Browsing by Author "Chirawurah, J.D."
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Item Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates(International Journal for Parasitology: Drugs and Drug Resistance, 2017-12) Chirawurah, J.D.; Ansah, F.; Nyarko, P.B.; Duodu, S.; Aniweh, Y.; Awandare, G.A.Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box. The potency and the efficacy of the Malaria Box Compounds have been determined mainly using laboratory strains of P. falciparum. This study investigated the potency of twenty compounds from the Malaria Box against four clinical isolates from Ghana, using optimized in vitro growth inhibitory assays. Seven out of the 20 compounds screened had 50% inhibitory concentration (IC50) below 500 nM. The most active among the selected compounds was MMV006087 (average IC50 of 30.79 nM). Variations in the potency of the Malaria Box Compounds were observed between P. falciparum clinical isolates and Dd2 strain. We also investigated the sensitivity of the clinical isolates to chloroquine and artesunate. The N093 clinical isolate was found to be resistant to chloroquine but showed high sensitivity to artesunate. The results underscore the importance of including clinical isolates with different drug-resistant backgrounds, in addition to laboratory strains, in validating potential compounds during antimalarial compound screening programs. © 2017 The AuthorsItem Antiplasmodial, Antitrypanosomal, and Cytotoxic Effects of Anthonotha macrophylla, Annickia polycarpa, Tieghemella heckelii, and Antrocaryon micraster Extracts(Advances in Pharmacological and Pharmaceutical Sciences, 2022) Dofuor, A.K.; Kumatia, E.K.; Chirawurah, J.D.; Ayertey, F.Malaria and trypanosomiasis are protozoan diseases which pose a devastating challenge to human health and productivity especially, in Africa where their respective vectors (female Anopheles mosquito and tsetse fly) abound. Various medicinal plants are used to treat these parasitic diseases. However, the scientific basis of their use and toxicological profiles have not been assessed. We have, therefore, evaluated the antiplasmodial, antitrypanosomal, and cytotoxic activities of four African medicinal plant extracts namely, Anthonotha macrophylla leaf (AML), Annickia polycarpa leaf (APLE), Tieghemella heckelii stem bark (THBE), and Antrocaryon micraster stem bark (AMSBE) extracts in vitro against P. falciparum (W2mef laboratory strain), T. brucei (GUTat 3.1 strain), and mammalian RAW 264.7 macrophage cell line, respectively. The most active antiplasmodial extract was AML (IC50 = 5.0 ± 0.08 μg/mL with SI of 21.9). THBE also, produced the most e¡ective antitrypanosomal activity (IC50 = 11.0 ± 0.09 μg/ mL and SI of 10.2) among the extracts. In addition, none of the extracts produced toxic e¡ect in the RAW 264.7 macrophage cell line except APLE which was moderately cytotoxic and also produced the least SI in both antitrypanosomal and antiplasmodial assays. These results suggest that AML and THBE could o¡er safe and alternative therapy for malaria and trypanosomiasis. This is the first study to report the antitrypanosomal and in vitro antiplasmodial activities of these four plants/plant parts. The cyptotoxicity of the plant parts used is also being reported for the first time except for the T. heckelii stem bark.Item Design of a Blood-Warming Device for Resource-Limited Settings(EuroJournals Publishing, Inc., 2013) Adams, C.F.; Chirawurah, J.D.; Agbekoh, P.E.; Kaufmann, E.E.Blood warming is usually required to get the temperature of blood to 37oC from storage temperatures of 1–6 oC to prevent hypothermia during transfusions. Needs assessment at various hospitals revealed that blood warming is a major challenge in Ghana. Local methods of warming blood include leaving blood bags on walls in the open at ambient temperature to warm, putting bags in warm water or leaving blood bags under running tap water. These methods are inefficient, unsafe and time consuming. Efficient blood warmers are available but they are very expensive and unaffordable for the resource limited hospitals surveyed. A cost effective, safe and efficient blood warming and thawing device was designed to address the above-mentioned problems in resource-limited settings. Materials and components were selected based on specifications obtained from potential users, functional analysis, existing products and standards. The components of the device are encased in a housing insulated with polymer foam to reduce heat loss to the environment. It is anticipated that this intervention will be invaluable in situations where quick blood transfusions are required to save lives.Item Development of Cooperative Primer-Based Real-Time PCR Assays for the Detection of Plasmodium malariae and Plasmodium ovale(The Journal of Molecular Diagnostics, 2021) Ansah, F.; Suurbaar, J.; Darko, D.; Anabire, N.G.; Blankson, S.O.; Domson, B.K.S.; Soulama, A.; Kpasra, P.; Chirawurah, J.D.; Amenga-Etego, L.; Kanyong, P.; Awandare, G.A.; Aniweh, Y.Plasmodium malariae and Plasmodium ovale are increasingly gaining public health attention as the global transmission of falciparum malaria is decreasing. However, the absence of reliable Plasmodium species-specific detection tools has hampered accurate diagnosis of these minor Plasmodium species. In this study, SYBR Greenebased real-time PCR assays were developed for the detection of P. malariae and P. ovale using cooperative primers that significantly limit the formation and propagation of primersdimers. Both the P. malariae and P. ovale cooperative primer-based assays had at least 10-fold lower detection limit compared with the corresponding conventional primer-based assays. More important, the cooperative primer-based assays were evaluated in a cross-sectional study using 560 samples obtained from two health facilities in Ghana. The prevalence rates of P. malariae and P. ovale among the combined study population were 18.6% (104/560) and 5.5% (31/560), respectively. Among the Plasmodium-positive cases, P. malariae and P. ovale mono-infections were 3.6% (18/499) and 1.0% (5/ 499), respectively, with the remaining being co-infections with Plasmodium falciparum. The study demonstrates the public health importance of including detection tools with lower detection limits in routine diagnosis and surveillance of nonfalciparum species. This will be necessary for comprehensively assessing the effectiveness of malaria interventions and control measures aimed toward global malaria elimination. (Item Marmesin isolated from Celtis durandii Engl. root bioactive fraction inhibits β-hematin formation and contributes to antiplasmodial activity(Elsevier Ireland Ltd, 2023) Chirawurah, J.D.; Ezenyi, I.C.; Sahal, D.; et al.ABSTRACT Ethnopharmacological relevance: Malaria is a leading cause of death in many developing countries, especially in sub-Saharan Africa. Nigeria is endowed with an abundance of medicinal plants, many of which are used to treat malaria. Celtis durandii Engl. is one such plant used as a traditional antimalarial remedy in southeast Nigeria. However, its antiplasmodial potential is poorly explored. Aim of the study: The study aimed at identifying the antiplasmodial components of C. durandii root extract through antiplasmodial activity-guided fractionation. Materials and methods: Dichloromethane/methanol mixture extract (1:1 v/v) of C. durandii root was prepared and partitioned against water to obtain the organic phase, which was further separated by column chromatography into nine (C1 – C9) fractions. The antiplasmodial activity was evaluated by in vitro screening of the different fractions against drug-sensitive and drug-resistant Plasmodium falciparum strains. Further purification of the active column fractions resulted in a potent anti-Plasmodial compound that was subsequently investigated for its effect on β-hematin formation. Additionally, the isolated compound was characterized and identified as mar mesin using mass spectrometry and nuclear magnetic resonance spectroscopy. Results: Celtis durandii root extract exhibited promising antiplasmodial activity {IC50 (μg/ml) 5.92, 6.04, and 6.92} against PfW2mef, PfINDO, and Pf3D7 respectively. Pooled fractions with good antiplasmodial activity {IC50 (μg/ml) Pf3D7: 3.99; PfINDO: 2.24} and selectivity for the parasites (SI: 21) yielded a compound that was fourteen-fold potent in antiplasmodial activity against Pf3D7(IC50: 0.28 μg/ml). It also inhibited β-hematin formation with an IC50 = 150 μM. Further studies using spectral data, literature, and chemical databases identified the purified compound as marmesin. Conclusion: This work has demonstrated that Celtis durandii root extract has good antiplasmodial activity against drug-sensitive and drug-resistant P. falciparum. The inhibition of β-hematin formation by marmesin accounts in part for this activity.Item Marmesin isolated from Celtis durandii Engl. root bioactive fraction inhibits β-hematin formation and contributes to antiplasmodial activity(Journal of Ethnopharmacology, 2023) Ezenyi, I.C.; Chirawurah, J.D.; Erhunse, N.; Agrawal, P.; Sahal, D.; Ijoli, J.O.Ethnopharmacological relevance: Malaria is a leading cause of death in many developing countries, especially in sub-Saharan Africa. Nigeria is endowed with an abundance of medicinal plants, many of which are used to treat malaria. Celtis durandii Engl. is one such plant used as a traditional antimalarial remedy in southeast Nigeria. However, its antiplasmodial potential is poorly explored. Aim of the study: The study aimed at identifying the antiplasmodial components of C. durandii root extract through antiplasmodial activity-guided fractionation. Materials and methods: Dichloromethane/methanol mixture extract (1:1 v/v) of C. durandii root was prepared and partitioned against water to obtain the organic phase, which was further separated by column chromatography into nine (C1 – C9) fractions. The antiplasmodial activity was evaluated by in vitro screening of the different fractions against drug-sensitive and drug-resistant Plasmodium falciparum strains. Further purification of the active column fractions resulted in a potent anti-Plasmodial compound that was subsequently investigated for its effect on β-hematin formation. Additionally, the isolated compound was characterized and identified as marmesin using mass spectrometry and nuclear magnetic resonance spectroscopy. Results: Celtis durandii root extract exhibited promising antiplasmodial activity {IC50 (μg/ml) 5.92, 6.04, and 6.92} against PfW2mef, PfINDO, and Pf3D7 respectively. Pooled fractions with good antiplasmodial activity {IC50 (μg/ml) Pf3D7: 3.99; PfINDO: 2.24} and selectivity for the parasites (SI: 21) yielded a compound that was fourteen-fold potent in antiplasmodial activity against Pf3D7(IC50: 0.28 μg/ml). It also inhibited β-hematin formation with an IC50 = 150 μM. Further studies using spectral data, literature, and chemical databases identified the purified compound as marmesin. Conclusion: This work has demonstrated that Celtis durandii root extract has good antiplasmodial activity against drug-sensitive and drug-resistant P. falciparum. The inhibition of β-hematin formation by marmesin accounts in part for this activity.