Conrad V. Simoben

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.

Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part II: Alkaloids, Terpenoids and Flavonoids

Cancer stands as second most common cause of disease-related deaths in humans. Resistance of cancer to chemotherapy remains challenging to both scientists and physicians. Medicinal plants are known to contribute significantly to a large population of Africa, which is to a very large extent linked to folkloric claims which is part of their livelihood. In this review paper, the potential of naturally occurring anti-cancer agents from African flora has been explored, with suggested modes of action, where such data is available. Literature search revealed plant-derived compounds from African flora showing anti-cancer and/or cytotoxic activities, which have been tested in vitro and in vivo. This corresponds to 400 compounds (from mildly active to very active) covering various compound classes. However, in this part II, we only discussed the three major compound classes which are: flavonoids, alkaloids and terpenoids.

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.

Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants

Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Güner–Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa’s expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space.

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.

Compounds from African Medicinal Plants with Activities Against Selected Parasitic Diseases: Schistosomiasis, Trypanosomiasis and Leishmaniasis

Parasitic diseases continue to represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug discovery and possible further development of drugs for the treatment of parasitic diseases. In the discussion, emphasis has been laid on alkaloids, terpenoids, quinones, flavonoids and narrower compound classes of compounds with micromolar range activities against Schistosoma, Trypanosoma and Leishmania species. In each subparagraph, emphasis is laid on the compound subclasses with most promising in vitro and/or in vivo activities of plant extracts and isolated compounds. Suggestions for future drug development from African medicinal plants have also been provided. This review covering 167 references, including 82 compounds, provides information published within two decades (1997–2017).Graphical Abstract

Design of selective histone deacetylase inhibitors: rethinking classical pharmacophore

For two decades, a classical pharmacophore model comprising a zinc binding group, a linker and a cap group, has been used for the development of histone deacetylase (HDAC) inhibitors. However, some of the recently reported selective HDAC inhibitors targeting additional, usually subtype specific, cavities in the binding pocket show supplementary features which do not fit this classical pharmacophore. We, therefore, propose an extended pharmacophore model, which can describe almost all currently known HDAC inhibitors. This pharmacophore consists of six pharmacophoric features and should be helpful for the classification and design of selective HDAC inhibitors.

A Novel Class of Schistosoma mansoni Histone Deacetylase 8 (HDAC8) Inhibitors Identified by Structure-Based Virtual Screening and In Vitro Testing

A promising means in the search of new small molecules for the treatment of schistosomiasis (amongst other parasitic ailments) is by targeting the parasitic epigenome. In the present study, a docking based virtual screening procedure using the crystal structure of histone deacetylase 8 from Schistosoma mansoni (smHDAC8) was designed. From the developed screening protocol, we were able to identify eight novel N-(2,5-dioxopyrrolidin-3-yl)-n-alkylhydroxamate derivatives as smHDAC8 inhibitors with IC50 values ranging from 4.4–20.3 µM against smHDAC8. These newly identified inhibitors were further tested against human histone deacetylases (hsHDAC1, 6 and 8), and were found also to be exerting interesting activity against them. In silico prediction of the docking pose of the compounds was confirmed by the resolved crystal structure of one of the identified hits. This confirmed these compounds were able to chelate the catalytic zinc ion in a bidentate fashion, whilst showing an inverted binding mode of the hydroxamate group when compared to the reported smHDAC8/hydroxamates crystal structures. Therefore, they can be considered as new potential scaffold for the development of new smHDAC8 inhibitors by further investigation of their structure–activity relationship.

Computational Studies and Biosynthesis of Natural Products with Promising Anticancer Properties

We present an overview of computational approaches for the prediction of metabolic pathways by which plants biosynthesise compounds, with a focus on selected very prom‐ ising anticancer secondary metabolites from floral sources. We also provide an overview of databases for the retrieval of useful genomic data, discussing the strengths and limita‐ tions of selected prediction software and the main computational tools (and methods), which could be employed for the investigation of the uncharted routes towards the bio‐ synthesis of some of the identified anticancer metabolites from plant sources, eventually using specific examples to address some knowledge gaps when using these approaches.