities has been given. In the previous parts of this review series, the most abundant bioactive compound classes: terpenoids, flavonoids and alkaloids from West Africa were thoroughly investigated. We now focus on the least abundant compound classes (quinones, steroids, phenolics, glycosides, and other classes), having remarkable biological activities. A correlation between the biological activities of the derived compounds and the uses of the plants in African traditional medicine has been established.

The chemistry and bioactivity of Southern African flora I: a bioactivity versus ethnobotanical survey of alkaloid and terpenoid classes

As a whole, the African continent is highly endowed with a huge floral biodiversity. Natural products which have been isolated from plants growing in this region have shown interesting chemical structures with diverse biological activities, which could serve as a starting point for drug discovery. In this study, a literature survey led to the collection of 864 secondary metabolites from 101 plant species from 57 plant families. A correlation between the known biological activities of isolated compounds and the ethnobotanical uses of the plants has been attempted. This review is a survey of the bioactivities of alkaloids and terpenoids which have been isolated from Southern African flora versus the ethnobotanical uses of the plants used in Southern African traditional medicine.