Robyn van Zyl

University of the Witwatersrand | wits · Pharmacology Division Department of Pharmacy and Pharmacology

Naphthyl bearing 1,3,4-thiadiazoleacetamides targeting the parasitic folate pathway as antimalarials and antileishmanial agents.

Malaria is transmitted by infected female Anopheles mosquitoes, and An. arabiensis is a main malaria vector in arid African countries. Like other anophelines, its life cycle comprises of three aquatic stages; egg, larva, and pupa, followed by a free flying adult stage. Current vector control interventions using synthetic insecticides target these s...

Malaria vector control relies on the use of insecticides for indoor residual spraying and long-lasting bed nets. However, insecticide resistance to pyrethroids among others, has escalated. Anopheles funestus, one of the major African malaria vectors, has attained significant levels of resistance to pyrethroids. Overexpressed P450 monooxygenases hav...

Current studies on Anopheles anticholinesterase insecticides are focusing on identifying agents with high selectivity towards Anopheles over mammalian targets. Acetylcholinesterase (AChE) from electric eel is often used as the bioequivalent enzyme to study ligands designed for activity and inhibition in human. In this study, previously identified d...

Anopheles gambiae, An. coluzzii, An. arabiensis, and An. funestus are major vectors in high malaria endemic African regions. Various terpenoid classes form the main chemical constituent repository of essential oils, many of which have been shown to possess insecticidal effects against Anopheles species. The current study aimed to assess the bioacti...

The insect nervous system is critical for its functional integrity. The cholinergic system, of which acetylcholinesterase (AChE) is a key enzyme, is essential to the Anopheles (consisting of major malaria vector species) nervous system. Furthermore, the nervous system is also the primary target site for insecticides used in malaria vector control p...

Background: Antibiotics are miracles of science and critical for many surgical procedures. However, the emergence of multidrug resistant pathogens resulting from inappropriate antibiotic use is a threat to modern medicine. This study aimed to determine the appropriateness of antibiotic use, cost, consumption and impact of an antibiotic stewardship...

Organophosphates (OPs) used as potent insecticides for malaria vector control, covalently phosphorylate the catalytic serine residue of Anopheles gambiae AChE (AgAChE) in a reaction that liberates their leaving groups. In the recent 10-year insecticide use assessment, OPs were the most frequently used World Health Organization prequalified insectic...

Objective: The objective of this scoping review was to identify the available evidence on antimicrobial stewardship programs for teaching medical students about rational antimicrobial use, including the content taught and the method of instruction used. Introduction: Antibiotics are a precious resource whose discovery have saved millions of live...

Objectives: The objectives of this study were to assess the knowledge and perceptions of final year medical students about antibiotic resistance and antibiotic use to assist in the development of an antibiotic stewardship curriculum for teaching medical students in South Africa and Nigeria and the principles of prudent antibiotic prescribing. Met...

Presently, artemisinin-based combination therapy (ACT) is the first-line therapy of Plasmodium falciparum malaria. With the emergence of malaria parasites that are resistant to ACT, alternative antimalarial therapies are urgently needed. In line with this, we designed and synthesised a series of novel N-(7-chloroquinolin-4-yl)-N'-(4,6-diphenylpyrim...

Objective: The objective of this scoping review is to identify the available evidence on antimicrobial stewardship programs for teaching medical students about rational antimicrobial use, including the content taught and the method of instruction used. Introduction: Antibiotics are life-saving drugs and their discovery is one of the most importa...

A series of 3',4'‐dihydro‐1'H‐spiro(indoline‐3,2'‐quinolin)‐2‐ones were prepared by the inverse electron demand aza Diels‐Alder reaction (Povarov reaction) of imines derived from isatin and substituted anilines, and the electron rich alkenes trans‐isoeugenol and 3,4‐dihydro‐2H‐pyran. These compounds were assessed for in vitro antiplasmodial activit...

Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against...

About 40% of the world’s population lives in malaria zones where it presents a challenging health problem. Malaria treatment and prevention have been hindered by drug resistance. Bisphosphonates have been found to be active against Trypanosoma cruzi and Plasmodium falciparum that cause Chaga’s disease and malaria respectively. However, bisphosphona...

With the summer holidays fast approaching, holidaymakers will be planning their trip across Africa and the globe. Patients need to be aware of the risks of mosquito bites and contracting malaria. Malaria is endemic in the Limpopo, Mpumalanga and Northern KwaZulu-Natal provinces, with several cases of travel or Odyssean malaria being reported around...

Polyamidoamines were synthesized by Michael-type polyaddition reaction and conjugates characterized by ¹H NMR, ³¹ Mosmann, T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. J. Immunol. Meth. 1983, 65, 55–63.[Crossref], [PubMed], [Web of Science ®] [Google Scholar]P NMR, FTIR, SEM, an...

Literature reports several recent attempts to load a single drug onto one carrier to improve drug efficacy. An ideal anticancer drug would result from anchoring two anticancer drugs on a single carrier to exploit the advantage of possible synergistic interactions between the drugs, whilst targeting different sites in the cancer cell. This work pres...

Background: Pinene is a bicyclic monoterpene consisting of α- and β-constitutional isomers, with both structural isomers having enantiomers: (+)-α-, (-)-α-, (+)-β- and (-)-β-pinene. Isomers and enantiomers are well known to contribute contrasting pharmacological properties. These effects were investigated to identify new antimalarial and insecticid...

Polyamidoamine prodrugs containing ferrocene derivatives and neridronate were successfully synthesized and characterized by NMR, FTIR, SEM, and EDX analyses. Appearance of characteristic peaks in 1 H and 31 P NMR or EDX spectra were used to confirm the presence of neridronate or ferrocene in the conjugates and co-conjugates. In vitro evaluation of...

Polyaspartamides conjugates and co-conjugates containing platinum(II) complex and bisphosphonate were synthesized by stepwise reaction of polysuccinimide with selected primary amines. The first step was achieved by aminolytic ring opening of polysuccinimide and afforded conjugates containing bisphosphonate and dihydroxylato ligand for platinum chel...

In an endeavor to develop efficacious antiprotozoal agents 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives (5-14) were synthesized, characterized and biologically evaluated for antiprotozoal activity. The compounds were screened in vitro against the HM1: IMSS strain of Entamoeba histolytica and NF54 chloroquine-sensit...

The arrival of our summer rains brings with it Anopheles mosquitos buzzing around our ankles with the prospect of a nutritious meal. Unbeknownst to the female Anopheles mosquito, she has increased the risk of our becoming an annual statistic by being infected with malaria. Malaria is endemic in the Limpopo, Mpumalanga and Northern KwaZulu-Natal pro...

The design, synthesis and biological evaluation of a series of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines is described. These compounds exhibited in vitro antiplasmodial activity in the low nanomolar range against both drug sensitive and drug resistant strains of P. falciparum, with 1-(3-(2,4-dichlorophenoxy)propyl)-6-phenyl-1,6-dihydro-1,3,5-t...

Antimalarial activities of salts of aminoquinolines with hydroxyaromatic acids were found to be higher than the parent components. The IC50 values of the salts were in the range of 5.9-20.3 μM against the chloroquine-resistant strain. Antimalarial actions on the parasites were found to be independent of iron chelation, inhibition of haemozoin forma...

Background Healthcare workers are often reluctant to start combination antiretroviral therapy (ART) in patients receiving tuberculosis (TB) treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects. Object To quantify changes in adherence to tuberculosis treatment following ART initiation. De...

In an endeavour to develop efficacious antiprotozoal agents 2-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]acetamide derivatives were synthesized and screened in vitro against the HM1:IMSS strain of E. histolytica and 3D7 strain of P. falciparum. Among the twenty-seven synthesized compounds, eleven evinced propitious anti-amoebic activity with IC50 val...

Background: Healthcare workers are often reluctant to start combination antiretroviral therapy (ART) in patients receiving tuberculosis (TB) treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects. Object: To quantify changes in adherence to tuberculosis treatment following ART initiation. De...

The present study reports the preparation and preliminary biological activity results of co-conjugates of platinum ferrocene based drugs by using a novel synthetic route for the incorporation of ferrocene into the carrier. The Fe content obtained by ICP-AES was found in the range of 1.8-2.3 % by mass for the conjugates and 1.4-2.0 % by mass for the...

Medicinal plant use plays an important role in the healthcare of many South Africans. Furthermore, in orthodox medicine, conventional antimicrobial agents are amongst the most commonly prescribed groups of drugs. Therefore, due to the prevalence of use of these two forms of healthcare, there is a high probability for their concurrent use. Thus, the...

One of the most commonly consumed and commercially relevant herbal teas in South Africa is rooibos tea, prepared from the plant, Aspalathus linearis (Burm. F.) Dahlg. In orthodox medicine, antimicrobial agents are amongst the most commonly prescribed groups of drugs and thus there is a considerable possibility for the concurrent use of these drugs...

Two new flavonolacyl glucosides, 3-O-methylquercetin 7-O-[beta-D-6"-(E-p-coumaroyl) glucopyranoside] (1) and 3,4 '-di-O-methylquercetin 7-O-[ beta-D-6"-(E-p-coumaroyl) glucopyranoside] (2), four known flavonol glycosides (3-5, 7) and one known dihydroflavonolglucoside (6) were isolated from the aril part of Schotia brachypetala with high-speed coun...

Medicinal plant use plays an important role in the healthcare of many South Africans. Furthermore, in orthodox medicine, conventional antimicrobial agents are amongst the most commonly prescribed groups of drugs. Therefore, due to the prevalence of use of these two forms of healthcare, there is a high probability for their concurrent use. Thus, the...

The development of new drugs is a priority in pharmaceutics in order to ensure human well-being which is being threatened by new diseases, the development of resistance to the existing drugs, and the existence of diseases that are currently incurable. Plant extracts used by traditional healers have not been satisfactorily explored as a source of ne...

South Africa has a rich diversity of plant species which contain various classes of bioactive compounds [1]. Seeds of these plants have been little studied from a chemical viewpoint and a survey of their constituents is of high interest. The source plants of these seeds may grow in areas with extreme climatic conditions, thus increasing the chances...

Southern Africa has a diverse botanical flora with numerous plants being used traditionally as phytomedicines. Only a minuscule number of these plants have been scientifically validated for their therapeutic potential as antimalarials and even fewer have had the active chemical compound/s isolated from them. In an attempt to evaluate our plant flor...

A variety of 8β,13β-dihydroxypodocarpane derivatives (V) (8 examples) are synthesized starting from naturally occurring diterpene (+)-manod.

A new series of chloroquinoline based chalcones were synthesized and evaluated for in vitro antiamoebic and antimalarial activities. The results showed that out of fifteen compounds, four were found to be more active against the Entamoeba histolytica; while one compound was moderatively active compared to the standard drug metronidazole (IC50=1.46...

8β,13β-Dihydroxypodocarpane and eight C-13 substituted derivatives were prepared from the precursor 8bhydroxy-13-podocarpanone synthesised from the naturally occurring diterpene (+)-manool. The synthetic compounds exhibited a range of anti-plasmodial activities (IC50 1-29 μM) and only induced minimal haemolysis of erythrocytes at concentrations 50...

8β,13β-Dihydroxypodocarpane and eight C-13 substituted derivatives were prepared from the precursor 8 b hydroxy-13-podocarpanone synthesised from the naturally occurring diterpene (+)-manool. The synthetic compounds exhibited a range of anti-plasmodial activities (IC50 1–29 μM) and only induced minimal haemolysis of erythrocytes at concentrations 5...

For Abstract see ChemInform Abstract in Full Text.

The aim of the study was to determine in vitro activity of the bark of Ozoroa sphaerocarpa R. Fern & A. Fern (Anacardiaceae), Breonadia salicina (Vahl) Hepper & J.I.R. Wood (Rubiaceae) and Syzygium cordatum Hochst ex C Krauss (Myrtaceae) against a diarrhoea-causing pathogen, Escherichia coli; as well as the pharmacological interactions present in t...

The pharmacological properties of essential oils have been widely studied. However the interaction and contribution of the individual constituents assayed singularly and in combination remains relatively unexplored. To investigate these possible interactions, various essential oil constituents (EOC's) were combined and the interactions on their ant...

Complex interactions between numerous components of essential oils often contribute to the pharmacological effect and therapeutic outcome. To further elucidate these interactions, several essential oil constituents (EOCs) were combined in different ratios and their inhibitory effects on the growth of bacteria and yeast determined using the minimum...

Cussonia species are used in African traditional medicine mainly against pain, inflammation, gastro-intestinal problems, malaria and sexually transmitted diseases. To summarise ethnomedicinal uses of Cussonia and to find scientific evidence in support of selected main uses. Using the minimum inhibitory concentration (MIC) method, leaves of 13 Cusso...

Ten South African Commiphora (Burseraceae) species were investigated to validate their use in traditional healing rites. The leaf and stem extracts of each species were analysed for the anti-oxidant (ABTS and DPPH assays), antimicrobial (MIC and death kinetic assays), anti-inflammatory (5-LOX assay), anticancer (SRB assay) properties, as well as th...

Hermannia species are widely used in traditional medicine in southern Africa, however no extensive study has been conducted on this genus. The acetone extracts of 12 indigenous Hermannia species (flowers, stems and leaves combined) were evaluated for various pharmacological activities. All investigated species displayed promising antimicrobial acti...

The in vitro phytochemical and pharmacological investigation of the non-volatile extracts of five South African Vitex species (Verbenaceae); V. obovata ssp. obovata, V. obovata ssp. wilmsii, V. pooara, V. rehmannii and V. zeyheri were investigated in order to validate their traditional use to treat a wide range of ailments such as malaria, wounds,...

The solvent extracts of aromatic plants contain both volatile (e.g. essential oils) and non-volatile compounds. The biological activities (antibacterial, anti-oxidant, antiplasmodial and anticancer) of the solvent extracts of three South African Salvia species (Salvia africana-caerulea, S. africana-lutea and S. lanceolata) were evaluated in the pre...

A novel series of 4-substituted 1-{[4-(10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene}thiosemicarbazide, 4a-4n, was synthesized in 9-21% yield by the condensation of 4-(10,15,20-triphenylporphyrin-5-yl)benzaldehyde (3) with various substituted thiosemicarbazides in presence of catalytic amount of AcOH. These compounds were assayed for in vitro...

Aromatic plants contain both volatile and non-volatile fractions and the chemical composition of these two fractions may be influenced by seasonal changes. The essential oil and solvent extracts of S. africana-caerulea, S. africana-lutea and S. lanceolata, collected at the same locality throughout the 2005 growing season, were compared in terms of...

Extracts of seventeen Salvia species used in traditional medicine in South Africa were subjected to biological testing. The potential ability to inhibit the in vitro growth/proliferation of Plasmodium falciparum (FCR-3 strain) and the cytotoxic effects on three human cancer cells [breast adenocarcinoma (MCF-7), colon adenocarcinoma (HT-29) and glio...

Seven known abietane diterpenes were isolated from five Plectranthus species, namely P. hadiensis, P. lucidus, P. ecklonii, P. purpuratus subsp. purpuratus and P. purpuratus subsp. tongaensis. The seven compounds were tested for their antiplasmodial activity and for their ability to inhibit β-haematin formation. Overall, they showed good activity (...

Despite commercial interest and ethnobotanical data, the pharmacological activities of a number of indigenous Pelargonium species hitherto remain poorly explored. The acetone extracts of twenty-one Pelargonium species (section Pelargonium) were included in this study. Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, potent anti-oxidant activit...

The antimicrobial, anti-oxidant and cytotoxic activities of the extracts obtained from 17 indigenous Agathosma species (19 samples) were investigated in order to validate the historic and continued use of Agathosma species in traditional healing. The antimicrobial activity was evaluated using the minimum inhibitory concentration (MIC) method on fou...

Leaves and rhizome methanol extracts of Albertisia delagoensis tested positive against Plasmodium falciparum, with a very low cytotoxic activity in leaves against the Graham cell line.

The acquisition of resistance by malaria parasites towards existing antimalarials has necessitated the development of new chemotherapeutic agents. The effect of vitamin B(12) derivatives on the formation of beta-haematin (synthetic haemozoin) was determined under conditions similar to those in the parasitic food vacuole (using chloroquine, a known...

An investigation of leaf indumentum, the identification of the essential oil components and assessment of various biological activities of Salvia albicaulis and S. dolomitica essential oils were carried out. Non-glandular and both peltate and capitate glandular trichomes were identified using scanning electron microscopy. The essential oil of S. al...

Extracts of the aerial parts of Salvia chamelaeagnea and L. leonurus were evaluated for the in vitro antibacterial activity when tested in combination against two Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) using the microdilution method. The minimum...

Helichrysum cymosum, an aromatic plant used in traditional medicine to treat respiratory ailments and wound infections is widely distributed throughout Southern Africa. Using bioassay-guided fractionation, an active compound was isolated using column chromatography and identified as the known phloroglucinol derivative, helihumulone (1). The antimic...

The essential oils from fresh aerial parts of four Salvia species indigenous to southern Africa were obtained by hydrodistillation and analyzed by GC and GC/MS. Quantitative rather than qualitative differences in oil composition were observed. Forty-three compounds in each species accounting for 78% (S. africana-caerulea), 78% (S. africana-lutea),...

The essential oil composition, antimicrobial, anti-inflammatory and cytotoxic activities of 17 indigenous Agathosma species (18 samples) were investigated in order to validate their use in traditional healing. The results were related to the chemical composition of the essential oils as determined by GC and GC/MS. The antimicrobial activity was eva...

The essential oils from fresh aerial parts of four Salvia species indigenous to southern Africa were obtained by hydrodistillation and analyzed by GC and GC/MS. Quantitative rather than qualitative differences in oil composition were observed. Forty-three compounds in each species accounting for 78% (S. africana-caerulea), 78% (S. africana-lutea),...

The essential oil of Salvia muirii L. Bol., a species indigenous to southern Africa was obtained by hydrodistillation (0.5%, v/f.w.) from the aerial parts and analyzed by GC and GC/MS. Thirty-nine components representing 98% of the oil were identified. The oil was dominated by monoterpene hydrocarbons (53%) and oxygen-containing monoterpenes (36%),...

Twenty nature identical essential oil constituents from seven structural groups were tested for antimalarial, antimicrobial, antioxidant and toxicity properties. The compounds displayed antimalarial activity (IC50 values ranging from 0.9 to 1528.8 μM) with varying toxicity (IC50 values ranging from 5.5 to 1358.4 μM). The data indicates that (-)-pul...

Salvia species (sage) are well known in folk medicine throughout the world. In South Africa sage is used against fever and digestive disorders. Three closely related South African species (Salvia stenophylla, Salvia repens and Salvia runcinata) were investigated for their anti-oxidant (DPPH assay); anti-inflammatory (5-lipoxygenase and cyclo-oxygen...

The antimalarial activity of the raw petroleum ether and dichloromethane extracts of the stems of Parinari capensis (Chrysobalanceae) was determined. Phytochemical investigation of these extracts led to the isolation of three diterpene lactones that possess antimalarial activity with IC(50) values of 0.54, 0.67, and 1.57 microg/mL. Although their a...

The antiplasmodial activity and toxicity data of 34 Aloe species and their main constituents were determined. A number of the methanol extracts possessed antimalarial activity where 50% of the parasite growth was inhibited (IC50 value) by 32 to 77μg ml-1 of the extract. The chemical common to the most active species is the anthrone C-glucoside homo...

The antiplasmodial activity and toxicity data of 34 Aloe species and their main constituents were determined. A number of the methanol extracts possessed antimalarial activity where 50% of the parasite growth was inhibited (IC50 value) by 32 to 77μgml⁻¹ of the extract. The chemical common to the most active species is the anthrone C-glucoside homon...

The development of novel chemotherapeutic agents has become an urgent task due to the development and rapid spread of drug resistance in Plasmodium falciparum, the protozoan parasite responsible for cerebral malaria. Cyclin-dependent kinases (CDKs) are essential for the regulation of the eukaryotic cell cycle, and several enzymes of this family hav...