Potential Antimalarials Research Articles

Evaluating the Antimalarial Potential of D-α-Tocopherol Polyethylene Glycol 1000 Succinate and α-Tocopherol, In Vivo Studies in Plasmodium berghei-Infected Mice and Molecular Docking Insights.

Oxidative stress is a pivotal factor in the pathogenesis of malaria, contributing to the development of conditions such as anemia, respiratory complications, and cerebral malaria. To counteract oxidative damage, we evaluated the effects of vitamin E (α-TOH) and D-α-tocopherol polyethylene glycol succinate 1000 (TPGS) supplementation on parasitemia progression, mortality rate, and blood-brain barrier (BBB) permeability in Plasmodium berghei ANKA-infected mice. The mice were divided into four groups: a control group (untreated and uninfected), an infected group (Pb), a TPGS+Pb group, and an α-TOH+Pb group. The results demonstrated that TPGS was more effective than α-TOH, exhibiting a lower parasitemia (9.59%) and mortality (40%) by day 12 and superior BBB protection in advanced infection stages. These findings suggest that TPGS may represent a promising therapeutic strategy for the management of malaria. Molecular docking analysis indicated that D-α-tocopherol polyethylene glycol succinate exhibited the highest binding affinity with plasmepsin 2 (-7.3 kcal/mol), while vitamin E demonstrated the strongest binding with plasmepsin 1 (-7.2 kcal/mol).

Identification of antimalarial phytoconstituents from Tinospora sinensis (Lour.) Merr. Stem by in vitro whole cell assay and multiple targets directed in silico screening against Plasmodium falciparum

Ethnopharmacological relevanceTinospora sinensis (Lour.) Merr., from the family Menispermaceae, is widely used in Indian folk and Ayurvedic medicine. Indigenous tribes such as the Tea-tribe and Chorei-tribe of Assam use its bark and stem as a herbal remedy to treat malaria and it is also traditionally employed for conditions such as dyspepsia, inflammation, fever, ulcers, jaundice, diabetes and various urinary, skin, and liver diseases. Aim of the studyThis study aims to identify and characterize antimalarial phytoconstituents from the active extract of T. sinensis stem by in vitro screening against both the Chloroquine-sensitive (Pf3D7) as well as Chloroquine-resistant (PfRKL-9) strains of Plasmodium falciparum, along with exploring potential targets and mechanisms using molecular docking and dynamics simulation studies. Materials and methodsT. sinensis stems were collected from Assam, India, and authenticated by the Botanical Survey of India. The plant materials were initially extracted with non-polar to polar solvents and screened for in vitro antimalarial potency against Pf3D7 and PfRKL-9. Then, the methanol extract was selected for bioassay-guided isolation of phytoconstituent(s). The isolated phytoconstituent(s) were screened for antimalarial potential and active compounds were further evaluated for cytotoxicity using the HEK-293 cell line. Structural characterization of the active compounds involved the use of UV–VIS, IR, NMR and HRMS analyses. Molecular docking and dynamics simulation studies were performed on selected targets from P. falciparum to predict binding affinities and mechanisms of action. ResultsFrom the methanol extract of T. sinensis stem, five phytoconstituents were isolated, including isoquinoline alkaloids Berberine (NG1) and Palmatine (NG2) showed the best antimalarial activity (IC50 < 1 μg/ml) against both Pf3D7 and PfRKL-9. Cytotoxicity assays confirmed their safety and selectivity. Molecular docking and dynamic simulation studies revealed that Berberine and Palmatine formed stable complexes with P. falciparum lysyl-tRNA synthetase and P. falciparum aminopeptidase N, respectively, indicating their potential as antimalarial leads. ConclusionThis study identifies two potent antimalarial phytoconstituents in the stem of T. sinensis, validating its traditional use and demonstrating its safety and efficacy for potential global application in malaria treatment.

Examination of the Toxicity Pattern and Influence of Azadirachta indica on Testicular Function and Expression of Proliferating Cell Nuclear Antigen in Plasmodium berghei-Infected Mice

Background: Malaria, a parasitic disease caused by a single-celled parasite called Plasmodium, poses a significant global health burden, especially in tropical regions such as Africa. The impact of malaria on human health is well-documented; however, its effects on the male reproductive system and the impact of herbal extracts remain underexplored. Objectives: This study aims to investigate Azadirachta indica's toxicity and its antimalarial potency's influence on testicular function and expression of proliferating cells nuclear antigen (PCNA). Methods: The antimalarial activity of Azadirachta indica was determined using standard procedures. Thirty male mice were used and grouped into six. Group 1 (normal control), group 2 (P. berghei infected only - negative control), group 3 (Plasmodium berghei infected + lonart - standard drug), group 4 (P. berghei infected + 100 mg/kg BWT crude ethanol extract), group 5 (P. berghei infected + 200 mg/kg BWT crude ethanol extract), group 6 (P. berghei infected + 400 mg/kg BWT crude ethanol extract). Administration of A. indica leaf extract to infected mice for four consecutive days demonstrated promising results. Results: The extract significantly suppressed parasite multiplication, ameliorated testicular damage, and improved sperm quality. The non-toxic extract also reduced oxidative stress in the testes, suggesting its potential effectiveness as phytotherapy against malaria-induced male reproductive impairments. Conclusions: The beneficial effects of A. indica emphasize its potential as a natural remedy for malaria-induced reproductive complications, offering a new avenue for therapeutic intervention in malaria-endemic regions. This study contributes to our knowledge of the intricate relationship between malaria and male reproductive health and provides valuable insights for future research and clinical applications.

The J Domain Proteins of Plasmodium knowlesi, a Zoonotic Malaria Parasite of Humans.

Plasmodium knowlesi is a zoonotic form of human malaria, the pathology of which is poorly understood. While the J domain protein (JDP) family has been extensively studied in Plasmodium falciparum, and shown to contribute to malaria pathology, there is currently very limited information on the P. knowlesi JDPs (PkJDPs). This review provides a critical analysis of the literature and publicly available data on PkJDPs. Interestingly, the P. knowlesi genome encodes at least 31 PkJDPs, with well over half belonging to the most diverse types which contain only the signature J domain (type IIIs, 19) or a corrupted version of the J domain (type IVs, 2) as evidence of their membership. The more typical PkJDPs containing other domains typical of JDPs in addition to the J domain are much fewer in number (type IIs, 8; type Is, 2). This study indentifies PkJDPs that are potentially involved in: folding of newly synthesized or misfolded proteins within the P. knowlesi cytosol (a canonical type I and certain typical type IIs); protein translocation (a type III) and folding (a type II) in the ER; and protein import into mitochondria (a type III). Interestingly, a type II PkJDP is potentially exported to the host cell cytosol where it may recruit human HSP70 for the trafficking and folding of other exported P. knowlesi proteins. Experimental studies are required on this fascinating family of proteins, not only to validate their role in the pathology of knowlesi malaria, but also because they represent potential anti-malarial drug targets.

CYP3A4-mediated metabolism of artemisinin to 10β-hydroxyartemisinin with comparable anti-malarial potency.

The most widely used anti-malarial drug artemisinin (ART) is metabolized extensively, but the therapeutic capacity of its major metabolite remains unknown. Whether the major metabolite of ART (ART-M) contributes to its antiplasmodial potency was investigated in this study. The metabolite identification and enzyme phenotyping of ART were performed using human liver microsomes (HLMs). The stereostructure of the major metabolite ART-M was elucidated by spectroscopic and X-ray crystallographic analysis. The anti-malarial activity of ART-M against two reference Plasmodium strains (Pf3D7 and PfDd2) was evaluated. The pharmacokinetic profiles of ART and its metabolite ART-M were investigated in healthy Chinese subjects after a recommended two-day oral dose of ART plus piperaquine. Pharmacodynamic parameters based on minimum inhibitory concentration (MIC50) and free plasma concentration were employed to evaluate the therapeutic potency of ART-M, including fAUC0-t/MIC50, fCmax/MIC50 and T > MIC50. A major metabolite 10β-hydroxyartemisinin (ART-M) was found for ART in human, and CYP3A4/3A5 was the major enzymes responsible for ART 10β-hydroxylation. Compared with ART (MIC50, 10.1nM against Pf3D7), weaker antiplasmodial activity was found for ART-M (MIC50, 61.4nM against Pf3D7). However, a 3.5-fold higher maximal free plasma concentration was achieved for ART-M (fCmax, 180.0nM vs. 51.8nM for ART). ART-M displayed comparable antiplasmodial potency to ART, in terms of fAUC0-t/MIC50 (12.5h), fCmax/MIC50 (2.8) and T > MIC50 (5h). The major metabolite 10β-hydroxyartemisinin contributes to the antiplasmodial efficacy of ART, which should be considered when evaluation of ART dosing regimens and/or clinical outcomes.

Genetic function algorithm (GFA) based QSAR, molecular design, and ADMET screening to assess the antimalarial potential of Amodiaquine derivatives

The ongoing fight against endemic diseases is complicated by the increasing resistance of malaria parasites to widely used drugs. As a result, the search for more effective antimalarial treatments continues. This research focuses on developing modified Amodiaquine analogues with enhanced efficacy. Additionally, the designed derivatives will be evaluated for their drug-likeness and pharmacokinetic properties. A predictive QSAR model was created using twenty-two Amodiaquine derivatives in the Material Studio to estimate the activity of newly designed derivatives. The most active derivative (used as a design template) was modified by applying descriptor implications at various positions, resulting in different derivatives. The drug-likeness and pharmacokinetic properties of these derivatives were assessed using SwissADME software and the pkCSM web application. Compound A-01, with the highest activity (pIC50 = 9.491), was selected as the prototype for designing thirteen improved derivatives. These derivatives were systematically created by altering substituents and saturations at specific positions on the template. All designed derivatives demonstrated greater activity than the template, Amodiaquine (pIC50 = 8.668), and Chloroquine (pIC50 = 8.111). Among them, the derivative ac, 4-((7-chloroquinolin-4-yl)amino)-2-(cyclohexyl(4-(pyridin-2-yl)piperazin-1-yl)methyl)phenol, proved to be the most potent. The designed derivatives functioned as substrates for P-glycoprotein, showed limited permeability across the blood-brain barrier, did not significantly penetrate the central nervous system, inhibited CYP1A2 and CYP2C19, and showed potential as renal OCT2 substrates. Thirteen Amodiaquine derivatives were developed with improved efficacy while adhering to Lipinski and Veber rules. These derivatives are largely non-toxic, skin-safe, and show promise for the development of effective antimalarial drugs.

Ultrasound-assisted synthesis and structure elucidation of novel quinoline-pyrazolo[1,5-a]pyrimidine hybrids for anti-malarial potential against drug-sensitive and drug-resistant malaria parasites and molecular docking

Ultrasound-assisted synthesis and structure elucidation of novel quinoline-pyrazolo[1,5-a]pyrimidine hybrids for anti-malarial potential against drug-sensitive and drug-resistant malaria parasites and molecular docking

Unraveling Cordia myxa’s anti-malarial potential: integrative insights from network pharmacology, molecular modeling, and machine learning

Malaria is a potentially fatal infective illness caused due to parasites that belong to the Plasmodium genus, which are transferred to humans with the help of the stings of affected female Anopheles mosquitoes, and it persists as a serious public wellness problem worldwide. Cordia myxa is a medicinal plant that possesses various medicinal characteristics like antimicrobial, anti-inflammation, antioxidant, and antidiabetic activities, which makes it an important natural resource for the therapy of different maladies in traditional medicine. In this investigation, a certain network pharmacology method has been utilized to identify the potent active components, possible targets as well as signaling pathways present in C. myxa in relation to malaria therapy. The active compounds were submitted to molecular docking approaches to validate their successful activity against the potential targets. The study concluded that three constituents named cosmosiin, stigmastanol, robinetin, and quercetin were highly active and could regulate the expression of Interleukin 6 (IL6) and Cysteine-aspartic acid protease 3 (CASP3), which may act as a potential therapeutic target for malaria treatment. These analyses are validated by molecular dynamics simulation which reflects on the overall structural stability of the intermolecular conformation and interactions. These results can also be witnessed in simulation-based trajectories binding free energies, which concluded the significant role of electrostatic and van der Waals energies in total intermolecular interactions. Finally, we utilized machine learning to predict the anti-malarial activity of C. myxa compounds, comparing them with approved drugs. Using the Chemprop model and MAIP predictions, we assessed ten compounds, revealing their potential as lead anti-malarial agents. This study establishes a groundwork for comprehending the function of the anti-malaria action of C. myxa.

Yeast-based assay to identify inhibitors of the malaria parasite sodium phosphate uptake transporter as potential novel antimalarial drugs

Malaria affects almost 250 million people annually and continues to be a significant threat to global public health. Infection with protozoan parasites from the genus Plasmodium causes malaria. The primary treatment for malaria is artemisinin-based combination therapies (ACTs). The spread of ACT-resistant parasites has undermined efforts to control and eradicate malaria. Thus, it is crucial to identify new targets for the development of novel antimalarial drugs. Phosphate is an essential nutrient for all cells. The Plasmodium falciparum genome encodes a single sodium-coupled inorganic phosphate transporter named PfPiT that is essential for parasite proliferation in the asexual blood stage. Thus, PfPiT inhibitors may be promising antimalarial drugs. Like Plasmodium, yeast requires phosphate to grow. We developed a Saccharomyces cerevisiae based growth assay to identify inhibitors of PfPiT. Genome editing was used to create a yeast strain where PfPiT was the only phosphate transporter. Using a radioactive [32P]phosphate uptake assay, the measured phosphate Km for PfPiT in yeast was 56 ± 7 μM in 1 mM NaCl at pH 7.4. The Km decreased to 24 ± 3 μM in 25 mM NaCl consistent with it being a Na+ coupled cotransporter. Conditions under which yeast growth was dependent on phosphate uptake mediated by PfPiT were identified and a 22-h growth assay was developed to screen for PfPiT inhibitors. In a screen of 21 compounds, two compounds were identified that inhibited the growth of the PfPiT strain but not that of the parental strain expressing Pho84, one of the five endogenous yeast phosphate transporters. Radioactive phosphate uptake experiments confirmed inhibition of phosphate uptake by the two compounds. The growth inhibition assay provides a simple and inexpensive approach to screen a large compound library for PfPiT inhibitors that may serve as starting points for the development of novel antimalarial drugs.

Antimalarial potentials of Solanum dasyphyllum fractions against Plasmodium berghei infected mice

BackgroundThe leaves of Solanum dasyphyllum are commonly utilized in the management of fever in traditional medicine, yet scientific evidence supporting their antimalarial effectiveness is lacking. ObjectiveThis study aimed to assess the antioxidant properties of solvent fractions derived from these leaves, alongside investigating antimalarial potential against Plasmodium berghei in mice. MethodsAntioxidant activity was evaluated through total phenolic content determination, DPPH radical scavenging, and Ferric ion reducing antioxidant power assay. The fractions were tested against Plasmodium berghei (NK65) in 4-day suppressive, prophylaxis, and curative models, with mice orally administered 1 % Tween 80 (control), Solanum dasyphyllum hexane fraction (SdHXF), Solanum dasyphyllum dichloromethane fraction (SdDMF), Solanum dasyphyllum ethyl-acetate fraction (SdEAF), and Solanum dasyphyllum aqueous fraction (SdAQF) (each at 125 mg/kg), and chloroquine (10 mg/kg). IC50 values were determined via linear regression analysis, and antimalarial study results were statistically analyzed using one-way ANOVA followed by Duncan multiple range tests, considering significance at P value < 0.05. ResultsThe SdHXF (60.4 %), SdDMF (56.8 %), SdEAF (86.4 %), and SdAQF (94.8 %) exhibited notable percentage chemosuppression compared to the control in the 4-day suppressive test. In the prophylaxis test, SdEAF (80.6 %) and SdAQF (80.0 %) demonstrated similar percentage chemosuppression. In the curative test, the mean survival time significantly increased in SdHXF (30.2 ± 1.3 days), SdDMF (30.8 ± 3.2 days), SdEAF (31.4 ± 2.3 days), and SdAQF (30.1 ± 2.0 days) compared to the control (10.3 ± 0.1 days). The antioxidant activity of the fractions increased with concentration; however, it was lower than that of the positive controls (gallic acid and ascorbic acid). ConclusionThese results suggest that the fractions possess potent antiplasmodial activity against Plasmodium berghei, particularly in the mid-polar fractions, indicating the potential of the plant as a source of novel antimalarial agents.

In vitro and in vivo evaluation of the antimalarial, anti-inflammatory and free radical scavenging potentials of the hydro-alcoholic leaf extract of Microdesmis puberula Hook. F. ex Planch (Pandaceae)

In vitro and in vivo evaluation of the antimalarial, anti-inflammatory and free radical scavenging potentials of the hydro-alcoholic leaf extract of Microdesmis puberula Hook. F. ex Planch (Pandaceae)

Dose-fractionation studies of a Plasmodium phosphatidylinositol 4-kinase inhibitor in a humanized mouse model of malaria.

UCT594 is a 2-aminopyrazine carboxylic acid Plasmodium phosphatidylinositol 4-kinase inhibitor with potent asexual blood-stage activity, the potential for interrupting transmission, as well as liver-stage activities. Herein, we investigated pharmacokinetic/pharmacodynamic (PK/PD) relationships relative to blood-stage activity toward predicting the human dose. Dose-fractionation studies were conducted in the Plasmodium falciparum NSG mouse model to determine the PK/PD indices of UCT594, using the in vivo minimum parasiticidal concentration as a threshold. UCT594 demonstrated concentration-dependent killing in the P. falciparum-infected NSG mouse model. Using this data and the preclinical pharmacokinetic data led to a low predicted human dose of <50 mg. This makes UCT594 an attractive potential antimalarial drug.

Ligand-based pharmacophore modeling, virtual screening, and molecular dynamics simulations of Pfhsp90 fingerprints in Plasmodium malaria treatment

The World Health Organization (WHO) documents malaria as one of the leading causes of high morbidity and mortality worldwide. The disease affects millions and kills thousands of people annually. Efforts to reduce the global burden of malaria have prompted the WHO to recommend prevention strategies such as using antimalarial drugs. However, these strategies have been ineffective because of antimalarial drug resistance. The only efficacious malaria treatment is Artemisinin-based Combination Therapy (ACT). However, the extended ACT clearance times, linked to the emergence of artemisinin monotherapy resistance recorded most recently in Africa and the Great Mekong region, pose a danger to its efficacy. Therefore, better efficacious antimalarial drugs are required. Since P. falciparum heat shock protein 90 (PfHsp90) is a well-characterized malaria drug target, this study uses it to discover more efficacious antimalarial drugs. An in silico approach was used to discover PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria using a molecular dynamics simulation (MDS) and hierarchical virtual screening. Geldanamycin (GDM), a well-known anti-PfHsp90 compound, was used to identify PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria by screening it against the ZINC20 database via the ZINCPHARMER web server. This virtual screening process resulted in 17 hits. These ZINCPHARMER hits were subjected to drug-likeness and pharmacokinetics properties analysis in the SwissADME web server, and nine of them satisfied the requirements. The nine ZINC20 compounds were docked with PfHsp90 using the PyRx software version 0.8 to understand their interactions. From the molecular docking results, ZINC09060002 (−8.2 kcal/mol), ZINC72133064 (−7.8 kcal/mol), ZINC72163401 (−7.7 kcal/mol), ZINC72358537 (−8.1 kcal/mol), and ZINC72358557 (−7.6 kcal/mol) had better binding affinities to PfHsp90 than GDM (−7.5 kcal/mol). The stability of these molecularly docked protein–inhibitor complexes was assessed through MDS using GROMACS 2022. ZINC72163401, ZINC72358537, and ZINC72358557 formed stable complexes with PfHsp90. The lead compounds were subjected to in vitro validation for their inhibitory capability. They showed promising inhibition of parasite growth with IC50 values ranging between 200 and 400 ng/mL. In this regard, the three PfHsp90 inhibitors can be further developed as potential antimalarial drugs. However, further structural optimization studies and clinical (in vivo) tests are necessary to ascertain the antimalarial activity of these compounds in humans.

Experimental and Computational Insights Into Organotellurium (IV) Complexes as Potent PfNDH2 Inhibitors: Synthesis, Characterization, and Antimalarial Evaluation

ABSTRACTThe study examines the binding affinities and pharmacological potential of synthesized metal compounds with PfNDH2 in Plasmodium falciparum. So as to identify the combatting agent for malaria, six new organotellurium (IV) complexes (8a–8f) were prepared through a condensation reaction of 3‐methyl‐2‐thiophene carboxaldehyde and p‐nitroaniline. The synthesized compounds were inclusively characterized through physical and spectral techniques signifying a distorted octahedral geometry. The reported complexes were screened for antimalarial and antioxidant activities and analyzed using micro assays and DPPH assays, respectively. Using docking interactions, the research evaluates the binding energies, hydrogen bonds, and steric interactions of various compounds with PfNDH2, aiming to identify promising candidates for antimalarial drug development. Among the compounds, 8f showed the strongest binding affinity, with the lowest binding energy of −135.626 kcal/mol, and diverse hydrogen bonds with the target enzyme. Structure‐based pharmacophore modeling revealed critical interaction profiles and selectivity scores for the compounds, with 8f emerging as a promising candidate. Molecular electrostatic potential (MESP) analysis offered insights into the distribution of electron density within the compounds, influencing their reactivity and potential as antimalarial agents. ADMET analysis highlighted the pharmacokinetic and toxicological profiles of the compounds, revealing critical aspects for optimizing safety and efficacy. Overall, the findings provide valuable information for further development and optimization of potential antimalarial drugs.

Antiplasmodial activities of n-hexane and water fractions of Dennettia tripetala leaf extract in Wistar rats

Many people die from malaria, a global health crisis. Most global malaria cases and deaths occur in sub-Saharan Africa. The rising resistance of Plasmodium spp. to antimalarial medications is hindering efforts to eradicate the illness. This study tested Dennettia tripetala leaf extract, N-hexane, and water fractions for antimalarial activity in rats. We used standard methods to screen Dennettia tripetala solvent (N-hexane and water) for phytochemical components. We tested the antimalarial potential of rats using Peters' 4-day suppressive, Rane's curative, and prophylactic tests. After conducting an exhaustive investigation, it was discovered that both fractions contained varying amounts of flavonoids, alkaloids, terpenoids, and saponins. There was a significant amount of antimalarial activity demonstrated by both fractions across all test models (P&lt;0.05). Compared to the water fraction, Dennettia tripetala's n-hexane fraction was highly chemosuppressive and curative. Dennettia tripetala n-hexane has chemoprophylactic, curative, and chemosuppressive effects. The curative effect was 62.3% to 72.4%, and the chemosuppressive effect was 51.2% to 88.5%. Chemoprophylactic activity was 32.1%–61.2%. At 250–1500 mg/kg, Combretum nigricans butanol suppressed 40.3%, 54.1%, and 69.1%, respectively. Therapeutic effects were 26.2%, 36.9%, and 34.5%, while chemoprophylaxis was 48.4%, 70.0%, and 87.4%. Both Dennettia tripetala solvent fractions have antimalarial activity, suggesting they may be effective in different malaria therapy stages.

Evaluation of antimalarial compounds in Prosopis africana stem bark fractions against Plasmodium berghei

Prosopis africana, a traditional medicinal plant for malaria treatment, requires further scientific evidence. This study aimed to assess the antimalarial potential of Prosopis africana stem bark fractions in Plasmodium berghei-infected mice and identify the responsible compounds. The aqueous extract underwent partitioning with n-hexane, ethyl acetate, and methanol, followed by antimalarial evaluation. F5 was the most potent fraction based on its antimalarial potential. The study pooled 36 chromatographic separation sub-fractions into five using TLC analysis Rf values. In Plasmodium berghei-infected mice, fraction F5 at 6.25, 12.5, 25, and 50 mg/kg body weight (bw) was tested for antimalarial activity. Compound analysis of F5 utilized ultra-performance liquid chromatography-quadrupolar mass spectrometry. Statistical analysis employed Analysis of Variance and Duncan's multiple range tests (p &lt; 0.05). The methanol, n-hexane, and ethylacetate extracts displayed suppression of P. berghei by 90%, 72.2%, and 73.6%, respectively. Methanol, n-hexane, and ethylacetate extracts suppressed P. berghei by 90%, 72.2%, and 73.6% respectively. F5 showed significantly higher chemo-suppression (67.21%) than F1 (63.94%), F2 (6.99%), F3 (2.81%), and F4 (37.3%). At 12.5 mg/kg bw, F5 suppressed P. berghei by 91.09%, surpassing chloroquine (87.79%), and restored altered hematological indices and CD4+ counts. Compounds identified in F5 included caffeate, linalool, terpinene-4-ol, quinovic acid, quercetin, prosopinine, catechin, and apigeninin. In conclusion, the fraction F5 of P. africana stem bark exhibited higher antimalarial activity than chloroquine and the identified compound might likely contribute to its activity.

LC-MS analysis of Urtica urens water extracts: active ingredients and their impact on beta-hematin formation

This study investigates the potential antimalarial efficacy of aqueous extracts from various parts of dwarf nettle (Urtica urens)-leaves, roots, and stems-by examining their ability to inhibit beta-hematin formation. The findings indicate that extracts from the roots and stems exhibit minimal antimalarial activity, while the leaf extracts show considerable promise. When the leaf extract was diluted, it maintained its antimalarial activity at concentrations up to 50%, but effectiveness decreased with further dilution. This decline may be attributed to the reduced concentrations of the active compounds present in the water extracts. The leaf extract was effective at concentrations ranging from 1 mg/ml to 0.5 mg/ml, but lost its activity at 0.3 mg/ml, likely due to inadequate levels of these compounds at this level. LC-MS analysis identified key flavonoids in the leaf extract, including flavanols such as Myricetin 3-O-rutinoside, Isorhamnetin 3-O-glucoside 7-O-rhamnoside, Kaempferol 3,7-diglucoside, Kaempferol-3-O-rutinoside, Rutin, Apigenin 7-O-diglucuronide, Kaempferol 3-O-(6''-acetyl-galactoside) 7-O-rhamnoside and flavanones such as Luteolin 7-O-diglucuronide. Examining their chemical structures offers insights into how these flavonoids might interact with heme, thereby enhancing our understanding of their antimalarial potential and supporting their consideration as candidates for malaria therapy.

Experimental and computational evaluation of anti-malarial and antioxidant potential of transition metal (II) complexes with tridentate schiff base derived from pyrrolopyrimidine.

In the twenty-first century, we are experiencing persistent waves of diverse pathogen variations, contributing significantly to global illness and death rates. Within this varied spectrum of illnesses, malaria and oxidative damage emerge as prominent obstacles that have persistently affected human health. The motivation for exploring the antioxidant potential of transition metal (II) complexes with tridentate Schiff base ligands is driven by the need for effective treatments against malaria and oxidative stress-related conditions. Both malaria and oxidative damage are significant global health concerns. Transition metal complexes can potentially offer enhanced anti-malarial and antioxidant activities, providing a dual benefit. To explore the aforementioned facts and examine the therapeutic potential, the previously synthesized pyrrolopyrimidinehydrazide-3-chlorobenzaldehyde, such as HPPHmCB ligand(1)andtheirMn(II),Fe(II),Co(II),Ni(II), Pd(II),Cu(II),Zn(II),Cd(II),Hg(II)complexes(2-10) of benzaldehydes and pyrrolopyrimidinehydrazide were proposed for in vitro anti-malarial and antioxidant investigation. These compounds were assessed for their anti-malarial efficacy against Plasmodium falciparum using a micro assay protocol, with IC50 values indicating the concentration required to inhibit parasite maturation by 50%. The Hg(II) complex displays pronounced antimalarial activity with an IC50 value of 1.98 ± 0.08µM, closely aligning with the efficacy of quinine, whereas Zn(II), Cu(II), Pd(II) complexes demonstrates most significant anti-malarial activity, with IC50 values close to the reference compound quinine. The antioxidant activity of the compounds was evaluated using the DPPH assay, with several metal complexes such as Cu(II)and Zn(II) showing strong potential in neutralizing oxidative stress. Furthermore, molecular docking simulations were conducted to explore the binding interactions of the compounds with PfNDH2, providing insights into their pharmacological potential. The study also examined the electronic properties, solubility, and potential hepatotoxicity of the compounds. The findings suggest that the metal complexes could be promising candidates for further development as anti-malarial agents, offering enhanced potency compared to the base compound.

Design, Synthesis, and Evaluation of Imidazole Derivatives as Potential Antimalarial Drugs

Design, Synthesis, and Evaluation of Imidazole Derivatives as Potential Antimalarial Drugs

Bioassay-directed isolation of antiplasmodial alkaloids and lignans from the dry seeds of Piper guineense Schumach. & Thonn. (Piperaceae) and their cytotoxicity

The identification of antiplasmodial lead compounds from the dry seeds of Piper guineense has been performed using a bioassay-directed protocol. Briefly, its methanolic seeds extract has been suspended in water and partitioned using n-hexane, dichloromethane, ethyl acetate and n-butanol to afford four main fractions A−D which were further submitted to antiplasmodial assay against Plasmodium falciparum 3D7. The bioassay results showed that its dichloromethane-soluble fraction has the highest potency with 31.8 % of the parasite P. falciparum 3D7 survival. The purification of the active fraction with successive column chromatography led to the isolation and identification of eleven compounds including six piperine-type amides (1−6), two lignans (7 and 8), one fatty acid (9), and two steroids (10 and 11). The antiplasmodial assay of compounds 1−8 against the two strains Pf 3D7 and Pf Dd2 showed that only the alkaloids 1−6 displayed moderate potencies with the highest IC50 values of 17.4 ± 0.7 µg/mL (for 6 against Pf 3D7) and 14.6 ± 0.3 µg/mL (for 2 against Pf Dd2). Furthermore, the cytotoxicity of the tested compounds against Vero cell lines showed that only compounds 5 and 6 displayed a cytotoxicity with CC50 values of 335.4 ± 7.6 µg/mL and 151.8 ± 2.4 µg/mL, respectively, while their selectivity index limits an acceptable range. The results support the use of the plant in folk medicine for handling malaria, and demonstrate that piperine-type amides are responsible for the antiplasmodial activity of P. guineense and are good leads in the development of safe and potent antimalarial drugs.