2 research outputs found
Evaluation of Plasmodium falciparum K13 gene polymorphism and susceptibility to dihydroartemisinin in an endemic area
Asia, and its reduced sensitivity has been reported in other regions. This study aims to determine
parasite susceptibility to the bioactive form of artemisinin derivatives- dihydroartemisinin (DHA)-,
and to detect the K13 polymorphism in isolates from an endemic area of Nigeria. Methods: Ex-vivo
response in 55 parasites isolates obtained from malaria-positive patients were exposed to pulseDHA
concentration and cultured for 66 hours ex-vivo. Parasite ring stage survival (RSAex-vivo) relative to
unexposed matched control was determined by microscopy, and parasite growth was compared
using Mann-Whitney U-test at a significance level of P<0.05. The Kelch propeller gene was amplified
using specific primers, then sequenced and analyzed for single nucleotide polymorphisms (SNPs),
which were compared to reference PF3D7_1343700. Results: Overall, 151 of 375 (40.2%) individuals
were positive during the study period. In 55 selected isolates, there was increased growth in
unexposed wells but growth was inhibited in DHA-exposed wells, with growth rate between 14.9 –
96.7%. The mean RSAex-vivo value was 0.18 � 0.09%, 95% CI (0.15-0.20). There was no significant mutation
of the K13 gene in the parasite isolates evaluated. Conclusions: Plasmodium falciparum isolates
from this endemic area show high sensitivity to dihydroartemisinin ex-vivo, with no mutations
conferring artemisinin resistance. Continuous monitoring of parasite susceptibility to artemisinin
combination drugs should be intensified to reduce chances of artemisinin resistance in endemic
area
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