PRECLINICAL IN VITRO STUDY ON AMIDINE-HYDROXAMIC ACID BASED ANTIMALARIAL DRUG CANDIDATE.

The emergence of drug resistant strains of malaria parasite has led to increased efforts to discover and develop new antimalarial drugs that are structurally distinct from already existing ones.This study was conducted to evaluate the antiplasmodial activity of novel amidine-hydroxamic acid derivatives. Chloroquine-sensitive – Pyrimethamine resistant Plasmodium falciparum 3D7 strain was cultured in vitro in O+ human red blood cells in RPMI 1640 medium supplemented with 10% heat inactivated O human serum, 25mM HEPES buffer, 50μg/ml penicillin and 50μg/ml streptomycin under a condition of 90% N2, 5% O2 and 5% CO2. Serially diluted drugs were seeded into 96-well microtitre plates and incubated with aliquots of parasite from 3D7 culture medium containing asynchronized stage of parasite at a parasitemia of 0.2% and an haematocrit of 4% and the asynchronized wild type P. falciparum blood sample at a parasitemia of 1% and 4% haematocrit. The results obtained from the inhibitory concentrations (IC50) analyses performed for the novel antimalarial drug candidate compound revealed that the test compound with the code OA2 has IC50 values of 15,960nM against Plasmodium falciparum 3D7 and 0.3941nM against the wild type Plasmodium falciparum, while the standard drugs Artemisinin and Chloroquine were 68.86nM and 68.24nM and 164.5nM and 59.0nM for the wild type and typed strain Plasmodium falciparum. From the result obtained, It can be inferred that OA2 is moderately active against the viability of P. falciparum in human blood cultures and hence may be promising antimalarial drug candidates

Malaria Diagnosis: Current Approaches and Future Prospects

Scaled up efforts by a consortia of organisations in the diagnosis, treatment and prevention of malaria have led to a significant reduction in the overall malaria mortality and morbidity in the past few years. Malaria has, nonetheless, remained one of the world’s most burdensome diseases with the over 214 million cases and 438,000 deaths recorded in 2015 (2.68% of global DALYs). This burden is unevenly domiciled in sub-Saharan Africa where 89% of all cases and 91% of all deaths occurred. These figures however, only represent a fraction of the actual global burden of Malaria as surveillance fails to cover most cases in sub-Saharan Africa where the majority of malaria endemic regions lack facilities for diagnosis, case management and active surveillance. The emergence of drug resistant strains of the Plasmodium species prompted WHO to recommend a confirmatory diagnosis of each case of Malaria before treatment. The workability of this recommendation however, begs to be questioned as the majority of all malaria diagnosis is done via Clinical diagnosis; which lacks precision, is still the major form of diagnosis in many malaria endemic regions, and contributes to the over-diagnosis of malaria and subsequent under-diagnosis of other febrile illnesses. Of higher import is the risk of the emergence of drug resistant species due to the unregulated antimalarial use caused by inaccurate clinical diagnosis. Microscopy, which is the gold standard of malaria diagnosis, and the Rapid Diagnostic Tests (RDT) for malaria antigens have proven to be very useful in the diagnosis of malaria giving high levels of specificity and sensitivity. They however have the downside of having relatively high limits of detection, invasiveness, being labour intensive and expensive in the light of the low income countries where malaria is endemic. More sophisticated tools such as those that employ nucleic acid techniques (Polymerase Chain Reaction and Gene probes) are not field deployable and are mostly applied for research purposes. This necessitates the need for new diagnostic approaches that are suited to the conditions found in malaria endemic regions. A range of novel diagnostic tools with a do-ityourself approach, leveraging on previously untapped diagnostic material such as urine are currently being assessed. These novel tools promise great results if successful. This review presents an overview of current diagnostic methods, the prospects in malaria diagnostics and finally makes an effort to recommend what an ideal malaria diagnostic tool should be made up of, all the while focusing on sub-Saharan Afric

Phytochemical and Antimicrobial Properties ofnMangifera indica Leaf Extracts

There have been reports of increasing development of drug resistance among human pathogens as well as undesirable side effects of certain antimicrobial agents.It is therefore necessary to search for new agents that are better, cheaper and without side effects for treating infectious diseases especially in developing countries. In this study, phytochemical composition and antimicrobial activities of aqueous and ethanolic extracts of leaves of Mangifera indica were investigated. Standard methods were employed to screen for the phytochemicals. Agar well diffusion method was used to determine the antimicrobial effects of aqueous and ethanolic extracts of M. indica leaves against seven different clinical isolates namely:Stapylococcus aureus, Micrococcus virians, M. leteus, Escherichia coli, Klebsellia pneumoniae, Pseudomonas aeruginosa and a fungus, Candida albicans. Phytochemical screening showed the presence of active pharmacological components such as tannins, saponins, cardiac glycoside, flavonoid and alkaloids. Aqueous extract demonstrated a higher activity than the ethanolic extract. S. aureus showed highest sensitivity to the aqueous extracts with MIC 31.25mg/mL. Least sensitivity was observed in K. pneumoniae and Candida albicans with MIC 125mg/mL each in the two extracts.M. indica exhibited significant antimicrobial activity comparable to gentamicin which is used as control in this study

Structure-Based Design Synthesis of Functionalized 3-(5-(s- Phenyl)-4H-pyrazol-3-yl)-2H-chromen-2-one Motifs and Indigenous Plant Extracts and Their Antimalarial Potential

Resistance of the malaria parasite to conventional therapeutic agents calls for increased efforts in antimalarial drug discovery. Current efforts should be targeted at developing safe and affordable new agents to counter the spread of malaria parasites that are resistant to existing therapy. In this study, toxicological and in vivo antiplasmodial properties of 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-42H-chromen-2, Mangifera indica and Tithonia diversifolia in swiss albino mice models, Musmusculus were investigated. 2H-Chromen-2-one also known as coumarin is highly privileged oxygencontaining heterocyclic entity which are present in plant kingdom as secondary metabolites. The maceration technique of crude drug extraction was employed using cold water extraction. Toxicological analysis was carried out using Lorke’s method for acute toxicity testing while the chemosuppressive activity was carried out using Peter’s four day test on early infection. We also report the synthesis of functionalized 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-2H-chromen-2-one motifs via microwave assisted synthetic approach and isolation of indigenous plant extract in order to investigate their antimalarial efficacy. The condensation reaction of 3-acetylcoumarin with various benzaldehyde derivatives resulted in the formation of 3-[3-acryloyl]-2H-chromen-2-one which was subsequently reaction the hydrazine hydrate via microwave assisted hydrazinolysis to afford the targeted 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-2H-chromen-2-one motifs. The chemical structures were confirmed by analytical data and spectroscopic means such as FT-IR, UV, 1H NMR, 13C NMR and DEPT-135. The microwave assisted reaction was remarkably successful and gave targeted 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-2H-chromen- 2-one motifs in higher yields at lesser reaction time compared to conventional heating method. The LD50 of the aqueous extracts of the leaves and stem bark Mangifera indica was established to be ± 707.11 mg/kg b.w., p.o. (body weight, administered orally) in mice. Tithonia diversifolia aqueous leaf extracts is non-toxic at doses as high as 1000 mg/kg while the LD50 of the ethanolic leaf extracts was established to be ± 707.11 mg/kg b.w., p.o. in mice. The in vivo antiplasmodial activity was studied in chloroquine-sensitive Plasmodium berghei berghei - NK65 infected mice. All the plant extracts, at the doses (100, 200 and 400 mg/kg b.w., p.o.) used, produced significant (p 80% inhibition of parasitaemia at maximum dose) against the parasite in the suppressive tests. The in vitro antimalarial screening of the synthesized compounds is presently on-going and the finding will be reported in due course

Phytochemical and Antimicrobial Properties of Mangifera indica Leaf Extracts

There have been reports of increasing development of drug resistance among human pathogens as well as undesirable side effects of certain antimicrobial agents.It is therefore necessary to search for new agents that are better, cheaper and without side effects for treating infectious diseases especially in developing countries. In this study, phytochemical composition and antimicrobial activities of aqueous and ethanolic extracts of leaves of Mangifera indica were investigated. Standard methods were employed to screen for the phytochemicals. Agar well diffusion method was used to determine the antimicrobial effects of aqueous and ethanolic extracts of M. indica leaves against seven different clinical isolates namely:Stapylococcus aureus, Micrococcus virians, M. leteus, Escherichia coli, Klebsellia pneumoniae, Pseudomonas aeruginosa and a fungus, Candida albicans. Phytochemical screening showed the presence of active pharmacological components such as tannins, saponins, cardiac glycoside, flavonoid and alkaloids. Aqueous extract demonstrated a higher activity than the ethanolic extract. S. aureus showed highest sensitivity to the aqueous extracts with MIC 31.25mg/mL. Least sensitivity was observed in K. pneumoniae and Candida albicans with MIC 125mg/mL each in the two extracts.M. indica exhibited significant antimicrobial activity comparable to gentamicin which is used as control in this study