salicylates and Malaria

In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria.

Topics: Amines; Aminoquinolines; Animals; Antimalarials; Benzimidazoles; Coordination Complexes; Ferrous Compounds; HEK293 Cells; Humans; Imidazoles; Iridium; Ligands; Malaria; Metallocenes; Molecular Structure; Organometallic Compounds; Osmium; Palladium; Platinum; Quinolines; Rhodium; Ruthenium; Salicylates; Silanes; Tamoxifen; Thiosemicarbazones

Metabolic acidosis is associated with most severe malaria deaths in African children, and most deaths occur before maximum antimalarial action is achieved. Thus, specific acidosis treatment may reduce mortality. However, the underlying mechanisms remain poorly understood and no specific interventions have been developed. A detailed characterisation of this acidosis is critical in treatment development. We used the traditional and Stewart's approach to characterise acidosis in consecutive paediatric admissions for malaria and other acute non-surgical conditions to Kilifi District Hospital in Kenya. The overall acidosis prevalence was 21%. Gastroenteritis had the highest prevalence (61%). Both the mean albumin-corrected anion gap and the strong ion gap were high (>13 mmol/l and >0 mmol/l, respectively) in malaria, gastroenteritis, lower respiratory tract infection and malnutrition. Presence of salicylate in plasma was not associated with acidosis but was associated with signs of severe illness (odds ratio 2.11, 95% CI 1.1-4.2). In malaria, mean (95% CI) strong ion gap was 15 (14-7) mmol/l, and lactate, creatinine and inorganic phosphorous explained only approximately 40% of the variability in base excess (adjusted R2 = 0.397). Acidosis may be more common than previously recognised amongst paediatric admissions in Africa and is characterised by the presence of currently unidentified strong anions. In malaria, lactate and ketones, but not salicylate, are associated with acidosis. However, unidentified anions may be more important.

Topics: 3-Hydroxybutyric Acid; Acidosis; Acute Disease; Biomarkers; Child, Preschool; Creatinine; Female; Gastroenteritis; Hospitalization; Humans; Infant; Kenya; Ketones; Lactates; Lung Diseases; Malaria; Male; Malnutrition; Regression Analysis; Salicylates

Topics: Animals; Antimalarials; Cephaloridine; Dapsone; Diet; Evaluation Studies as Topic; Injections, Subcutaneous; Kinetics; Leprosy; Malaria; Methods; Mice; Mycobacterium leprae; Oxadiazoles; Pyridines; Rifampin; Salicylates; Streptovaricin; Viomycin

Topics: Acidosis; Acute Kidney Injury; Alcoholism; Anuria; Child; Diabetes Mellitus; Dialysis; Humans; Hypertension; Hypertension, Malignant; Hyponatremia; Malaria; Peritoneal Dialysis; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Uremia

Topics: Anemia; Anemia, Hemolytic; Barbiturates; Catalase; Cholinesterases; Genetics, Medical; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Humans; Hydrogen Peroxide; Isoniazid; Malaria; Pharmacogenetics; Pharmacology; Porphyrias; Primaquine; Salicylates; Succinylcholine; Toxicology