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

• Main Authors: Ajani, Olayinka, Olasehinde, Grace, Dokunmu, Titilope, Diji-Geske, Ruth, Onileere, Olabode, Openibo, John, Oluseye, Oreoluwa, Chileke, Tochukwu, Adebiyi, Ezekiel
• Format: Conference Proceeding
• Language: English
• Subjects: Bark; Benzaldehyde; Biocompatibility; Body weight; Chemical compounds; Cold water; Coumarin; Drug dosages; Fourier transforms; Hydrazines; In vivo methods and tests; Maceration; Malaria; Metabolites; Mice; NMR; Nuclear magnetic resonance; Organic chemistry; Pharmacology; Reaction time; Synthesis; Toxicity testing; Toxicology
• ISSN: 0094-243X; 1551-7616
• DOI: 10.1063/1.5033396

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 oxygen-containing 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 < 0.05), dose dependent activity (> 80% inhibition of pa