Antimalarial Efficacy Research Articles

Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda

Antimalarial therapeutic efficacy studies are vital for monitoring drug efficacy in malaria-endemic regions. The WHO recommends genotyping polymorphic markers including msp-1, msp-2, and glurp for distinguishing recrudescences from reinfections. Recently, WHO proposed replacing glurp with microsatellites (Poly-α, PfPK2, TA1). However, suitable combinations with msp-1 and msp-2, as well as the performance of different algorithms for classifying recrudescence, have not been systematically assessed. This study investigated various microsatellites alongside msp-1 and msp-2 for molecular correction and compared different genotyping algorithms across three sites in Uganda. Microsatellites 313, Poly-α, and 383 exhibited the highest diversity, while PfPK2 and Poly-α revealed elevated multiplicity of infection (MOI) across all sites. The 3/3 match-counting algorithm classified significantly fewer recrudescences than both the ≥ 2/3 and Bayesian algorithms at probability cutoffs of ≥ 0.7 and ≥ 0.8 (P < 0.05). The msp-1/msp-2/2490 combination identified more recrudescences using the ≥ 2/3 and 3/3 algorithms in the artemether-lumefantrine (AL) treatment arm, while msp-1/msp-2/glurp combination classified more cases of recrudescence using the ≥ 2/3 in the dihydroartemisinin-piperaquine (DP) arm. Microsatellites PfPK2 and Poly-α, potentially sensitive to detecting minority clones, are promising replacements for glurp. Discrepancies in recrudescence classification between match-counting and Bayesian algorithms highlight the need for standardized PCR correction practices.

Exploring Quinoline Derivatives: Their Antimalarial Efficacy and Structural Features

Objectives: Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effectiveness and structural characteristics of quinoline-based compounds as antimalarial agents. It specifically focuses on their therapeutic effects as well as potential prospects for exploring structure-activity relationship (SAR). In addition, this study aims to identify lead compounds that can efficiently battle multidrug-resistant forms of Plasmodium falciparum and Plasmodium vivax. Methods: A comprehensive review was conducted to evaluate the effectiveness of quinoline-based antimalarial medications in eradicating P. falciparum and P. vivax. The mechanism of action and SAR of these compounds were analyzed Results: Quinoline-based antimalarials demonstrated significant effectiveness in eliminating P. falciparum parasites, particularly in regions severely impacted by malaria, including Africa and Asia. These compounds were found to exhibit tolerance and immune-modulating properties, indicating their potential for more widespread utilization. The investigation identified various new quinoline compounds with improved antimalarial activity, including metal-chloroquine complexes, diaminealkyne chloroquines, and cinnamoylated chloroquine hybrids. This study explored different mechanisms by which these compounds interact with parasites, including their ability to accumulate in the parasite’s acidic food vacuoles and disrupt heme detoxification. The derivatives demonstrated strong efficacy against chloroquine-resistant strains and yielded positive results. Conclusion: Quinoline-based compounds represent a promising avenue for combating malaria due to their demonstrated efficacy against P. falciparum and P. vivax parasites. Further research on their mechanisms of action and SAR could lead to the development of more effective antimalarial medications.

Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential.

Malaria, caused by Plasmodium species and transmitted by Anopheles mosquitoes, continues to pose a significant global health threat. Pipecolisporin, a cyclic hexapeptide isolated from Nigrospora oryzae, has emerged as a promising antimalarial candidate due to its potent biological activity and stability. This study explores the synthesis, antimalarial activity, and computational studies of pipecolisporin, aiming to better understand its therapeutic potential. The peptide was successfully synthesized using Fmoc-based solid-phase peptide synthesis (SPPS) followed by cyclization in solution. The purified compound was characterized using HPLC and mass spectrometry, confirming a molecular ion peak at m/z [M + H]+ 692.4131, which matched the calculated mass. Structural verification through 1H- and 13C-NMR demonstrated strong alignment with the natural product. Pipecolisporin exhibited significant antimalarial activity with an IC50 of 26.0 ± 8.49 nM, highlighting its efficacy. In addition to the experimental synthesis, computational studies were conducted to analyze the interaction of pipecolisporin with key malaria-related enzymes, such as dihydrofolate reductase, plasmepsin V, and lactate dehydrogenase. These combined experimental and computational insights into pipecolisporin emphasize the importance of hydrophobic interactions, particularly in membrane penetration and receptor binding, for its antimalarial efficacy. Pipecolisporin represents a promising lead for future antimalarial drug development, with its efficacy, stability, and binding characteristics laying a solid foundation for ongoing research.

Low prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola

BackgroundMalaria is the parasitic disease with the highest global morbidity and mortality. According to estimates from the World Health Organization (WHO), there were around 249 million cases in 2022, with 3.4% occurring in Angola. The emergence and spread of drug-resistant Plasmodium falciparum have compromised anti-malarial efficacy and threatens malaria elimination campaigns using artemisinin-based combination therapy (ACT). Increased copy number (CNV) of the P. falciparum gene plasmepsin 2 (pfpm2) have been reported to confer parasite tolerance to piperaquine (PPQ) and the multidrug resistance-1 (pfmdr1), resistance to mefloquine (MEF) and decreased susceptibility to lumefantrine (LUM). PPQ, MEF and LUM are ACT partner drugs. Therefore, CNV detection is a useful tool to track ACT resistance risk. The potential for future treatment failure of artemisinin-based combinations (that include PPQ, LUM and AMQ), due to parasite resistance in the region, emphasizes the need for continued molecular surveillance.MethodsOne hundred and nine clinically derived samples were collected at Hospital Central Dr. António Agostinho Neto (HCL) in Lubango, Angola. qPCR targeting the small-subunit 18S rRNA gene was used to confirm P. falciparum infection. Copy number estimates were determined using a SYBR green-based quantitative PCR assay.ResultsOverall, this study revealed a low number of resistance CNVs present in the parasite population at Lubango, for the genes pfmdr1 and pfpm2. Of the 102 samples successfully analysed for pfpm2 10 (9.8%) carried increased CNV and 9/101 (8.9%) carried increased CNV of pfmdr1.ConclusionsThis study provides, for the first time, evidence for the presence of CNVs in the pfpm2 and pfmdr1 genes in P. falciparum isolates from southern Angola.

Efficacy and Safety of Antimalarial as Repurposing Drug for COVID-19 Following Retraction of Chloroquine and Hydroxychloroquine.

Various repurposing drugs have been tested for their efficacy on coronavirus disease 2019 (COVID-19), including antimalarial drugs. During the pandemic, Chloroquine (CQ) and Hydroxychloroquine (HCQ) demonstrated good potential against COVID-19, but further studies showed both drugs had side effects that were more dangerous than the efficacy. This made World Health Organization (WHO) ban the usage for COVID-19 patients. In this context, there is a need to explore other antimalarial drugs as potential therapies for COVID-19. This study provides a descriptive synthesis of clinical trials evaluating antimalarial drugs for COVID-19 treatment conducted after the withdrawal of CQ and HCQ. The method was a literature study using the keywords "antimalarial", "COVID-19", "SARS-CoV-2", "clinical trial", and "randomized controlled trial" on the MEDLINE, Scopus, and Cochrane databases. Inclusion criteria were published clinical trials with randomized controlled trials (RCTs) on the efficacy and safety of single antimalarial drugs for COVID-19, published in English and excluding combination therapies. The results showed 3 antimalarial drugs, namely Quinine Sulfate (QS), Atovaquone (AQ), and Artemisinin-Piperaquine (AP), had gone through clinical trial to assess efficacy and safety against COVID-19 patients. Out of the 3 drugs, only AP showed significant results in the primary outcome, which was the time required to reach undetectable levels of SARS-CoV-2. Furthermore, the intervention group took 10.6 days, and the control group took 19.3 days (p=0.001). Based on this review, AP showed significant potential as a therapy in the fight against COVID-19.

In-vivo Anti-Plasmodial Activity of Enantia chlorantha: A Potential Plasmodium berghei Survival Inhibitor

The emergence of resistance to existing antimalarial drugs has intensified the search for novel, effective, and affordable treatments for malaria. The sensitivity of strains of Plasmodium spp. to the commonly known antimalarial drugs over time undermines the effectiveness of treatment. Enantia chlorantha, traditionally used in African folk medicine, has shown potential antimalarial agents that inhibit parasite survival and growth. This study aimed to investigate the antimalarial efficacy of Enantia chlorantha extracts on Plasmodium berghei using in vivo approach. A total of 55 albino mice randomized into 5 groups were inoculated with an infection of 1.0 x 107 chloroquine sensitive strain of Plasmodium berghei intra-peritoneally. Methanol, n-hexane and ethyl acetate extracts of Enantia chlorantha stem-bark was extracted successfully using a Sohxlet extractor. Experimental mice were treated orally with doses of 5mg/kg, 10mg/kg, and 20mg/kg of each plant extract (EC2, EEA and EHEX treated groups), a dose of 10mg/kg chloroquine (standard control group), and a dose of 0.2ml Olive Oil (negative control group). The level of parasitaemia and death per day were used to assess the chemosuppressive effect and survival rate of the extracts. Data were analyzed using One Way Analysis of variance ANOVA followed by post hoc test, and were expressed as mean ± standard error of mean (M ± SEM), and percentage. All analyses were carried out at a 95% confidence interval, with a significance level set at P &lt; 0.05. The treatment with various concentrations of Enantia chlorantha extracts (EC2, EEA, and EHEX) significantly reduced parasitaemia levels, with higher doses showing greater suppression. EC2 reduced parasitaemia from 1.00% (5 mg/kg) to 0.71% (20 mg/kg) with p=0.0003, while EEA reduced it from 1.15% (5 mg/kg) to 0.57% (20 mg/kg) with p=0.0028. EHEX showed a suppression from 1.09% (10 mg/kg) to 0.46% (20 mg/kg) with p=0.0001. Chemosuppression in EC2, EEA, and EHEX increased with dosage, with EEA at 20 mg/kg surpassing chloroquine in chemosuppression (85.64% vs. 69.86%, p=0.0009). In survival outcomes, EC2, EEA, and EHEX exhibited dose-dependent increases in survival index, with EEA at 20 mg/kg reaching 90%, but none matched chloroquine's 100% survival, Enantia chlorantha extracts particularly EEA significantly reduced parasitaemia level and increased chemosuppressive effect and survival index at high doses, indicating the potent antimalarial activity of Enantia chlorantha.

Exploring the potential antimalarial properties, safety profile, and phytochemical composition of Mesua ferrea Linn.

The increased resistance of Plasmodium falciparum to artemisinin and its partner drugs poses a serious challenge to global malaria control and elimination programs. This study aimed to investigate the therapeutic potential of Mesua ferrea Linn., a medicinal plant, as a source for novel antimalarial compounds. In this study, we conducted in vitro assays to evaluate the antimalarial activity and cytotoxicity of crude extracts derived from M. ferrea L. leaves and branches. Subsequently, the most promising extracts were subjected to assessments of their antimalarial efficacy and acute oral toxicity tests in mouse models. Furthermore, selected crude extracts underwent gas chromatography-mass spectrometry (GC-MS) analysis to identify their phytochemical compositions. Our findings revealed that the ethanolic extract of M. ferrea L. branches (EMFB) exhibited high antimalarial activity, with an IC50 value of 4.54 μg/mL, closely followed by the ethanolic extract of M. ferrea L. leaves (EMFL), with an IC50 value of 6.76 μg/mL. Conversely, the aqueous extracts of M. ferrea L. branches (AMFB) and leaves (AMFL) exhibited weak and inactive activity, respectively. The selected extracts, EMFB and EMFL, demonstrated significant dose-dependent parasitemia suppression, reaching a maximum of 62.61% and 54.48% at 600 mg/kg body weight, respectively. Furthermore, the acute oral toxicity test indicated no observable toxicity at a dosage of 2,000 mg/kg body weight for both extracts. GC-MS analysis revealed abundant compounds in the EMFB, such as oleamide, cis-β-farnesene, alloaromadendrene, physcion, palmitic acid, 5-hydroxymethylfurfural, and 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-, while the EMFL contained friedelin, friedelinol, betulin, β-caryophyllene, oleamide, and 5-hydroxymethylfurfural. Notably, both extracts shared several phytochemical compounds, including 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-, 5-hydroxymethylfurfural, α-copaene, cyperene, β-caryophyllene, alloaromadendrene, palmitic acid, ethyl palmitate, and oleamide. Additionally, further study is needed to isolate and characterize these bioactive compounds from M. ferrea L. leaves and branches for their potential utilization as scaffolds in the development of novel antimalarial drugs.

Docking-Based Virtual Screening to Identify the Cysteine Protease Falcipain-2 Inhibitors of Plasmodium falciparum

Malaria is an infectious disease caused by Plasmodium protozoan parasites that transmit via the female Anopheles sp. mosquito. Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi are the five Plasmodium species known to infect humans. P. falciparum is the most virulent species, causing the most deaths worldwide. The decrease in efficacy of most antimalarials suggests drug resistance. Therefore, the development of new effective antimalarials, particularly against novel targets, was still required. Cysteine protease falcipain-2 (CPF-2) plays a role in hemoglobin degradation; therefore, inhibiting the activity of this enzyme could be a viable antimalarial target. This study aimed to identify a potential inhibitor for the CPF-2 with PDB ID 3BPF from the ZINC15 database for treating malaria. This study employs a virtual screening workflow with HTVS, SP, and XP docking methods on the Glide Maestro Schrodinger. Based on the glide XP docking score, 10 hit compounds were identified, and their conformational interactions with CPF-2 were compared to the natural ligand (E-64). The binding energy values of hit compounds vary from -7.131 kcal/mol to -8.074 kcal/mol, which is more negative than the E-64 (-6.011 kcal/mol). The three best compounds identified from the ZINC15 database are ZINC000025691540, ZINC000096436101, and ZINC000097797430. All the hit compounds discovered similar interaction with E-64, specifically on the CPF-2 binding pocket residues with Gln36, Cys42, Gly83, Asn173, and His174. All hit compounds exhibit suitable Lipinski rule profiles and are potentially evaluated experimentally as CPF-2 enzyme inhibitor candidates. Keywords: cysteine protease falcipain-2, malaria, molecular docking, Plasmodium falciparum, virtual screening

Genotyping and Characterizing Plasmodium falciparum to Reveal Genetic Diversity and Multiplicity of Infection by Merozoite Surface Proteins 1 and 2 (msp-1 and msp-2) and Glutamate-Rich Protein (glurp) Genes.

Resistance to current antimalarial drugs is steadily increasing, and new drugs are required. Drug efficacy trials remain the gold standard to assess the effectiveness of a given drug. The World Health Organization (WHO)'s recommendation for the optimal duration of follow-up for assessing antimalarial efficacy is a minimum of 28 days. However, assessing antimalarial drug efficacy in highly endemic regions can be challenging due to the potential risks of acquiring a new infection in the follow-up period, and thus, it may underestimate the efficacy of the given drugs. A new treatment should be introduced if treatment failure rates exceed 10%. Overestimation occurs as a result of retaining a drug with a clinical efficacy of less than 90% with increases in morbidity and mortality, while underestimation may occur due to a misclassification of new infections as treatment failures with tremendous clinical and economic implications. Therefore, molecular genotyping is necessary to distinguish true new infections from treatment failures to ensure accuracy in determining antimalarial efficacy. There are three genetic markers that are commonly used in antimalarial efficiency trials to discriminate between treatment failures and new infections. These include merozoite surface protein 1 (msp-1), merozoite surface protein 2 (msp-2), and glutamate-rich protein (glurp). The genotyping of P. falciparum by nested polymerase chain reaction (n-PCR) targeting these markers is discussed with the inherent limitations and uncertainties associated with the PCR technique and limitations enforced by the parasite's biology itself.

Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria

BackgroundMalaria, a tropical neglected disease, imposes a significant burden on global health, leading to the loss of thousands of lives annually. Its gold standard treatment is a combination therapy of lumefantrine (LUM) and artemether (ART). Nanotechnology holds significant potential for improving drug bioavailability and potency while reducing adverse effects.ObjectivesThis study aimed to develop lipid-core nanocapsules containing ART and LUM and evaluate their effects in an experimental cerebral malaria model (ECM).MethodsThe polymeric interfacial deposition method was used to develop lipid-core nanocapsules (LNCs) containing ART and LUM (LNCARTLUM) and were characterized using micrometric and nanometric scales. Male C57BL/6 mice were infected with Plasmodium (P.)berghei ANKA (PbA, 1 × 105 PbA-parasitized red blood cells, intraperitoneally). On day 5 post-infection, PbA-infected mice were orally administered with ART + LUM, LNCARTLUM, blank nanocapsules (LNCBL), or ethanol as a control. Parasitemia, clinical scores, and survival rates were monitored throughout the experiment. Organ-to-body weight ratios, cytokine quantification, and intravital microscopy analyses were conducted on day 7 post-infection.ResultsLNCs were successfully developed and characterized. The treatment with LNCARTLUM in ECM resulted in complete clearance of parasitemia at 10 dpi, decreased clinical scores, and maintained 100% survival rates. Thereated mice exhibited splenomegaly and reduced TNF-α, IL-1β, and MCP1 levels in the brain. Furthermore, the LNCARTLUM treatment protected the brain microvasculature, reducing the number of cells in the rolling process and adherent to the microvasculature endothelium.ConclusionNanoformulations can potentially improve the efficacy of antimalarial drugs and be considered a promising approach to treat malaria.

Optimization of in vivo antimalarial efficacy of combinations of aqueous leaf extracts of Artemisia annua L., Vernonia amygdalina Del, and Microglossa pyrifolia (Lam.) Kuntze using factorial design

BackgroundMalaria continues to be among the leading causes of mortality in Africa including Uganda, with the emergence of parasite resistance to the first-line therapeutics (Artemisinin- based Combination Therapy). To find new therapeutics, this study has reported an in vivo antimalarial efficacy of combinations of Artemisia annua (Aa), Vernonia amygdalina (Va), and Microglossa pyrifolia (Mp) in mice model using factorial design.MethodsThe Aa and Va were extracted by hot infusion, and Mp by cold maceration using distilled water. The dry extracts were screened for different phytochemicals, and later subjected to in vivo antimalarial activity using Peter’s 4-day suppressive test. The 23 factorial design used Aa, Va, and Mp aqueous extracts as independent variables at two levels (-1 and 1), and the percentage chemo suppression and survival time as response variables. The data was analyzed using Design Expert 13 and GraphPad Prism employing ANOVA linear regression modelling and t-test respectively.ResultsAll the extracts had alkaloids, phenols, saponins, terpenoids, cardiac glycosides, tannins, steroids, and carbohydrates. The various combinations showed chemo suppression from 41.5 to 91.0% and survival time of 19 to 23 days. The first three combinations having lower levels of Aa (200 mg/kg) exhibited higher chemo suppression (> 90%) compared to Artemisinin-Lumefantrine positive control at 4 mg/kg with 87.5%. Lower levels of Aa in the combinations contributed to high chemo suppression while higher levels of Va prolonged survival times. Interactions between Aa and Mp showed higher chemo suppression, and that between Aa and Va increased survival time. An optimized prediction of 94.4% chemo suppression was made by the ANOVA model at lower levels of Aa and Va, and a higher level of Mp, which is similar to an experimental run which gave a response of 90. 6%.ConclusionAn optimum combination of the three plants as a natural herbal antimalarial therapy was obtained using factorial design, and it offers an alternative to first line Artemisinin based Combination Therapy (ACTs) as parasite resistance looms. This combination could be further developed into a standard phytopharmaceutical and subjected to Randomized Controlled Trials (RCTs).

Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles.

Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release percentage of MA from MA-PCL@PDA-NPs was considerably higher in phosphate buffer with 10 mM GSH at pH 5.5 (88.10%) than in phosphate buffer without GSH at pH 7.4 (16.98%). The green fluorescence within iRBCs of coumarin 6, the probe of NPs (C6-PCL@PDA-NPs), could be reduced significantly after adding the NPP inhibitor furosemide (p < 0.001), which demonstrated that MA-PCL@PDA-NPs could be ingested into iRBCs through NPPs. In vivo antimalarial pharmacodynamics in Plasmodium berghei K173-bearing mice showed that the inhibition ratio of MA-PCL@PDA-NPs (93.96%) was significantly higher than that of commercial artesunate injection (AS-Inj, 63.33%). The above results showed that the developed MA-PCL@PDA-NPs possessed pH-GSH dual-responsive drug release characteristics and targeting efficacy for iRBCs, leading to higher antimalarial efficacy against Plasmodium.

Over fifteen years of chloroquine withdrawal in Nigeria: a qualitative investigation into the execution of this policy by healthcare providers and amongst patients in a rural community.

Background Chloroquine (CQ) was once an important drug used in malaria treatment especially due to its affordability, ease of use and high anti-malarial efficacy. However, it was withdrawn from clinical practice in Nigeria in 2005 following a widespread of resistance cases reported in the public health domain. This study aims to ascertain the level of compliance with the policy on CQ withdrawal among patients, Patent and proprietary medicine vendors (PPMVs), Pharmacists and Physicians. Method A cross-sectional survey involving both online and offline data collection was carried out. A total of 582 participants were recruited and consisted of patients (N = 300), PMVs (N = 94), Physicians (N = 94), and Pharmacists (N = 94). Patients spanned across health services at primary health centers and hospitals in the Anaocha community. Result Our findings show that the patients were equally aware of what CQ is used for (χ² = 7.071, p = 0.215). However, significant disparities were observed in the knowledge, attitude, and perception of CQ resistance and its continual use among health professionals and PPMVs (χ² = 160.54 and 158.54, p = 0.000). Additionally, despite the chloroquine withdrawal policy in Nigeria, there was evident non-compliance among majorly PPMVs and other healthcare professionals. A few of patients continued to utilize CQ for malaria treatment and PPMVs were mostly likely to prescribe and stock CQ. Conclusion The study revealed that chloroquine use in Nigeria is still sustained notwithstanding the switch in the antimalarial drug policy from chloroquine to ACTs in 2005. Feasible implementation strategy through awareness program and campaign especially in the primary health centers across Nigeria and through associations such as Nigeria Association of Patent and Proprietary Medicine Dealers (NAPPMED), Pharmaceutical Society of Nigeria (PSN) and Nigeria Medical Association (NMA) is recommended.

Genotyping methods to distinguish Plasmodium falciparum recrudescence from new infection for the assessment of antimalarial drug efficacy: an observational, single-centre, comparison study

Distinguishing Plasmodium falciparum recrudescence from new infections is crucial for the assessment of antimalarial drug efficacy against Pfalciparum. We aimed to compare the efficacy of different genotyping methods to assess their effect on drug efficacy estimates, particularly in patients from high-transmission settings with polyclonal infections. In this head-to-head comparison study, we compared five different genotyping methods currently used: fast capillary electrophoresis (F-CE) using msp1, msp2, and glurp; high-resolution capillary electrophoresis (H-CE) using msp1, msp2, and glurp; H-CE using microsatellites; targeted amplicon deep sequencing (TADS) using single nucleotide polymorphism (SNP)-rich markers; and high-resolution melting (HRM) analysis using msp1 and msp2. We assessed their sensitivity in detecting minority clones in polyclonal infections, their reproducibility, and the genetic diversity of the markers used. Our study used four well characterised Pfalciparum laboratory strains mixed in varying ratios, and 20paired samples collected from an in-vivo clinical trial. The experiments were performed at the Swiss Tropical and Public Health Institute in Basel, Switzerland between May 5, 2020, and Aug 23,2021. H-CE using msp1 and msp2 and TADS revealed the highest sensitivity in detecting minority clones (up to ratios of 1:100 for H-CE and 50:1:1:1 for TADS in the FCB1:HB3 and 3D7:K1:HB3:FCB1 laboratory strain mixtures, respectively), highest reproducibility (intra-assay: 99% and 91% for H-CE and TADS, respectively; inter-assay: 98% and 92% for H-CE and TADS, respectively), and highest genetic diversity in the used markers (up to 36and32unique genotypes in 20paired samples for H-CE using msp2 and TADS using cpmp, respectively). Microsatellites assessed by H-CE had a lower genetic diversity compared with msp1, msp2, and glurp assessed by H-CE and the SNP-rich markers assessed by TADS, with a maximum of 13unique genotypes, and some genotypes having allelic frequencies larger than 30%.Markers used by TADS gave the most consistent results in distinguishing recrudescence from new infection across all methods (in 18of 20pairs of samples vs 15of 20pairs for H-CE). WHO currently recommends replacing glurp with microsatellites. However, in this study, the replacement of glurp with microsatellites did not change the genotyping outcome, probably due to the lower genetic diversity of microsatellites. More studies with large sample sizes are required to identify the most suitablemicrosatellites that could replace glurp. Our study indicates that TADS should be considered the gold standardfor genotyping to distinguish recrudescence from new infection, and that it should be used to validate other methods. Swiss Tropical and Public Health Institute.

Integrating schiff base ligands with diorganotin(IV) metal: Crystallographic insights and biological potency against malaria and oxidative stress

Amidst the ongoing search for potent antimalarial agents, this research focuses on synthesizing and analyzing diorganotin(IV) complexes (3–10) with Schiff base ligands (1–2) derived from 2-amino-4‑tert-butylphenol and salicylaldehyde derivatives, revealing compelling medicinal applications. Comprehensive structural characterization of these compounds was conducted using a suite of analytical techniques, including FT-IR, NMR (1H, 13C and 119Sn), SEM-EDAX, TGA and mass spectrometry. These analyses unequivocally confirmed that the ligands coordinate to the diorganotin(IV) ion via oxygen and nitrogen donor sites in an iminol configuration, indicating a pentacoordinated stereochemistry. Furthermore, to confirm the complexes structural characteristics, SC-XRD was performed on the complex 7 [Me₂SnL2] which indicated that the compound crystallizes in a monoclinic system with distorted square pyramidal stereochemistry. Biological evaluations states that the complexes have superior biological activities compared to their respective ligands with the order of activity being: Ph2SnL1–2>Bu2SnL1−2>Et2SnL1−2>Me2SnL1−2. Complexes (6, 10) showed significant antimalarial and antioxidant efficacy, with IC50 values of 0.99 ± 0.18 - 1.69 ± 0.15 µM and 2.36 ± 0.05 - 3.16 ± 0.02 µM, respectively, comparable to standard therapeutic agents. ADMET lab 2.0 evaluation confirmed their adherence to Lipinski's Rule of Five and strong pharmacokinetic properties, including oral bioavailability, permeability and clearance, similar to standard drugs.

An Investigation on Optical, Larvacidal and Cytotoxicity Analysis of Sulfanilic Acid Single Crystal for Optical and Biomedical Applications.

Sulfanilic acid (SFA) crystal is well known as an effective material for photonic, electro-optical, harmonic generating and biomedical applications. A well-known nonlinear optical material, a high-quality SFA single crystal made utilizing the slow evaporation solution method (SEST) is the subject of this article. A 75 days development period yielded a transparent SFA single crystal measuring 5 × 5 × 2 mm3. The grown crystal used for different characterizations like Single crystal XRD used to find out the cell parameters. Fourier transforms infrared utilized to identify the band assignments. UV-Visible analysis used to detect the absorbance of the crystal and it is utilized for optical application. Photoluminescence studies utilized to recognize the excitation and emission of the grown crystal. Fluorescence used for determining the crystallinity and purity of the sample. The quantitative analysis is verified by using Elemental Dispersive Analysis by X-Rays. Scanning Electron Microscopy utilized to identify the structural and morphological characteristics. To the best of our knowledge, this paper is the first to provide the generated crystal that was used to analyze cytotoxicity and larvacidal activity. Assessment of larvicidal activity was used to ascertain the anti-malarial efficacy. We tested the items on MCF7-Human Breast cancer cell line and MCF7 Vero cells using the MTT Assay to identify the molecular basis of their cytotoxicity in vitro. Biological and optical are two areas that could benefit from the created crystal.

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.

Nanotechnology in Malaria Treatment: Targeted Drug Delivery Systems and Future Applications

Malaria continued to be a major global health challenge, particularly in regions with high disease burden, despite advancements in treatment options such as Artemisinin-based Combination Therapies (ACTs). The emergence of nanotechnology offered a transformative approach to malaria treatment, with its potential to improve drug delivery, bioavailability, and therapeutic outcomes. This review examined the current applications and advancements in nanotechnology for malaria treatment, focusing on the use of nanocarriers like liposomes, polymeric nanoparticles, and solid lipid nanoparticles. These systems enhanced the efficacy of antimalarial drugs by enabling targeted delivery to malaria-infected cells, overcoming drug resistance, and offering controlled release mechanisms. The review also explored emerging strategies such as combination therapies, personalized nanomedicine, responsive nanoparticles, and vaccine delivery systems. While nanotechnology holds great promise, challenges including safety, scalability, regulatory hurdles, and cost were addressed. Future directions suggest innovations such as smart nanocarriers, personalized treatments, and enhanced diagnostic integration. Methodologically, this review synthesized data from recent preclinical and clinical research to provide a comprehensive analysis of nanotechnology’s role in advancing malaria treatment. Global collaboration and interdisciplinary research will be pivotal in realizing the full potential of nanotechnology in combating malaria. Keywords: Nanotechnology, malaria treatment, drug delivery systems, liposomes, nanoparticles, targeted therapy, drug resistance

Unveiling Anti-Malarial, Antimicrobial, Antioxidant Efficiency and Molecular Docking Study of Synthesized Transition Metal Complexes Derived From Heterocyclic Schiff Base Ligands.

Malaria, a persistent and ancient adversary, continues to impact vast regions worldwide, afflicting millions and severely affecting human health and well-being. Recently, despite significant progress in combating this parasitic disease, malaria remains a major global health concern, especially in areas with limited resources and vulnerable populations. Consequently, identifying and developing effective agents to combat malaria and its associated dysfunctions is essential therefore the two new Schiff base ligands incorporated Co(II), Ni(II), Cu(II) and Zn(II) ions were synthesized and thoroughly characterized. The synthesized compounds were assessed for in vitro anti-malarial and antimicrobial efficacy, compounds (9, 10) demonstrated highest potential with IC50=1.08±0.09 to 1.18±0.04 μM against P. falciparum and MIC=0.0058 μmol/mL against C. albicans and E. coli, respectively. The complexes (5, 6) were effectively reduce mitigate oxidative stress with lowest IC50 value of 2.69±0.12 to 2.87±0.09 μM. Moreover, the biological findings were reinforced by a molecular docking investigation involving the potential compounds (2, 7-10) against dihydroorotate dehydrogenase and sterol 14-alpha demethylase proteins which exposed complex's excellent biological response than their parent ligands. ADMET profiling was used to confirm the compounds' oral drug-like features. This research offers promising prospects for future multi-functional drug innovations targeting malaria, pathogenic infections, and oxidative stress.