Fidele Ntie-Kang

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.

Control of malaria and other vector-borne protozoan diseases in the tropics: enduring challenges despite considerable progress and achievements

Vector-borne protozoan diseases represent a serious public health challenge, especially in the tropics where poverty together with vector-favorable climates are the aggravating factors. Each of the various strategies currently employed to face these scourges is seriously inadequate. Despite enormous efforts, vaccines—which represent the ideal weapon against these parasitic diseases—are yet to be sufficiently developed and implemented. Chemotherapy and vector control are therefore the sole effective attempts to minimize the disease burden. Nowadays, both strategies are also highly challenged by the phenomenon of drug and insecticide resistance, which affects virtually all interventions currently used. The recently growing support from international organizations and governments of some endemic countries is warmly welcome, and should be optimally exploited in the various approaches to drug and insecticide research and development to overcome the burden of these prevalent diseases, especially malaria, leishmaniasis, Human African Trypanosomiasis (HAT), and Chagas disease.

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.

ConMedNP: a natural product library from Central African medicinal plants for drug discovery

We assess the medicinal value and “drug-likeness” of ∼3200 compounds of natural origin, along with some of their derivatives which were obtained through hemisynthesis. In the present study, 376 distinct medicinal plant species belonging to 79 plant families from the Central African flora have been considered, based on data retrieved from literature sources. For each compound, the optimised 3D structure has been used to calculate physicochemical properties which determine oral availability on the basis of Lipinskis “Rule of Five”. A comparative analysis has been carried out with the “drug-like”, “lead-like”, and “fragment-like” subsets, containing respectively 1726, 738 and 155 compounds, as well as with our smaller previously published CamMedNP library and the Dictionary of Natural products. A diversity analysis has been carried out in comparison with the DIVERSet™ Database (containing 48 651 compounds) from ChemBridge. Our results prove that drug discovery, beginning with natural products from the Central African flora, could be promising. The 3D structures are available and could be useful for virtual screening and natural product lead generation programs.

Virtualizing the p-ANAPL Library: A Step towards Drug Discovery from African Medicinal Plants

Background Natural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted. Experimental approach A current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinski’s “Rule of Five” has been used to evaluate likely oral availability of the samples. Results A majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the “Rule of Five”. The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed. Conclusions and implications The p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns.

An in silico evaluation of the ADMET profile of the StreptomeDB database

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. This paper presents an assessment of the “drug-likeness” and pharmacokinetic profile of > 2,400 compounds of natural origin, currently available in the recently published StreptomeDB database.MethodsThe evaluation of “drug-likeness” was performed on the basis of Lipinski’s “Rule of Five”, while 46 computed physicochemical properties or molecular descriptors were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds.ResultsThis survey demonstrated that, of the computed molecular descriptors, about 28% of the compounds within the StreptomeDB database were compliant, having properties which fell within the range of ADMET properties of 95% of currently known drugs, while about 44% of the compounds had ≤ 2 violations. Moreover, about 50% of the compounds within the corresponding “drug-like” subset showed compliance, while >83% of the “drug-like” compounds had ≤ 2 violations.ConclusionsIn addition to the previously verified range of measured biological activities, the compounds in the StreptomeDB database show interesting DMPK profiles and hence could represent an important starting point for hit/lead discovery from natural sources. The generated data are available and could be highly useful for natural product lead generation programs.

Anti-trypanosomal activity of nigerian plants and their constituents.

African trypanosomiasis is a vector-borne parasitic disease causing serious risks to the lives of about 60 million people and 48 million cattle globally. Nigerian medicinal plants are known to contain a large variety of chemical structures and some of the plant extracts have been screened for antitrypanosomal activity, in the search for potential new drugs against the illness. We surveyed the literatures on plants and plant-derived products with antitrypanosomal activity from Nigerian flora published from 1990 to 2014. About 90 plants were identified, with 54 compounds as potential active agents and presented by plant families in alphabetical order. This review indicates that the Nigerian flora may be suitable as a starting point in searching for new and more efficient trypanocidal molecules.