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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 lives. They are used extensively in surgical procedures, cancer chemotherapy, and in the treatment of infectious diseases. However, the development of antimicrobial resistance and the slow rate of discovery of new agents with novel mechanisms of actions represent a huge threat to modern medicine. Inclusion criteria This scoping review considered papers that described medical school curricula that focused on the teaching and learning of the prescription of antimicrobial medication. Studies that described this concept in the curricula of other health profession students, such as nursing, pharmacy, or dentistry students, were excluded. Only studies published in English from 1996 onwards were included. Methods Eight databases were searched for both published and unpublished literature and gray literature. The JBI three-step process was followed and conducted by two reviewers. The scoping review followed an a priori published protocol. Full texts of selected citations were assessed against the inclusion criteria by two independent reviewers. Data were independently extracted by two reviewers. Disagreements were resolved through discussion, and the need for a third reviewer was not required. Data extraction was undertaken using a modified charting table developed for the review objectives. The findings are presented using the narrative synthesis. Results Thirteen studies were included in the review, with most of the papers originating from the United States of America and Europe; with one from developing countries. Didactic lectures and web-based distance learning were the most common modes of instruction used in the included papers. Six of the included papers presented the outcomes of their interventions; where different methods of assessment were used to evaluate students, that included baseline and post-instruction assessment or a series of short exams. Some of the concepts included in the teaching material included the use of antimicrobial agents, the prevention of antimicrobial resistance, antimicrobial stewardship, and infection prevention control. The programs (ranging from 75 minutes to 100 hours) were implemented from second to fourth year of study. Conclusions A wide range of interventions were used to teach the principles of antimicrobial stewardship to medical students. There is a need to further evaluate these programs through follow-up of students after graduation to determine whether the skills learned are retained.

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 bioactivity of terpenoids including four sesquiterpene alcohols, farnesol, (-)-α-bisabolol, cis-nerolidol, and trans-nerolidol; a phenylpropanoid, methyleugenol, and a monoterpene, (R)-(+)-limonene, using the larvicidal screening assay against the four Anopheles species. The mechanism of action was investigated through in vitro acetylcholinesterase inhibition assay and in silico molecular modelling. All six terpenoids showed potent larvicidal activity against the four Anopheles species. Insights into the mechanism of action revealed that the six terpenoids are strong AChE inhibitors against An. funestus and An. arabiensis, while there was a moderate inhibitory activity against An. gambiae AChE, but very weak activity against An. coluzzii. Interestingly, in the in silico study, farnesol established a favourable hydrogen bonding interaction with a conserved amino acid residue, Cys

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 activity against drug-sensitive and drug-resistant forms of the P. falciparum parasite. Three compounds derived from 3,4-dihydro-2H-pyran and four compounds derived from trans-isoeugenol showed antiplasmodial activity in the low micromolar range against the drug-resistant FCR-3 strain (1.52-4.20 µM). Only compounds derived from trans-isoeugenol showed antiplasmodial activity against the drug-sensitive 3D7 strain (1.31-1.80 µM).

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 derivatives of a potent AChE, donepezil, that have exhibited low activity on electric eel AChE were assessed for potential AChE-based larvicidal effects on four African malaria vectors; An. funestus, An. arabiensis, An. gambiae and An. coluzzii. This led to the identification of four larvicidal agents with a lead molecule, 1-benzyl-N-(thiazol-2-yl) piperidine-4-carboxamide 2 showing selectivity for An. arabiensis as a larvicidal AChE agent. Differential activities of this molecule on An. arabiensis and electric eel AChE targets were studied through molecular modelling. Homology modelling was used to generate a three-dimensional structure of the An. arabiensis AChE for this binding assay. The conformation of this molecule and corresponding interactions with the AChE catalytic site was markedly different between the two targets. Assessment of the differences between the AChE binding sites from electric eel, human and Anopheles revealed that the electric eel and human AChE proteins were very similar. In contrast, Anopheles AChE had a smaller cysteine residue in place of bulky phenylalanine group at the entrance to the catalytic site, and a smaller aspartic acid residue at the base of the active site gorge, in place of the bulky tyrosine residues. Results from this study suggest that this difference affects the ligand orientation and corresponding interactions at the catalytic site. The lead molecule 2 also formed more favourable interactions with An. arabiensis AChE model than other Anopheles AChE targets, possibly explaining the observed selectivity among other assessed Anopheles species. This study suggests that 1-benzyl-N-(thiazol-2-yl) piperidine-4-carboxamide 2 may be a lead compound for designing novel insecticides against Anopheles vectors with reduced toxic potential on humans.

ObjectivesThe 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.MethodsA cross-sectional study was conducted to determine the knowledge and perceptions of final year medical students in one South African and three Nigerian universities about prudent antibiotic use, antibiotic resistance and antibiotic stewardship. A 26-item questionnaire was administered electronically to students in three medical schools and a paper-based copy in the fourth.Key findingsA difference in the gap in knowledge between the two countries was identified; however, respondents from both countries had a similar understanding of antibiotic use and antibiotic resistance. Most respondents in South Africa (94.8%) and Nigeria (91.4%) agreed that antibiotics are overused in their countries. There was a significant difference between the number of respondents in the two countries who thought that there are new antibiotics available to treat resistant pathogens; 45.4% of Nigerian respondents agreed with the statement as compared to 9.6% of the South African respondents. Of the 10 vignettes answered correctly, South African respondents scored an average of 62.4% in the knowledge segment compared to 31.9% scored by the Nigerian respondents (P = 0.001). All of the South African (100%) and 98.3% of the Nigerian respondents indicated their desire for more education on appropriate antibiotic use.ConclusionsAlthough students from both countries had the same perception of antibiotic resistance, there was, however, a difference in their level of knowledge, which could have been improved in both countries. This should be addressed at an undergraduate curriculum level; as well as with continued education to reinforce antibiotic knowledge.

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-diphenylpyrimidin-2-yl)alkanediamine hybrids (6a-7c) and evaluated their inhibitory activity against the NF54 chloroquine-susceptible strain as a promising class of antimalarial compounds. The antiplasmodial screening revealed that seven analogues showed promising to good activity with half-maximal inhibitory concentration (IC50) = 0.32 μM–4.30 μM. Compound 7a with 1,4-diamine butyl linker and 4-hydroxyl phenyl on fourth and sixth position of pyrimidine core showed the most prominent activity with an IC50 value of 0.32 ± 0.06 μM, with a favourable safety profile of 9.79 to human kidney epithelial (HEK293) cells. The remaining six analogues showed moderate activity with IC50 values ranging from 7.50 μM to 83.01 μM. We further investigated the binding affinities of the molecules to two essential cytosolic P. falciparum heat shock protein 70 homologues; PfHsp70-1 and PfHsp70-z. Compound 7a exhibited the highest binding affinity for both PfHsp70s with KD in a lower nanomolar range (4.4–11.4 nM). Furthermore, molecular docking revealed that compounds 6, 6k, 7b and 7a exhibited better fitness in PfHsp70-1 with compound 7a showing the highest and lowest binding scores of −9.8 kcal/mol. Therefore, we speculate that PfHsp70-1 is one of the targets of these inhibitors. The bioisoteric replacement of the groups at phenyl ring at the fourth and sixth position of the pyrimidine core had a constructive association with antiplasmodial activity. The promising antiplasmodial activity of the synthesised analogues illustrates how crucial molecular hybridisation is as a strategy in the development of quinoline-pyrimidine hybrids as prospective antiprotozoal agents.

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.Antibiotics are life-saving drugs and their discovery is one of the most important advances of the 20th century. They have transformed modern medicine by playing a critical role in the management of infectious diseases. However, the rapid development of resistance of pathogens to antibiotics is gradually affecting this initial success. Antimicrobial stewardship programs have been shown to reduce the burden of antimicrobial resistance in hospitals.This scoping review will consider papers conducted in medical school curricula to improve the prescribing of antimicrobial medication. Studies that include other health profession students, such as nursing, pharmacy, or dentistry students, will be excluded. Studies published in English from 1996 onwards will be included.Databases to be searched are PubMed, Wiley Online library, CINAHL Complete, Web of Knowledge, Scopus and Education Resources Information Center. Unpublished studies and gray literature will be included. Searching will follow a three-step process and will be conducted by two reviewers. Data will be extracted by two independent reviewers. Any disagreements that arise between the reviewers during the study selection process or data extraction will be resolved through discussion, or with a third reviewer. Results will be presented in tabular or diagrammatic form, together with a narrative summary.

Polyamidoamines were synthesized by Michael-type polyaddition reaction and conjugates characterized by 1H NMR, 31P NMR, FTIR, SEM, and EDX. The biological evaluation of the new materials revealed 1...

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 car...

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 insecticides. Molecular modelling programs are best suited to display molecular interactions between ligands and the target proteins. The docking modes that generate ligand poses closer to the binding site show high accuracy in predicting the ligand binding mode. The implicit solvation approach such as molecular mechanics-generalized born surface area (MM-GBSA) is a more reliable method to predict ligand onformations and binding affinities. Apart from covalent docking studies being scarce, current molecular docking programs do not adequately possess the covalent docking reaction algorithm to display the molecular mechanism of OPs at the AgAChE catalytic site. This results into OP docking studies commonly being conducted through noncovalent pannels. The aim of this study was to establish the optimim covalent docking system for OPs through manual customization of Schrodinger's Glide covalent docking reaction algorithm. To achieve this, a newly customized covalent reaction algorithm was assessed on a set of ligands covering aromatic, non-aromatic and hydrophobic OPs and compared to the noncovalent docking results in terms of reliability based on the reported X-ray diffraction molecular interactions and crystal poses. The study established that by virtue of omitting the well-known OP hydrolysis, noncovalent mode suggested molecular interactions that were further from the catalytic triad and could not otherwise occur when the molecule is hydrolyzed as in the customized covalent docking mode. Moreover, the MM-GBSA concurred with the optimized covalent docking in eliminating such inaccurate molecular interactions. Additionally, the covalent docking mode confined the interactions and ligand poses to the catalytic site indicating relatively high accuracy and reliability. This study reports the optimized covalent docking panel that effectively confirmed the molecular mechanisms of OPs, as well as indentifying the corresponding amino acid residues required to stabilize the aromatic, non-aromatic and hydrophobic OPs at the AgAChE catalytic site in line with the reported X-ray diffraction studies. As such, the proposed manual customization of the Schrodinger's Glide covalent docking platform can be used to reliably predict molecular interactions between OPs and AgAChE target.

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-sensitive strain of Plasmodium falciparum. Among the synthesized compounds six exhibited promising antiamoebic activity with IC50 values (0.14-1.26μM) lower than the standard drug metronidazole (IC50 1.80μM). All nine compounds exhibited antimalarial activity (IC50 range: 1.42-19.62μM), while maintaining a favorable safety profile to host red blood cells. All the compounds were less effective as an antimalarial and more toxic (IC50 range: 14.67-81.24μM) than quinine (IC50: 275.6±16.46μM) against the human kidney epithelial cells. None of the compounds exhibited any inhibitory effect on the viability of Anopheles arabiensis mosquito larvae.

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-triazine-2,4-diamine hydrochloride identified as the most potent compound from this series against the drug resistant FCR-3 strain (IC50 2.66 nM). The compounds were not toxic to mammalian cells at therapeutic concentrations and were shown to be inhibitors of parasitic DHFR in a biochemical enzyme assay

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 values ranging from 0.41 to 1.80 μM) lower than the standard drug metronidazole (IC50 1.80 μM). All the compounds inhibited the in vitro growth of P. falciparum (IC50 range: 0.30–33.52 μM). Compounds A22 and A25 were found to be the most active antimalarial derivatives, and compound A16 the most active in inhibiting β-haematin formation; however compound A25 displayed the more favourable safety profile. The crystal structure for the compounds A7, A8, A12 and A21 was also determined. The molecular docking of crystal resolved inhibitors with PfDHFR allowed identification of stabilizing interactions within enzyme active sites. These compounds affirm the potential for further derivatives to enhance antiprotozoal activity whilst retaining their safety profile.

Two new flavonolacyl glucosides, 3- O -methylquercetin 7- O -[ β -D-6″-( E - p -coumaroyl) glucopyranoside] (1) and 3,4′-di- O -methylquercetin 7- O -[ β -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 countercurrent chromatography (HSCCC) as the primary chromatographic technique. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods and acid hydrolysis. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant, antibacterial and antimalarial activities of selected isolates were evaluated. Strong to moderate antioxidant activity (lowest IC 50 of 15.2 μM), moderate to weak antibacterial activity (lowest MIC of 0.13 mg/mL) and moderate antimalarial activity (lowest IC 50 of 5.18 μg/mL) compared to the positive controls were observed.

A new series of 4-aminochloroquinoline based sulfonamides were synthesized and evaluated for antiamoebic and antimalarial activities. Out of the eleven compounds evaluated (F1-F11), two of them (F3 and F10) showed good activity against Entamoeba histolytica (IC50

8β,13β-Dihydroxypodocarpane and eight C-13 substituted derivatives were prepared from the precursor 8β-hydroxy-13-podocarpanone synthesised from the naturally occurring diterpene (+)-manool. The synthetic compounds exhibited a range of anti-plasmodial activities (IC501–29 μM) and only induced minimal haemolysis of erythrocytes at concentrations 50 and 100 μM. No changes in the morphology of erythrocytes were detected at sub-haemolytic concentrations.

Aim of the study 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 their combination. Materials and methods In consultation with traditional healers, the plants were collected from the wild, dried and extracted with dichloromethane:methanol (1:1). Thereafter, antimicrobial activity of the individual plants and their different combinations was tested using a common diarrhoea pathogen, Escherichia coli by employing the minimum inhibitory concentration assay. Results Ozoroa sphaerocarpa was the most potent inhibitor of antimicrobial growth (MIC value of 1.2 mg/ml), followed by Syzygium cordatum (MIC value of 1.44 mgl/ml) and lastly Breonadia salicina (MIC value of 10.89 mg/ml). The combination between Syzygium cordatum and Ozoroa sphaerocarpa gave the strongest synergistic interaction (MIC value of 0.33 mg/ml); whilst that between Syzygium cordatum and Breonadia salicina was mildly synergistic (MIC value of 1.00 mg/ml). The triple combination (1:1:1) was also very effective in inhibiting microbial growth (MIC value of 0.44 mg/ml). The combined effect of these plants on toxicity was predominantly synergistic except for the combination of Ozoroa sphaerocarpa and Syzygium cordatum which was predominantly antagonistic (ΣFIC value of 1.48 ± 0.25). The triple combination had a favourable toxicity profile with an IC50 value of 155.76 ± 11.86 μg/ml. Conclusion This study supports the rationale by traditional healers to use the bark of Syzygium cordatum, Breonadia salicina and Ozoroa sphaerocarpa in combination for the treatment of diarrhoea.

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 inhibitor of haemozoin formation for comparison). Adenosylcobalamin (Ado-cbl), methylcobalamin (CH(3)-cbl) and aquocobalamin (H(2)O-cbl) were approximately forty times more effective inhibitors of beta-haematin formation than chloroquine, cyanocobalamin (CN-cbl) was slightly more inhibitory than chloroquine, while dicyanocobinamide had no effect. It is proposed that the cobalamins exert their inhibitory effect on beta-haematin formation by pi-interactions of their corrin ring with the Fe(III)-protoporphyrin ring and by hydrogen-bonding using their 5,6-dimethylbenzimidazole/ribose/sugar side-chain. The antimalarial activity for the cobalamins (Ado-cbl>CH(3)-cbl>H(2)O-cbl>CN-cbl) was found to be less than that for chloroquine or quinine. Ado-cbl, CH(3)-cbl and CN-cbl do not accumulate in the parasite food vacuole by pH trapping, but H(2)O-cbl does. Unlike humans, the malaria parasite has only one enzyme that uses cobalamin as a cofactor, namely methionine synthase, which is important for growth and metabolism. Thus cobalamins in very small amounts are necessary for Plasmodium falciparum growth but in larger amounts they display antimalarial properties.

Twenty nature identical essential oil constituents from seven structural groups were tested for antimalarial, antimicrobial, antioxidant and toxicity properties. The compounds displayed antimalaria...

WOS: 000239708300002, 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 evaluated using the minimum inhibitory concentration (MIC) method on four pathogens: Staphylococcus aureus (ATCC 12600), Bacillus cereus (ATCC 11778), Klebsiella pneumoniae (NCTC 9633) and Candida albicans (ATCC 10231). The anti-inflammatory activity was evaluated using the 5-lipoxygenase assay while the cytotoxic activity was determined using the MTT (3-[4,5-dimethyl-2-thiazol-yl]-2,5-diphenyl-2H-tetrazolium bromide) cellular viability assay. The antimicrobial assay revealed that the most active oil against C. albicans was A. collina (MIC value of 3 mg/mL) whilst the most active oils against B. cereus were A. crenulata and A. pungens (MIC values of 3 mg/mL). Nine of the species had MIC values of 4 mg/mL against the Grain-positive pathogen S. aureus. The oils showed less activity against the Gram-negative pathogen K pneumoniae. All the oils exhibited good in vitro anti-inflammatory activity with A. collina being the most potent (IC50 value of 25.98 +/- 1.83 mu g/mL). The results show that the oils were strong inhibitors of the enzyme 5-lipoxygenase. The oils proved to be toxic in the MTT assay displaying IC50 Values of < 0.0001 mu g/mL, which were relatively toxic when compared to a plant-derived compound such as quinine (IC50 value of 0.08 +/- 0.03 mu g/mL). The results revealed some relationships between the major components, some bioactivities and toxicities. The oils were found to differ qualitatively and quantitatively in compositions and their analysis resulted in the identification of a total of 322 compounds in 18 of the samples.

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 ...

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), 96% (S. chamelaeagnea) and 81% (S. lanceolata) of the total composition were identified. Salvia africana-caerulea and S. lanceolata were dominated by oxygen-containing sesquiterpenes (59% and 48%, respectively). Oxygen-containing monoterpenes dominated in S. chanuslaeagnea (43%), while monoterpene hydrocarbons (36%) were abundant in S. africana-lutea. Scanning electron and light microscopy of the indumentum of the leaves revealed the presence of glandular and non-glandular trichomes. Non-glandular point-shaped trichomes composed of two or three cells are common in all four species and two types of glandular trichomes were noted: peltate trichomes, with up to 16 head cells and a capitate type varying in the number of cells comprising the head and stalk. The oils were evaluated against two Gram-positive and two Gram-negative bacterial strains using the microdilution method and the MIC values ranged from 0.8 to 32 mg/mL. The oils exhibited antiplasmodial (5 < IC 50 < 9 pg/mL) and anti-inflammatory (43 < ICc 0 < 77 pg/mL) activity as determined by the [ 3 H]-hypoxanthine radiometric and 5-lipoxygenase methods, respectively. Compared to other naturally derived antiplasmodial compounds (e.g. quinine) the oils are more toxic to human kidney epithelium cells (MTT method) with the ICc 0 values ranging from 2-7 μg/mL. The oils exhibited poor antioxidant activity against the DPPH' radical at 100 pg/mL.

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. Design: A prospective observational cohort study of ART-naive individuals with baseline CD4 count between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by pill count,self-report, and electronic Medication Event Monitoring System (eMEMS) before and after initiation of ART. Results: ART tended to negatively affect adherence to TB treatment, with an 8% – 10% decrease in the proportion of patients adherent according to pill count and an 18% – 22% decrease in the proportion of patients adherent according to eMEMS in the first month following ART initiation, independent of the cut-off used to define adherence (90%, 95% or 100%). Reasons for non-adherence were multi factorial, and employment was the only predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence interval 1.06–16.0). Conclusion: Adherence support in the period immediately following ART initiation could optimise treatment outcomes for people living with TB and HIV.

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 have been identified in P. falciparum. In recent years, a number of purine-derived kinase inhibitors have been synthesised, some of which display selective activity against CDKs. This report describes a study in which various purine derivatives were screened for in vitro antimalarial activity. The erythrocytic asexual stages of the chloroquine-resistant P. falciparum strain (FCR-3) were cultivated in vitro in the presence of the various purines, and their effect on parasite proliferation was determined by the [3H]hypoxanthine incorporation assay. Our results show considerable variation in the sensitivity of P. falciparum to the different purines, as well as a general independence from their effect on purified starfish CDK1/cyclin B activity, which has been the standard assay used to identify CDK-specific inhibitors. Two subfamilies of purines with moderate to poor activity against CDK1/cyclin B activity showed submicromolar activity against P. falciparum. Structure-activity analysis indicates that certain structural features are associated with increased activity against P. falciparum. These features can be exploited to synthesise compounds with higher activity and specificity towards P. falciparum.

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.

A small set of novel 2,N6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines was prepared possessing a flexible tether between the exocyclic nitrogen bonded to C-6 of the 1,2-dihydro-1,3,5-triazine-4,6-diamine heterocycle and the distal aryl ring. Three zones were varied in this series of compounds, namely the nature of the substituent(s) on C-2; the nature of the substituent(s) on the distal aryl ring; as well as the nature and length of the flexible tether between the rings. The compound showing the best antimalarial activity (cycloguanil-resistant FCR-3 Plasmodium falciparum IC50 = 0.99 μM) was N6-(3-(4-chlorophenoxy)propyl)-2-(furan-2-yl)-1,2-dihydro-1,3,5-triazine-4,6-diamine hydrochloride.

Synthesis and in vitro evaluation for antiamoebic and antimalarial activities are reported.

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

A small set of novel 2,N6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines was prepared possessing a flexible tether between the exocyclic nitrogen bonded to C-6 of the 1,2-dihydro-1,3,5-triazine-4,6-diamine heterocycle and the distal aryl ring. Three zones were varied in this series of compounds, namely the nature of the substituent(s) on C-2; the nature of the substituent(s) on the distal aryl ring; as well as the nature and length of the flexible tether between the rings. The compound showing the best antimalarial activity (cycloguanil-resistant FCR-3 Plasmodium falciparum IC50 = 0.99 μM) was N6-(3-(4-chlorophenoxy)propyl)-2-(furan-2-yl)-1,2-dihydro-1,3,5-triazine-4,6-diamine hydrochloride.

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 (IC 50 = 1.46 μM). In contrast, in vitro antimalarial activity against the chloroquine-sensitive (3D7) strain of P. falciparum indicated relatively low activity when compared to controls such as chloroquine and quinine (IC 50 = 0.0065 μM and 0.14 μM, respectively). The toxicological studies of these compounds on human breast cancer MCF-7 cell line showed that all the compounds were non-toxic at the concentration range of 1.56–50 μM.

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 IC50 values of 0.54, 0.67, and 1.57 μg/mL. Although their antimalarial activity is promising, the toxicity profiles of these diterpene lactones prevent further biological evaluation. They could however be used effectively as lead compounds in the synthesis of novel antimalarial agents.

The emergence of drug resistant malaria has prompted an intensified search for new antimalarials or combinations of such drugs. Iron chelating agents may represent a new approach to antimalarial treatment and could possibly be used in combination with classical antimalarials. Plasmodium falciparum (FCR-3) strain used at a 1% haematocrit, was subjected to various combinations of the classic antimalarials (chloroquine, pyrimethamine and quinine) and iron chelating agents (desferrioxamine and 2,2'-bipyridyl) in vitro. Tritiated hypoxanthine incorporation was used to determine the growth of the malarial parasites. The iron chelating agents and classic antimalarials when tested alone were found to inhibit the growth of the late stages of the parasite. The combination of the classic antimalarials and iron chelating agents resulted in additive effects on the in-vitro growth of P. falciparum.

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 antiamoebic activity, and the results showed that out of 14 compounds 9 were found with IC(50) values lower than metronidazole corresponding to 1.05- to 4.7-fold increase in activity. MTT Assay showed that all the compounds are nontoxic to human kidney epithelial cell line. 4-(m-Toluidinyl)-1-{[4-(10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene}thiosemicarbazide (4h) showed the highest antiamoebic activity with least cytotoxicity. Some of the compounds were screened for their antimalarial activities and ability to inhibit beta-haematin formation, but none of them showed an activity better than chloroquine and quinine. Only one compound out of six showed an activity comparable to standard drug.

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 IC50 values of 0.54, 0.67, and 1.57 μg/mL. Although their antimalarial activity is promising, the toxicity profiles of these diterpene lactones prevent further biological evaluation. They could however be used effectively as lead compounds in the synthesis of novel antimalarial agents.

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 inhibitory concentration (MIC) microplate assay. When combined and tested against Candida Albicans, (+)-β-pinene interacted antagonistically with (-)-menthone (ΣFICT = 9.80), but synergistically with 1,8-cineole (ΣFICT = 0.35). Against Escherichia coli, the combination of E- and Z-(±)-nerolidol and geranyl acetate displayed an additive interaction (ΣFICT = 1.04); while a variable interaction was observed between E- and Z-(±)-nerolidol and eugenol with antagonism and synergy being observed at different ratios of each EOC. The combination of either carvacrol or eugenol with an antimicrobial agent (ciprofloxacin or amphotericin B) resulted in synergistic interactions against all microorganisms tested. These favourable results further support the use of essential oil constituents as adjuvants in the development of a new generation of phytopharmaceuticals that can be used in combination with synthetic drugs against drug-resistant microorganisms.

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 presence and absence of the essential oils. The solvent extract of S. africana-caerulea free of essential oil exhibited the best activity against Gram-positive bacteria (MIC value: 0.4 mg/mL), while the solvent extract containing essential oil of S. lanceolata was the most active against Gram-negative bacteria (MIC value: 2.0 mg/mL). No significant difference was obtained in the antiplasmodial activity of the solvent extract with or without the essential oils of S. africana-caerulea and S. lanceolata, while the activity of the solvent extract without essential oil was significantly higher than that of the solvent extract containing the essential oil in S. africana-lutea (p < 0.05). The toxicity profile of all three species was significantly higher (p < 0.05) with the solvent extracts containing essential oils than when assessed in the absence of the essential oil.