Antimalarial Effects Research Articles

Biological Potential and Therapeutic Effectiveness of Artemetin from Traditional to Modern Medicine: An Update on Pharmacological Activities and Analytical Aspects.

Plant products derived from natural sources have been used in medicine as a raw material and newer kinds of drug molecules in pharmaceuticals and other allied health sectors. Phytochemicals have numerous medicinal potentials, including anti- ageing, anti-carcinogenic, anti-microbial, anti-oxidant, and anti-inflammatory activity in medicine. Development and biological application of herbal products in modern medicine signified the value of traditional medicinal plants in health care systems. The objective of the present study was to explore the scientific knowledge of the medicinal importance and therapeutic potential of artemetin in medicine. However, scientific investigations for their pharmacological activities in medicine have been done through scientific data analysis of different scientific research work collected from PubMed, Google, Science Direct and Google Scholar in order to know the biological importance of artemetin in medicine. Moreover, analytical data of artemetin have also been discussed in the present work. The present work and scientific data signified the biological potential of artemetin in medicine. Artemetin has been derived from numerous medicinal plants and dietary herbs, including Artemisia absinthium, Artemisia argyi, Achillea millefolium, and Vitex trifolia. Artemetin has anti-malarial, anti-oxidant, anti-apoptotic, anti-microbial, antitumoral, anti-atherosclerotic, anti-inflammatory, hypotensive and hepatoprotective effects. Further, the biological role of artemetin on lipid oxidation, cytokine production, lipoxygenase, and estrogen-like effects was also investigated in the present work. Analytical data on artemetin in the present paper signified their important role in the isolation, separation, and identification of different classes of pure phytochemicals, including artemetin in medicine. Scientific data analysis of artemetin signified its therapeutic potential in medicine for the development of newer scientific approaches for different human disorders.

Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in Plasmodium berghei-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling

Objectives: Investigating how nanoparticle systems interact in whole blood (WB) is critical to evaluating the effectiveness of malaria therapy. Methods: We decided to establish a pharmacokinetic/pharmacodynamic (PK/PD) model of the quinine population in WB using Plasmodium berghei-infected mice, with a subsequent model comparison for nanocapsules coated with polysorbate (NCP80) or prepared with Eudragit® RS (NCEUD). The WB quinine population pharmacokinetic model in rats was developed using plasma and partition coefficients for rat erythrocytes. Mouse WB quinine population PK/PD modeling was developed using allometrically scaled literature-free mouse quinine pharmacokinetic data and covariate values to obtain a WB population pharmacokinetic model for quinine and nanocapsules in mice. This allowed for PK/PD modeling of the quinine population with the WB concentration and parasitemia data in mice. All models were built in NONMEN. Results: The WB quinine concentration profiles in rats were characterized using a two-compartment model. Nanoencapsulation reduced clearance and central compartment volume and increased peripherical compartimental volume. A maximum effect model described the PK/PD of the quinine WB population in mice, demonstrating that NCEUD enhances the antimalarial effect. Conclusions: Quinine WB is a good surrogate for describing the response to exposure in malaria. NCEUD outperformed NCP80 and free quinine, suggesting that cationic surfaces improve the potential for treating malaria.

Isolation and Characterization of Stigmasterol from Psidium guajava Leaves: A Promising Bioactive Compound with Therapeutic Potential

This study aimed to isolate and characterize bioactive compounds from the leaves of Psidium guajava Linn. The hydroethanolic extract yielded 32% (80 g) from the crude material, which was subjected to column chromatography for fractionation. Structural elucidation of the isolated compound was performed using 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy, including COSY, HSQC, and HMBC experiments. The spectral data confirmed the presence of stigmasterol, characterized by its distinct chemical shifts and long-range correlations between carbon and proton atoms. Stigmasterol was isolated as a white, crystalline solid and identified by its unique physio-chemical properties, such as solubility in organic solvents, a melting point of 163-164°C, and molecular formula C29H48O. This compound is known for its significant biological activities, including antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer effects. By employing advanced techniques like 1D and 2D NMR spectroscopy, the study provides precise structural elucidation of stigmasterol, contributing to natural product research and reinforcing the medicinal potential of guava leaves as a source of pharmacologically active compounds. This adds to the existing knowledge of the plant’s bioactive components and their applications in medicinal chemistry

Quinoline Synthesis: Nanocatalyzed Green Protocols-An Overview.

Heterocyclic compounds are of great interest in our daily lives. They are widely distributed in nature and are synthesized in laboratories. Heterocycles play an important role in the metabolism of all living cells, including vitamins and coenzyme precursors like thiamine and riboflavin. Furthermore, heterocyclic systems are essential building blocks for creating innovative materials with intriguing electrical, mechanical, and biological properties. Also, more than 85% of all biologically active chemical entities comprise a heterocycle. As a result, heterocycle synthesis piqued researchers' curiosity, and in recent decades, chemists have concentrated more on nitrogen-containing cyclic nuclei in structures. Quinoline and its derivatives exhibit several biological functions, including antimicrobial, anticancer, antimalarial, anti-inflammatory, antihypertensive, and antiasthmatic effects. In addition, over a hundred quinoline-based drugs are available to treat a variety of disorders. Because of its biological importance, researchers developed one-pot synthetic methods employing effective acid/base catalysts (Lewis acids, Brønsted acids, and ionic liquids), reagents, and transition-metal-based catalysts. These methods have some downsides, including longer reaction times, harsher reaction conditions, creation of byproducts, costly catalysts, use of hazardous solvents, an unacceptable economic yield, and catalyst recovery. Researchers' focus has switched to creating environmentally friendly and effective methods for the synthesis of quinoline derivatives as a result of these methodologic shortcomings. Because of its special qualities, the use of nanocatalysts or nanocomposites offers an option for the effective synthesis of quinolines. This review focuses on the published research articles on nanocatalysts to synthesize substituted quinoline derivatives. This review covers all contributions until May 2024, focusing on quinoline ring building and mechanistic issues. With the aid of this review, we anticipate that synthetic chemists will be able to develop more effective methods of synthesizing quinolines.

Safety and pharmacokinetic properties of a new formulation of parenteral artesunate in healthy Thai volunteers

BackgroundParenteral artesunate is the first-line therapy for severe malaria. Artesunate, in its current formulation, must be prepared immediately before administration by first dissolving in sodium bicarbonate solution and then diluting in saline. A novel solvent for rapid and stable single step reconstitution of artesunate was recently developed showing improved solubility and stability. This study aimed to compare the safety and pharmacokinetic properties of the currently available and newly developed parenteral formulation of artesunate in healthy Thai volunteers.MethodsThis was an open-label, randomized, 4 periods, 4-treatments, 24-sequence, single-dose, cross-over study in 72 male and female healthy Thai volunteers. Frequent pharmacokinetic samples were collected in all volunteers at each dose occasion. Observed concentration–time profiles were analysed with a non-compartmental approach followed by a bioequivalence evaluation.ResultsBoth intramuscular and intravenous administrations of the new parenteral formulation of artesunate were safe and well-tolerated, with no additional safety signals compared to the currently used formulation. The pharmacokinetic properties of artesunate and its active metabolite, dihydroartemisinin, were well-characterized, and showed rapid conversion of artesunate into dihydroartemisinin. Intramuscular administration of the newly formulated artesunate resulted in almost complete bioavailability of dihydroartemisinin. The pharmacokinetic properties were similar between the old and new formulation.ConclusionsThe new and more easily prepared formulation of artesunate was safe and well-tolerated, with similar pharmacokinetic properties compared to the currently used formulation. Dihydroartemisinin, the active metabolite responsible for the majority of the anti-malarial effect, showed equivalent exposure after both intravenous and intramuscular administration of artesunate, suggesting that both routes of administration should generate comparable therapeutic effects.Trial registration: The study was registered to clinicaltrials.gov (#TCTR20170907002).

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. ObjectiveThus, this 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% Tween80 (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 125mg/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.

Volvariella volvacea (paddy straw mushroom): A mushroom with exceptional medicinal and nutritional properties

Volvariella volvacea, commonly referred to as paddy straw mushroom, is renowned for its remarkable medicinal and nutritional properties. This mushroom, part of the family Pluteaceae, thrives in tropical and subtropical regions and is highly esteemed for its distinctive flavor and substantial health benefits. The fruiting body of V. volvacea is a rich source of bioactive compounds, including antioxidant enzymes, terpenes, polypeptides, sugars, phenolics, and flavonoids. These compounds exhibit an extensive range of therapeutic activities such as anti-tumor, anti-microbial, antioxidant, anti-malarial, anti-cancer, anti-inflammatory, and anti-allergic effects. Nutritionally, V. volvacea is an excellent source of carbohydrates, proteins, fibers, ascorbic acid, and essential minerals. It also boasts a comprehensive profile of amino acids, including valine, arginine, glutamine, serine, aspartic acid, leucine, isoleucine, tyrosine, asparagine, lysine, cystine, proline, glycine, tryptophan, methionine, phenylalanine, threonine, and histidine. This review emphasizes the significant medicinal and nutritional potential of V. volvacea, advocating its inclusion as a functional food to enhance human health and well-being. By highlighting its diverse bioactive compounds and therapeutic benefits, this review aims to foster greater recognition and utilization of paddy straw mushroom in both dietary and medicinal applications.

The effect of resveratrol on the relationship of antioxidant activity and beta-hematin inhibition as an antimalarial action target

Resveratrol is a flavonoid with numerous properties, including antioxidative, anti-inflammatory, anticancer, antimalarial, antidiabetes mellitus, and immunomodulatory effects. In the case of malaria infections, which induce oxidative stress and can lead to various complications, simply administering antimalarials is often insufficient. Therefore, adjuvant therapy, such as antioxidants, is also necessary. Resveratrol exhibits potential as an antimalarial compound and has been reported to demonstrate both in vivo and in vitro antimalarial activity. This study aims to assess the relationship between resveratrol’s antioxidant activity and its inhibition of β-hematin. The antioxidant activity was tested using the 2, 2-diphenyl-1-picrylhydrazyl method, while the β-hematin inhibition assay followed the method outlined by Huy et al. A correlation test was conducted to evaluate the connection between the β-hematin inhibition assay and antioxidant activity. The results demonstrate a strong correlation between antioxidant activity and β-hematin inhibition, with an R = 0.9841 and a P = 0.004. Both of these activities in resveratrol are highly correlated and hold significant potential in the treatment of malaria.

Antimalarial evaluation of selected medicinal plants traditionally used for treatment of fever, by inhibition test of heme polymerization

World Health Organization (WHO) has reported 249 million cases infected by malaria worldwide and 608 thousands deaths in 2022. Investigations for new antimalarial drugs from traditional medicine have proven to be more effective and less expensive. The medicinal plants that have been used for treatment of malaria, generally known as types of fevers in traditional medicine, can be suitable candidates for evaluating antimalarial effects. The aim of the present study was to evaluate the in-vitro mechanism of antimalarial action of selected medicinal plants by inhibition test of heme detoxification (ITHD). The methanol extract and fractions were prepared through maceration of the dry powdered plants. The ITHD method was carried in 96-wells plate and the percentage of heme polymerization inhibition was determined. The cytotoxicity of the effective plants were examined on MDBK cell line by MTT assay. Bioassay guided fractionation was performed exposing to size exclusion column chromatography and liquid-liquid fractionation and was assayed by the ITHD method for the sample with the least IC50 value and lowest cytotoxic effect. The methanol fraction of Viola odorata whole plant showed the most considerable results among the tested plants with IC50 171.8 μg.mL-1 beside the lowest cytotoxic effects. This fraction by the bioassay guided fractionation led to fraction SB2 and this fraction demonstrated the most effective result with lowest IC50 = 14.8 ± 3µg.mL-1 in ITHD assay. Regarding the results of the present study and the traditional use of V. odorata for overcoming fever in Iranian traditional medicine, the final fraction of the plant could be proper candidate for further phytochemical and antimalarial studies.

Nutraceutical and Functional Food Potentials of African Black Elimi (Canarium schweinfurthii): A Review

Study’s Excerpt The potentials of Canarium schweinfurthii in traditional African medicine in treating various ailments due to its rich bioactive composition is extensively explored. 80 publications were synthesized to gather the plant’s diverse nutraceutical and functional properties. The plant has antimalarial, anti-cancer, and antioxidant effects, among others. Full Abstract Medicinal plants have been central to African traditional medicine for centuries, preceding the development of synthetic drugs. Africa is blessed with large medicinal plants that are either under-explored or yet to be studied. This study aimed to find relevant research works on Canarium schweinfurthii with the purpose of identifying a new research niche. One hundred eighteen (118) research journals were collected, and 80 publications were synthesized and used to identify non-repeated experiments on the functional and nutraceutical potentials of Canarium schweinfurthii. The results of the review revealed that different parts of the plant including leaves, stem bark, roots, fruits, seeds, flowers, gum, and resin were traditionally employed in treating a range of ailments, including diabetes, stomach ulcers, malaria, typhoid, leprosy, reproductive disorders, and fever which are attributed to plant’s richness for nutraceutical and functional properties, driven by the presence of bioactive compounds such as antioxidants, alkaloids, saponins, flavonoids, tannins, glycosides, and phenolic compounds. Nutraceutical and functional investigations of the plant have corroborated the antimalarial, anti-cancer, anti-diabetic, analgesic, antioxidant, antimicrobial, anti-bacterial, growth-promoting, nephroprotective, food preservative, anthelmintic, and termiticidal properties of the fruit pulp, fruit bark, stem bark, fruit oil, seed oil of Canarium schweinfurthii. This review recommends the plant for proper establishment of a foundation for the plant’s pharmaceutical application and underscores the need for further research.

Transmission-blocking activities of artesunate, chloroquine, and methylene blue on Plasmodium vivax gametocytes.

Plasmodium vivax is now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low-transmission settings, but they are not well characterized for P. vivax. The transmission-blocking effects of chloroquine, artesunate, and methylene blue on P. vivax gametocytes were assessed. Blood specimens were collected from patients presenting with vivax malaria, incubated with or without the tested drugs, and then fed to mosquitos from a laboratory-adapted colony of Anopheles dirus (a major malaria vector in Southeast Asia). The effects on oocyst and sporozoite development were analyzed under a multi-level Bayesian model accounting for assay variability and the heterogeneity of mosquito Plasmodium infection. Artesunate and methylene blue, but not chloroquine, exhibited potent transmission-blocking effects. Gametocyte exposures to artesunate and methylene blue reduced the mean oocyst count 469-fold (95% CI: 345 to 650) and 1,438-fold (95% CI: 970 to 2,064), respectively. The corresponding estimates for the sporozoite stage were a 148-fold reduction (95% CI: 61 to 470) and a 536-fold reduction (95% CI: 246 to 1,311) in the mean counts, respectively. In contrast, high chloroquine exposures reduced the mean oocyst count only 1.40-fold (95% CI: 1.20 to 1.64) and the mean sporozoite count 1.34-fold (95% CI: 1.12 to 1.66). This suggests that patients with vivax malaria often remain infectious to anopheline mosquitos after treatment with chloroquine. Use of artemisinin combination therapies or immediate initiation of primaquine radical cure should reduce the transmissibility of P. vivax infections.

Secondary Metabolites of Fomitopsis betulina: Chemical Structures, Biological Activity and Application Prospects.

Fomitopsis betulina, as a macrofungus with both medicinal and dietary applications, is renowned for its rich content of bioactive substances. The recent advancements in research have significantly enhanced our understanding of its polysaccharides, cellulose-degrading enzymes, and wide range of secondary metabolites. This paper provides a comprehensive review of the artificial cultivation techniques and the chemical profiling of over 100 secondary metabolites identified in F. betulina, including terpenoids, phenols, and various other classes. These compounds exhibit notable pharmacological activities, such as anti-cancer, anti-inflammatory, antimicrobial, antiviral, and anti-malarial effects. Moreover, this review delves into the genomic analysis of F. betulina, focusing on the prediction and classification of terpene synthases, which play a crucial role in the biosynthesis of these bioactive compounds. This insight is instrumental for potentially facilitating future biochemical studies and pharmaceutical applications. Through this review, we aim to solidify the foundation for future in-depth studies and the development of new drugs derived from this promising natural resource.

Structurally intriguing rearranged bicyclogermacrene-type sesquiterpenoid from Aphania oligophylla

An investigation on the aqueous ethanol extract of the powdered twigs of Aphania oligophylla has afforded a skeletal new sesquiterpenoid aphanoid A (1) and one new aromadendrane-type sesquiterpenoid aphanoid B (2), as well as six known sesquiterpenoids (3–8). Their structures including the absolute configurations were characterized based on spectroscopic data analysis and X-ray crystallography. Compound 1 featuring an unprecedented tricyclo[6.3.1.03,5]dodecane scaffold, is likely rearranged from the bicyclogermacrene-type sesquiterpenoid. Among those compounds, 2 at 10 μL showed moderate antimalarial effect.

Phytochemical Analysis and In Vivo Antimalarial Activities of Ethyl Acetate Fraction of Spilanthes filicaulis on Mice Subjected to Plasmodium berghei.

Background and Objectives: Malaria airs a life-threatening risk in Tropical African countries, stemming from infection by Plasmodium species. This region is richly endowed by nature with a wealth of diverse and largely unexplored plants that hold the potential for managing this protozoan parasite. The currently accessible over-the-counter drugs for disease management often present affordability challenges for the average person, exacerbated by the parasite's increasing resistance to them. This study investigated the phytoconstituents present in the ethyl acetate fraction of Spilanthes filicaulis (EFSF) and explored the antimalarial effects of EFSF on mice infected with Plasmodium berghei. Methods: Standard methods and gas chromatography-mass spectrometry (GC-MS) were used to identify phytoconstituents. Chloroquine phosphate-sensitive P. berghei (NK-65) was intraperitoneally inoculated into Swiss mice. The invivo antimalarial activity of EFSF was assessed at dose levels of 250, 500, and 750 mg/kg, using 4-day suppressive and curative antimalarial models. Parameters evaluated in the inoculated mice included rectal temperature (RT), body weight (BW), packed cell volume (PCV), level of parasitemia, and mean survival time (MST). Results: Steroids, alkaloids, flavonoids, tannins, saponins, terpenoids, and cardiac glycosides were the identified phytochemicals present in EFSF, and GC-MS alongside reveals the presence of 20 bioactive compounds predominantly fatty acids and alcohol esters. Significant prevention of reductions in RT, BW, and PCV was observed in the EFSF-treated groups dose dependently relative to the untreated group. In addition, EFSF-treated groups significantly (p < 0.05) suppressed parasitemia and exhibited chemosuppression of 79.46% and 77.38% in 4-day suppressive, whereas suppression of 59.74% and 58.66% in curative treatment, respectively, at 500 and 750 mg/kg thus consequently extending the MST of infected treated mice compared with the untreated group. Interpretation and Conclusion: Put together, the EFSF exhibited enhanced antimalarial efficacy against mice infected with P. berghei thus affirming that plants still maintain lead way as a potential source of novel antimalarial remedies.

Efficacy of medicinal plants and their derived biomolecules against Plasmodium falciparum

Many apicomplexan pathogens pose significant threats to humans and domestic animals, with the lack of effective drugs and drug resistance representing major challenges in disease management. To address this, the search for new and potent antimalarial drugs is crucial. Plant-based formulations offer a promising alternative for such drug development. Here, we evaluated the in vitro antiplasmodial activity of nine plant extracts, traditionally used to treat fever-like symptoms in Bangladesh. We assessed the antimalarial activity of plant extracts by using the Plasmodium falciparum 3D7 growth inhibition assay, an invasion assay, and a cytotoxicity assay. Of the nine plants studied, ethanolic and methanolic leaf extracts of Ficus hispida, Streblus asper, and Boerhavia repens exhibited high antiplasmodial activity, with IC50 values of 9.31, 4.13, 9.63 μg/ml (ethanolic) and 15.12, 6.63, 7.58 μg/ml (methanolic), respectively, and minimal toxicity (cell viability >80%). Clerodendrum viscosum displayed antiplasmodial effects with IC50 values of 28.90 μg/ml (ethanolic) and 30.57 μg/ml (methanolic). Adhatoda vasica, Mussaenda corymbosa, and Amaranthus spinosus ethanolic extracts showed antimalarial effects with IC50 values of 61.78 μg/ml, 66.31 μg/ml, and 64.14 μg/ml, respectively. However, methanolic extracts of A. vasica and A. spinosus had IC50 values >100 μg/ml. The ethanolic and methanolic extracts of A. vasica, A. spinosus, F. hispida, S. asper, and B. repens significantly reduced parasitemia by inhibiting invasion into erythrocytes. This study highlights the robust antimalarial activity and low cytotoxicity of leaf extracts of F. hispida, S. asper, and B. repens, indicating the presence of antimalarial compounds that warrant further investigation.

Relationships of Prodiginins Mechanisms and Molecular Structures to their Antiproliferative Effects.

The Prodiginins (PGs) natural pigments are secondary metabolites produced by a broad spectrum of gram-negative and gram-positive bacteria, notably by species within the Serratia and Streptomyces genera. These compounds exhibit diverse and potent biological activities, including anticancer, immunosuppressive, antimicrobial, antimalarial, and antiviral effects. Structurally, PGs share a common tripyrrolic core but possess variable side chains and undergo cyclization, resulting in structural diversity. Studies have investigated their antiproliferative effects on various cancer cell lines, with some PGs advancing to clinical trials for cancer treatment. This review aims to illuminate the molecular mechanisms underlying PG-induced apoptosis in cancer cells and explore the structure-activity relationships pertinent to their anticancer properties. Such insights may serve as a foundation for further research in anticancer drug development, potentially leading to the creation of novel, targeted therapies based on PGs or their derivatives.

Antimalarial Drugs at the Intersection of SARS-CoV-2 and Rheumatic Diseases: What Are the Potential Opportunities?

Background and Objectives: The coronavirus disease of 2019 (COVID-19) pandemic has posed a serious threat to humanity and is considered a global health emergency. Antimalarial drugs (ADs) have been used in the treatment of immuno-inflammatory arthritis (IIA) and coronavirus infection (COVID-19). The aim of this review is to analyze the current knowledge about the immunomodulatory and antiviral mechanisms of action, characteristics of use, and side effects of antimalarial drugs. Material and Methods: A literature search was carried out using PubMed, MEDLINE, SCOPUS, and Google Scholar databases. The inclusion criteria were the results of randomized and cohort studies, meta-analyses, systematic reviews, and original full-text manuscripts in the English language containing statistically confirmed conclusions. The exclusion criteria were summary reports, newspaper articles, and personal messages. Qualitative methods were used for theoretical knowledge on antimalarial drug usage in AIRDs and SARS-CoV-2 such as a summarization of the literature and a comparison of the treatment methods. Results: The ADs were considered a "candidate" for the therapy of a new coronavirus infection due to mechanisms of antiviral activity, such as interactions with endocytic pathways, the prevention of glycosylation of the ACE2 receptors, blocking sialic acid receptors, and reducing the manifestations of cytokine storms. The majority of clinical trials suggest no role of antimalarial drugs in COVID-19 treatment or prevention. These circumstances do not allow for their use in the treatment and prevention of COVID-19. Conclusions: The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for COVID-19. Furthermore, the need for high doses in the treatment of viral infections increases the likelihood of gastrointestinal side effects, the prolongation of QT, and retinopathy. Large randomized clinical trials (RCTs) have refuted the fact that there is a positive effect on the course and results of COVID-19.

In vitro, in vivo and in silico antiplasmodial profiling of the aqueous extract of Hibiscus asper HOOK F. Leaf (Malvaceae)

Ethnopharmacological relevancePlasmodium resistance to antimalarial drugs raises the urgent need to seek for alternative treatments. Aqueous extract of Hibiscus asper leaves is currently used in malaria management but remains less documented.Aim of the study: The study aims to evaluate antimalarial effects of the aqueous extract of Hibiscus asper. UHPLC/MS, was used to identify some likely compounds present in the plant that were thereafter docked to some malaria parasite proteins. Study designIn vitro anti-plasmodium and antioxidant, UHPLC/Ms analysis, in vivo antimalarial of the plant extract, and in silico molecular docking prediction of some identified compounds were performed to investigate the pharmacological effects of H. asper. Material and methodsThe in vitro antiplasmodial activity of the extract was carried out on Plasmodium falciparum strains using SYBR-green dye; then, the curative antimalarial activity was conducted on Plasmodium berghei NK65-infected male Wistar rats. The UHPLC/MS analysis was used to identify plant compounds, followed by interactions (docking affinity) between some compounds and parasitic enzymes such as P. falciparum purine nucleoside phosphorylase (2BSX) and 6-phosphogluconate dehydrogenase (6FQY) to explore potential mechanisms of action at the molecular level. ResultsNo hemolysis effect of the extract was observed at concentrations up to 100 mg/mL. In vitro test of the aqueous leaves extract of H. asper showed inhibitory activity against P. falciparum Dd2 and 3D7 strains with IC50 values of 19.75 and 21.97 μg/mL, respectively. The curative antimalarial test of the H. asper extract in infected rats exhibited significant inhibition of the parasite growth (p < 0.001) with inhibition percentage of 95.11%, 97.68% and 95.59% at all the doses (50, 100 and 200 mg/kg) respectively. The extract corrected major physiological alterations such as liver and kidney impairments, oxidative stress and architectural disorganization in liver, spleen and kidneys tissues. The UHPLC/MS analysis identified 7 compounds, namely chlorogenic acid, azulene, quercetin, rhodine, 1-ethyl-2,4-dimethyl benzene and phthalan. Out of seven compounds identified in the extract quercetin and phthalan showed higher in silico inhibitory activity against P. falciparum purine nucleoside phosphorylase and Plasmodium falciparum 6-phosphosgluconate dehydrogenase parasite enzymes. ConclusionThese findings indicate that H. asper could be a promising complementary medicine to manage malaria. Meanwhile, the affinity of annoted compounds with these enzymes should be further confirmed.

The Structure-Antiproliferative Activity Relationship of Pyridine Derivatives.

Pyridine, a compound with a heterocyclic structure, is a key player in medicinal chemistry and drug design. It is widely used as a framework for the design of biologically active molecules and is the second most common heterocycle in FDA-approved drugs. Pyridine is known for its diverse biological activity, including antituberculosis, antitumor, anticoagulant, antiviral, antimalarial, antileishmania, anti-inflammatory, anti-Alzheimer's, antitrypanosomal, antimalarial, vasodilatory, antioxidant, antimicrobial, and antiproliferative effects. This review, spanning from 2022 to 2012, involved the meticulous identification of pyridine derivatives with antiproliferative activity, as indicated by their minimum inhibitory concentration values (IC50) against various cancerous cell lines. The aim was to determine the most favorable structural characteristics for their antiproliferative activity. Using computer programs, we constructed and calculated the molecular descriptors and analyzed the electrostatic potential maps of the selected pyridine derivatives. The study found that the presence and positions of the -OMe, -OH, -C=O, and NH2 groups in the pyridine derivatives enhanced their antiproliferative activity over the cancerous cellular lines studied. Conversely, pyridine derivatives with halogen atoms or bulky groups in their structures exhibited lower antiproliferative activity.

Indoloquinoline Alkaloids as Antimalarials: Advances, Challenges, and Opportunities.

Malaria infections affect almost half of the world's population, with over 200 million cases reported annually. Cryptolepis sanguinolenta, a plant native to West Africa, has long been used across various regions of Africa for malaria treatment. Chemical analysis has revealed that the plant is abundant in indoloquinolines, which have been shown to possess antimalarial properties. Cryptolepine, neocryptolepine, and isocryptolepine are well-studied indoloquinoline alkaloids known for their potent antimalarial activity. However, their structural rigidity and associated cellular toxicity are major drawbacks for preclinical development. This review focuses on the potential of indoloquinoline alkaloids (cryptolepine, neocryptolepine, and isocryptolepine) as scaffolds in drug discovery. The article delves into their antimalarial effects in vitro and in vivo, as well as their proposed mechanisms of action and structure-activity relationship studies. Several studies aim to improve these leads by reducing cytotoxicity while preserving or enhancing antimalarial activity and gaining insights into their mechanisms of action. These investigations highlight the potential of indoloquinolines as a scaffold for developing new antimalarial drugs.