A promising class of antiprotozoal agents, design and synthesis of novel Pyrimidine-Cinnamoyl hybrids.

Malaria, caused by parasitic protozoans of the Plasmodium genus, continues to be one of the greatest global health crises, especially in Africa. The emergence of antimalarial drug resistance continues to be a health problem necessitating an urgent need for alternative and cost-effective antimalarials. Using a molecular hybridization approach, we report the design and synthesis of an efficacious novel class of antiprotozoal agents; (E)-1-(4-(4,6-diphenylpyrimidin-2-yl)piperazin-1-yl)-3-phenyl prop-2-en-1-one derivatives (8a-r).

A content analysis of two african medical schools' antibiotic stewardship curricula.

Background: Antibiotics are precious substances that have saved millions of lives since their discovery, resulting in significant advances in modern medicine. However, antibiotic resistance and a slowdown in the discovery of new antibiotics with novel mechanisms of action are affecting the sustainability of antibiotics. The objective of this study was to describe the content of South African and Nigerian medical students' curricula with respect to prudent antimicrobial prescribing.

The insecticidal activity of essential oil constituents against pyrethroid-resistant Anopheles funestus (Diptera: Culicidae).

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.

In vitro and in silico analysis of the Anopheles anticholinesterase activity of terpenoids.

Anopheles gambiae, An. coluzzii, An. arabiensis, and An.

The in silico and in vitro analysis of donepezil derivatives for Anopheles acetylcholinesterase inhibition.

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.

Potential of Essential Oil-Based Anticholinesterase Insecticides against Vectors: A Review.

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 (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 programs.

Impact of an antibiotic stewardship programme in a surgical setting.

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 intervention round in a surgical ward setting.

Optimization of covalent docking for organophosphates interaction with Anopheles acetylcholinesterase.

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.

Educational antimicrobial stewardship programs in medical schools: a scoping review.

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.

Knowledge and perceptions about antibiotic resistance and prudent antibiotic prescribing among final year medical students in two African countries.

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.

Methods: A 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.

Design and synthesis of quinoline-pyrimidine inspired hybrids as potential plasmodial inhibitors.

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.

Educational antimicrobial stewardship programs in medical schools: a scoping review protocol.

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 important advances of the 20th century. They have transformed modern medicine by playing a critical role in the management of infectious diseases.

Preparation and antiplasmodial activity of 3',4'-dihydro-1'H-spiro(indoline-3,2'-quinolin)-2-ones.

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.

Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents.

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 a chloroquinone sensitive strain of (D10).

Design, synthesis and biological evaluation of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines as antiplasmodial antifolates.

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.

Impact of combination antiretroviral therapy initiation on adherence to antituberculosis treatment.

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-naïve individuals with baseline CD4 count between 50 cells/mm and 350 cells/mm at start of TB treatment at a primary care clinic in Johannesburg, South Africa.

Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents.

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 <5 μM). Three of the compounds (F5, F7 and F8) also displayed antimalarial activity against the chloroquine-resistant (FCR-3) strain of Plasmodium falciparum with IC50 values of 2 μM.

Expeditious synthesis and biological evaluation of novel 2,N6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines as potential antimalarials.

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.

Antiprotozoal activity of chloroquinoline based chalcones.

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 μM).

The anti-diarrhoeal properties of Breonadia salicina, Syzygium cordatum and Ozoroa sphaerocarpa when used in combination in Swazi traditional medicine.

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.

Synthesis and biological evaluation of novel 4-substituted 1-{[4-(10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene}thiosemicarbazides as new class of potential antiprotozoal agents.

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.

Antiplasmodial activity and cytotoxicity of Albertisia delagoensis.

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.

Naturally occurring cobalamins have antimalarial activity.

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.