Antiplasmodial Properties Research Articles

Isolation of Antiplasmodial Oxazoles and Isoflavonoids from the Roots of Oxytropis trichophysa and Total Synthesis of Oxazole-type Alkaloids.

A chemical examination of a root extract of Oxytropis trichophysa led to the isolation and identification of 23 compounds, including oxazole-type alkaloids and isoflavonoid derivatives. Notably, three oxazole-type alkaloids (1, 2, and 3) and two isoflavonoid derivatives (7 and 10) were obtained from a natural source for the first time. In addition, O. trichophysa derived 2,5-diphenyloxazoles and their derivatives were synthesized. Despite their potential activity, the antiplasmodial activities of naturally occurring 2,5-diphenyloxazoles and certain isoflavonoids remain unexplored. Therefore, the antiplasmodial activities of both the naturally occurring and synthesized compounds were evaluated against Plasmodium falciparum strain 3D7. Among the tested compounds, three naturally occurring oxazole-type alkaloids (1, 5, and 6), one synthesized alkaloid (34), and two isoflavonoid derivatives (13 and 15) demonstrated significant inhibitory effects, with half-maximal inhibitory concentration (IC50) values ranging from 3.1 to 6.2 μM and selective indices between 0.9 and 18.8. Compound 1 showed the most potent inhibitory activity, with an IC50 of 3.1 μM, while its cytotoxic concentration 50% value against human foreskin fibroblasts was found to be 8.5 μM. The oxazole-type alkaloids and isoflavonoids isolated from this plant provide valuable insights into its chemical composition and may help elucidate the antiplasmodial properties of O. trichophysa.

Bioactive Sulfonamides Derived from Amino Acids: Their Synthesis and Pharmacological Activities.

Currently, the synthesis of bioactive sulfonamides using amino acid as a starting reagent has become an area of research interest in organic chemistry. Over the years, an amine-sulfonyl chloride reaction has been adopted as a common step in traditional sulfonamide synthetic methods. However, recent developments have shown amino acids to be better precursors than amines in the synthesis of sulfonamides. Although amines and amino acids have some structural similarities, using amino acids rather than amines in the synthesis of sulfonamides minimizes several drawbacks. Comparatively, amino acids are preferred to amines as starting reagents in sulfonamide synthesis due to their biological relevance, chirality, stereochemistry, diversity of side chains, orthogonality in functional group manipulation, the potential for peptide and protein synthesis, mild reaction conditions, alignment with green chemistry principles, diverse synthetic applications, easy availability, and economic viability. Amino acids, having the aforementioned properties, offer a versatile platform for the synthesis of sulfonamides with tailored structures. The reaction mechanism of the synthesis of amino acid-derived sulfonamides involves a nucleophilic attack by the amino group on the activated sulfonyl species to produce a sulfonamide functional group. Amino acid-based sulfonamides have numerous pharmacological activities, including antibacterial, antiviral, anticancer, antioxidant, anti-inflammatory, anti-plasmodial, antimalarial, anti-trypanosomal, and insect growth regulatory properties. This review discusses several synthetic processes, emphasizing established ways, cutting- edge techniques, and novel approaches that emphasize the significance of amino acids in the synthesis of sulfonamides. The structure-activity relationship of amino acid-derived sulfonamides and their pharmacological activities are also highlighted.

Pharmacological Effects of Biosynthesis Silver Nanoparticles Utilizing Calotropis procera Leaf Extracts on Plasmodium berghei-Infected Liver in Experiment Mice.

Malaria caused by Plasmodium spp. is the most hazardous disease in the world. It is regarded as a life-threatening hematological disorder caused by parasites transferred to humans by the bite of Anopheles mosquitoes. Calotropis procera leaf extract combined with biosynthesized silver nanoparticles (CPLEAgNPs) to evaluate its antiplasmodium and hepatoprotective effects against P. berghei-induced infection in experimental mice. The animal groups were divided into four groups: the first non-infected group was orally administered distilled water daily 7 days. The second group received an oral dose of 50 mg/kg of CPLE AgNPs. The third group received intraperitoneal injections of 105 P. berghei. The fourth group received of 105 P. berghei with 50 mg/kg CPLE AgNPs. All mice were anesthetized with CO2 and dissected for sample collection. This study of C. procera leaves showed that they contain chemically active substances, as shown by the amounts of phenols, flavonoids, and tannins. The antioxidant activity of the samples was assessed using 1.1-diphenyl-2-picrylhydrazyl (DPPH) and 2.2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assays. Treatment of infected mice with CPLE AgNPs for 7 days resulted in a significant decrease in parasitemia and a reduction in histopathological alterations in the liver. Furthermore, CPLE AgNPs mitigated oxidative damage caused by P. berghei infection in the liver. In addition, after receiving the medication, the liver levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase decreased. In addition, CPLE AgNPs regulated the expression of liver cytokines, including IL-1β, and I-10. Based on these findings, the study proved that CPLE AgNPs have hepatoprotective and antiplasmodial properties.

Bioactive metabolites of Brazilian Red Propolis: Cytotoxic, antimalarial, and antimicrobial properties.

Brazilian Red Propolis (BRP) is a natural product known for its rich chemical composition and therapeutic potential. This study investigates the phytochemical profile and evaluates the cytotoxic, antiplasmodial, and antimicrobial properties of red propolis extract and its isolated compounds vestitol (1), neovestitol (2), medicarpin (3), 7-O-methylvestitol (4), and oblongifolin B (5). The extract showed selective cytotoxicity against cancer cell lines (IC50: 16-39 μg/mL). Compound 3 exhibited a promising cytotoxicity against SK-OV-3 with and IC50 of 6.65 μM. BRP had moderate antimicrobial effects; however, 3 was effective against Cryptococcus neoformans (IC50: 19.29 μM), while 5 was active against Pseudomonas aeruginosa (IC50: 15.77 μM). BRP exhibited antiplasmodial activity against Plasmodium falciparum strains D6 and W2 (IC50: 13.8 μg/mL and 5.7 μg/mL); also, 4 and 5 had IC50 concentrations ranging from: 2.99-6.96 μM). Molecular docking for P. falciparum lactate dehydrogenase (PfLDH), suggest that compound 4 has significant interactions with critical residues in the PfLDH active site, such as TYR85, THR97, and ASP53, and falls within optimal ranges for oral bioavailability. These findings highlight the significant bioactive potential of BRP and its compounds, suggesting their potential as therapeutic agents in vitro and in-silico. Further studies are recommended to explore their mechanisms of action and therapeutic applications.

Antiplasmodial potential of compounds isolated from Ziziphus mucronata and their binding to Plasmodium falciparum HGXPRT using biophysical and molecular docking studies.

The increasing resistance of Plasmodium parasites to currently available antiplasmodial therapies poses a significant challenge in treating malaria. Since ancient times, plants have served as a primary source of novel pharmacologically active compounds for drug development. Therefore, this study aimed to explore the antiplasmodial properties of pentacyclic triterpenes isolated from Ziziphus mucronata bark, with an emphasis on their mechanism of action. Dichloromethane and ethyl acetate extracts of the stem bark were subjected to silica gel column chromatography, which led to the isolation of three known triterpenoids: betulinic acid, methyl betulinate, and lupeol. The compounds were then evaluated for antiplasmodial activity against Plasmodium falciparum NF54 strains using the Plasmodium lactate dehydrogenase (pLDH) assay. In silico evaluation of the isolated compounds was conducted through molecular docking and further validated with in vitro experiments against a purified protein target, Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT). Betulinic acid, methyl betulinate, and lupeol exhibited potent antiplasmodial activities with IC50 values of 20, 10.11, and 7.56µg/mL, respectively. Lupeol exhibited the highest binding energy of - 7.6kcal/mol. Differential scanning fluorimetry revealed that lupeol decreases the Tm of PfHGXPRT, thus decreasing the protein's thermal stability. At high concentrations, lupeol also increased protein absorbance, indicating the detection of hydrophobic amino acids and protein unfolding. This study proves that Z. mucronata could serve as a reservoir of effective agents for treating malaria, while also scientifically validating its use in traditional medicine. However, further experimental studies are required to substantiate its relevant therapeutic effects.

Exploring the Antimalarial Efficacy of Globimetula oreophila Leaf Fractions in Plasmodium berghei-Infected Mice: In Vivo Approach

The development of parasite resistance to first-line antimalarial medicines, especially the Artemisinin-based combination therapies (ACTs), has made the research and development of novel antimalarial medications vital. Globimetula oreophila, a plant used in traditional medicine to treat malaria, is a natural product that may provide new antimalarial drugs with fewer side effects, greater efficacy and lower risk of resistance than synthetic drugs. This study aims to evaluate the antiplasmodial properties of G. oreophila's fractions. The plant leaves were air-dried and reduced in size using a pestle and mortar. The pulverized plant was macerated in 70% ethanol and fractionated with solvent in increasing polarity of n-hexane, chloroform, ethyl acetate, and n-butanol to produce the various fractions. The antiplasmodial activity of the n-hexane, chloroform, ethyl acetate, and n-butanol fractions of G. oreophila leaf extract was assessed using an in vivo method in Plasmodium berghei-infected mice via prophylactic, suppressive, and curative test. The fractions' median lethal dose (LD50) was estimated to be greater than 5000 mg/kg in mice. The median effective dose (ED50) of the fractions at doses of 125, 250, and 500 mg/kg produced a significant (p<0.001) decrease in the level of parasitemia. The ethyl acetate fraction had the best antiplasmodium activity compared to other plant fractions. The fractions of G. oreophila showed significant in vivo antiplasmodial activity, which upholds the earlier in vivo findings for the crude extract and its folkloric use. Further study should be carried out to isolate active secondary metabolites responsible for this observed antimalarial activity in all four investigated fractions.

Unveiling the 4-aminoquinoline derivatives as potent agents against pancreatic ductal adenocarcinoma (PDAC) cell lines

Common antimalarials such as artemisinins, chloroquine and their derivatives also possess potent anti-inflamantory, antiviral and anticancer properties. In the search for new therapeutics to combat difficult-to-treat pancreatic carcinomas, we unveiled that 4-aminoquinoline derivatives, with significant antiplasmodial properties and a great safety profile in vivo, have remarkable anticancer activity against pancreatic ductal adenocarcinoma (PDAC) and considerable efficacy in the xenograft model in vivo. The aim of the present study was to further investigate anticancer properties of these compounds in a drug-repurposing manner. The compounds showed profound cytotoxic effects at nanomolar to low micromolar concentration in 2D cultured cells (in vitro) and in the zebrafish PDAC xenograft model (in vivo). A deeper insight into their mechanisms of cytotoxic action showed these compounds induce apoptosis while increasing reactive oxygen species levels along with autophagy inhibition. Additional investigation of the autophagy modulation proved that tested quinoline derivatives cause P62 and LC3-II accumulation in PDAC cells alongside lysosomal alkalinization. Further, in vivo toxicity studies in the zebrafish model showed low toxicity without developmental side effects of the investigated 4-aminoquinolines, while the applied compounds effectively inhibited tumor growth and prevented the metastasis of xenografted pancreatic cells. Taken together, these results highlight the 4-aminoquinolines as privileged structures that ought to be investigated further for potential application in pancreatic carcinoma treatment.

Exploring the Antimalarial Potential of Entandrophragma Utile and Melochia Umbellata Extracts.

Resistance remains the fundamental problem with antiplasmodial treatments. The study investigated the antiplasmodial, cytotoxic, and antioxidant properties of two Cameroonian medicinal plants, Entandrophragma utile and Melochia umbellata. Antimalarial activity against Plasmodium falciparum strains 3D7 and Dd2 was assessed using the SYBR Green I assay. Cytotoxicity was assessed against Raw and Vero cells using the resazurin assay, and against red blood cells using a hemoglobin release quantification assay. Antioxidant potential was determined using DPPH (2, 2-diphenyl-1-picrylhydrazine), ABTS (2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and FRAP (ferric-reducing antioxidant power) assays. The most bioactive extract was further analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) to determine its phytochemical composition. Extracts from E. utile exhibited moderate anti-malarial activity against Plasmodium falciparum (IC50 =32.81-100 μg/mL), while M. umbellata leaf extract (MULAE) showed strong activity (IC50 =11.62 and 11.91 μg/mL). All extracts demonstrated antioxidant activity (9.22 to 135.8 μg/mL), were selective for Raw and Vero cells, and were not toxic to red blood cells. UHPLC-MS analysis annotated potential pyrimidones, phenolic compounds, and terpenoids in MULAE. MULAE exhibited better antiplasmodial activity, suggesting the presence of unique bioactive compounds. Further research, including in vivo investigations, is needed to develop safe and effective antiplasmodial therapies.

The Diverse Activities and Mechanisms of the Acylphloroglucinol Antibiotic Rhodomyrtone: Antibacterial Activity and Beyond.

Background/Objectives: The rose myrtle Rhodomyrtus tomentosa is a medicinal plant used in traditional Asian medicine. The active compound in R. tomentosa leaf extracts is rhodomyrtone, a chiral acylphloroglucinol. Rhodomyrtone exhibits an impressive breadth of activities, including antibacterial, antiviral, antiplasmodial, immunomodulatory, and anticancer properties. Its antibacterial properties have been extensively studied. Methods: We performed a comprehensive literature review on rhodomyrtone and summarized the current knowledge about this promising acylphloroglucinol antibiotic and its diverse functions in this review. Results: Rhodomyrtone shows nano to micromolar activities against a broad range of Gram-positive pathogens, including multidrug-resistant clinical isolates, and possesses a unique mechanism of action. It increases membrane fluidity and creates hyperfluid domains that attract membrane proteins prior to forming large membrane vesicles, effectively acting as a membrane protein trap. This mechanism affects a multitude of cellular processes, including cell division and cell wall synthesis. Additionally, rhodomyrtone reduces the expression of inflammatory cytokines, such as TNF-α, IL-17A, IL1β, and IL8. Generally showing low toxicity against mammalian cells, rhodomyrtone does inhibit the proliferation of cancer cell lines, such as epidermal carcinoma cells. The primary mechanism behind this activity appears to be the downregulation of adhesion kinases and growth factors. Furthermore, rhodomyrtone has shown antioxidant activity and displays cognitive effects, such as decreasing depressive symptoms in mice. Conclusions: Rhodomyrtone shows great promise as therapeutic agent, mostly for antibacterial but also for diverse other applications. Yet, bottlenecks such as resistance development and a better understanding of mammalian cell toxictiy demand careful assessment.

In Vivo and In Silico Evaluation of the Anti-plasmodial Properties of the Ethanolic Fraction of Chromolaena odorata

In Vivo and In Silico Evaluation of the Anti-plasmodial Properties of the Ethanolic Fraction of Chromolaena odorata

Antioxidant and Antiplasmodial Potentials of Methanol Bark Extract of <i>Entada africana </i>Via <i>in Vitro</i> Approaches

<i>Plasmodium </i>parasites, which cause malaria, continue to pose a serious threat to global health, necessitating the continuous search for novel antimalarial agents. Oxidative stress has also been linked to the pathophysiology of malaria. <i>Entada africana</i> is a plant known for its ethnomedicinal uses in treating various ailments associated with inflammation including malaria. This study aimed at evaluating the antiplasmodial and antioxidant potentials of methanol bark extract from <i>Entada africana </i>(MBEEA). <i>In vitro </i>approaches were adopted for the study.<i> Plasmodium falciparum-</i>infected erythrocyte samples were cultured in Roswell Park Memorial Institute (RPMI) 1640 media under anaerobic conditions for 72 hours. Eighteen test tubes were labeled and grouped into three replicates per group. Group I (untreated), Group II, and III were treated with chloroquine (CQ) and artemether (AR) at a concentration of 5 mg/dL. Group IV, V, and VI were treated with the extract at respective concentrations of 5 mg/dL, 10 mg/dL, and 20 mg/dL for 72 hours. The parasitemia count and the percentage parasitemia inhibition were determined by microscopic examination of Giemsa-stained smears. The antioxidant potential of the extract was assessed using <i>in vitro</i> assays, including superoxide radical scavenging activity (SRSA), hydroxyl radical scavenging activity (HRSA), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP). Microscopic examination of the treated samples revealed varying degrees of parasitemia inhibition. Group II and III treated with CQ and AR demonstrated a considerable reduction in parasitemia count with percentage inhibition of 100% and 83% respectively. The <i>E. africana</i> extract showed a concentration-dependent effect on parasitemia count. At 5 mg/dL, the extract exhibited 50% parasitemia inhibition, which increased to 100% at 10 mg/dL, and 20 mg/dL respectively. The MBEEA demonstrated significant <i>in vitro </i>antioxidant activities by scavenging DPPH, SRSA, and hydroxyl radical compared to the standard antioxidant (ascorbic acid). MBEEA thus exhibit potent antioxidant and antiplasmodial properties. This plant is therefore offers to be a promising medicinal plant in the treatment of malaria, hence it is recommended as potent antiplasmodial plant usable for treating malaria.

In vitro antiplasmodial and anticancer analyses of endophytic fungal extracts isolated from selected Nigerian medicinal plants

Ethnomedicinal plants are thought to have better prospects of harboring endophytes that produce natural products with pharmacological activities. This study aimed to investigate the antiplasmodial and anticancer properties of secondary metabolites of endophytic fungi from three medicinal plants. The endophytic fungi included Lasiodiplodia theobromae isolated from Cola acuminata, Curvularia lunata Bv4 isolated from Bambusa vulgaris, and Curvularia lunata Eg7 isolated from Elaeis guineensis. The identification of the fungi was based on the internal transcribed spacer (ITS-rDNA) sequence. The fungi were subjected to solid-state fermentation and the secondary metabolites were extracted with ethyl acetate. In vitro antiplasmodial screening of extracts was performed using the SYBR green I-based fluorescence assay on the chloroquine-resistant Plasmodium falciparum strain DD2. The cytotoxicity of the extracts on human red blood cells and Jurkat (leukemia) cells was assessed using the tetrazolium-based colorimetric MTT assay. Gas chromatography-mass spectrometry (GC–MS) analysis was used to identify the constituents of the fungal extracts. The extract of L. theobromae showed the best antiplasmodial activity against chloroquine-resistant P. falciparum (IC50 = 5.4 µg/mL) and was not harmful to erythrocytes (CC50 > 100 µg/mL). All three fungal extracts showed a weak cytotoxic effect against Jukart cell lines (CC50 > 100 µg/mL). GC–MS analysis of the three endophytic fungal extracts revealed the presence of forty major bioactive compounds, including: oxalic acid, isobutyl nonyl ester, 2,4-di-tert-butylphenol, and hexadecanoic acid, among others. The endophytic fungi from the medicinal plants in this study were promising sources of bioactive compounds that could be further evaluated as novel drugs for the treatment of malaria caused by P. falciparum-resistant strains.

Therapeutic potential of Garcinia kola against experimental toxoplasmosis in rats.

Cerebral toxoplasmosis, the most common opportunistic infection in immunocompromised individuals, is increasingly reported in immunocompetent individuals due to mutant strains of Toxoplasma gondii, which, furthermore, are reported to be resistant to available treatments. We assessed the therapeutic potential of Garcinia kola, a medicinal plant reported to have antiplasmodial and neuroprotective properties, against experimental toxoplasmosis in rats. Severe toxoplasmosis was induced in male Wistar rats (156.7 ± 4.1 g) by injecting them with 10 million tachyzoites in suspension in 500 µl of saline (intraperitoneal), and exclusive feeding with a low-protein diet [7% protein (weight by weight)]. Then, animals were treated with hexane, dichloromethane, and ethyl acetate fractions of Garcinia kola. Footprints were analysed and open-field and elevated plus maze ethological tests were performed when symptoms of severe disease were observed in the infected controls. After sacrifice, blood samples were processed for Giemsa staining, organs were processed for haematoxylin and eosin staining, and brains were processed for Nissl staining and cell counting. Compared with non-infected animals, the infected control animals had significantly lower body weights (30.27%↓, P = 0.001), higher body temperatures (P = 0.033) during the sacrifice, together with signs of cognitive impairment and neurologic deficits such as lower open-field arena centre entries (P < 0.001), elevated plus maze open-arm time (P = 0.029) and decreased stride lengths and step widths (P < 0.001), as well as neuronal loss in various brain areas. The ethyl acetate fraction of Garcinia kola prevented or mitigated most of these signs. Our data suggest that the ethyl acetate fraction of Garcinia kola has therapeutic potential against cerebral toxoplasmosis.

Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico.

Plakortinic acids C (1) and D (2), an unseparable pair of endoperoxide polyketides isolated and purified from the symbiotic association of Caribbean Sea sponges Plakortis symbiotica-Xestospongia deweerdtae, underwent in vitro evaluation for antiplasmodial activity against the malaria parasite Plasmodium berghei using a drug luminescence assay. Initial screening at 10 µM revealed 50% in vitro parasite growth inhibition. The title compounds displayed antiplasmodial activity with an EC50 of 5.3 µM toward P. berghei parasites. The lytic activity against erythrocytes was assessed through an erythrocyte cell lysis assay, which showed non-lytic activity at lower concentrations ranging from 1.95 to 3.91 µM. The antiplasmodial activity and the absence of hemolytic activity support the potential of plakortinic acids C (1) and D (2) as promising lead compounds. Moreover, drug-likeness (ADMET) properties assessed through the pkCSM server predicted high intestinal absorption, hepatic metabolism, and volume of distribution, indicating favorable pharmacokinetic profiles for oral administration. These findings suggest the potential suitability of these metabolites for further investigations of antiplasmodial activity in multiple parasitic stages in the mosquito and Plasmodium falciparum. Notably, this study represents the first report of a marine natural product exhibiting the unique 7,8-dioxatricyclo[4.2.2.02,5]dec-9-ene motif being evaluated against malaria.

Evaluation of the antiplasmodial and anti-Toxoplasma activities of several Indonesian medicinal plant extracts

Ethnopharmacological relevanceMalaria, caused by Plasmodium parasites, remains a significant global health challenge, particularly in tropical and subtropical regions. At the same time, the prevalence of toxoplasmosis has been reported to be 30% worldwide. Traditional medicines have long played a vital role in discovering and developing novel drugs, and this approach is essential in the face of increasing resistance to current antimalarial and anti-Toxoplasma drugs. In Indonesian traditional medicine, various plants are used for their therapeutic properties. This study focuses on eleven medicinal plants from which nineteen extracts were obtained and screened for their potential medicinal benefits against malaria and toxoplasmosis. Aims of the studyThe aim of this study was to evaluate the efficacy of extracts from Indonesian medicinal plants to inhibit Plasmodium falciparum, a parasite responsible for malaria, and Toxoplasma gondii, an opportunistic parasite responsible for toxoplasmosis. MethodsNineteen extracts from eleven plants were subjected to in vitro screening against P. falciparum 3D7 (a chloroquine-sensitive strain) and the T. gondii RH strain. In vitro treatments were conducted on P. falciparum 3D7 and K1 (multidrug-resistant strains) using the potent extracts, and in vivo assessments were carried out with mice infected with P. yoelii 17XNL. LCMS analysis was also conducted to identify the main components of the most effective extract. ResultsSeven extracts showed significant antiplasmodial activity (>80% inhibition) at a concentration of 100 μg/ml. These extracts were obtained from Dysoxylum parasiticum (Osbeck) Kosterm., Elaeocarpus glaber (Bl.) Bijdr., Eleutherine americana Merr., Kleinhovia hospita L., Peronema canescens Jack, and Plectranthus scutellarioides (L.) R.Br. Notably, the D. parasiticum ethyl acetate extract exhibited high selectivity and efficacy both in vitro and in vivo. Herein, the key active compounds oleamide and erucamide were identified, which had IC50 values (P. falciparum 3D7/K1) of 17.49/23.63 μM and 32.49/51.59 μM, respectively. ConclusionsThe results of this study highlight the antimalarial potential of plant extracts collected from Indonesia. Particularly, extracts from D. parasiticum EtOH and EtOAc stood out for their low toxicity and strong antiplasmodial properties, with the EtOAc extract emerging as a notably promising antimalarial candidate. Key compounds identified within this extract demonstrate the complexity of extracts' action against malaria, potentially targeting both the parasite and the host. This suggests a promising approach for developing new antimalarial strategies that tackle the multifaceted challenges of drug resistance and disease management. Future investigations are necessary to unlock the full therapeutic potential of these extracts.

Antimicrobial and Antiplasmodial Activities of Endophytic Fungi Associated with Psidium guajava

Infections due to antimicrobial-resistant microorganisms have become widespread in recent years. Thus, searching for novel antimicrobial agents to combat such pathogens has become crucial. The current study aimed to evaluate the antimicrobial, antiplasmodial, and immunomodulatory activities of the extracts of endophytic fungi isolated from Psidium guajava. Isolation, identification, fermentation, and extraction of the secondary metabolites of the fungal endophytes were carried out following standard procedures. The extracts were subjected to High-Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis to detect their bioactive components. The Antimicrobial activity and Minimum Inhibitory Concentration of the fungal extracts were evaluated against pure cultures of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia using Agar well diffusion and Agar dilution method respectively. The acute toxicity study (LD50) was carried out using Lorke’s method. The extracts were tested in vivo in mice for antiplasmodial activity against Plasmodium berghei and in vitro against Plasmodium falciparum using Peter and Reyley's curative test method and WHO standardized micro-test system with modification respectively. The immunomodulatory activity of the extracts was evaluated by cyclophosphamide-induced myelosuppression (hematological parameters). Active extracts were further subjected to Delayed-Type Hypersensitivity Response (DTHR) and Haemagglutination Inhibition Assay using Sheep Red Blood Cells as antigens. The result showed Alternaria sp. (PGL1, PGL2, PGL3), from P. guajava. The HPLC-DAD analysis revealed the presence of bioactive compounds previously reported to have antimicrobial, antiplasmodial, and immunomodulatory properties. The fungal extracts exhibited varying degrees of antimicrobial activity. The LD50 of the fungi extracts was&gt;5000 mg/kg in mice. The extracts at 100 and 200 mg/kg body weight in mice showed varying degrees of antiplasmodial activity. Growth of P. berghei was significantly (p&lt;0.001) inhibited, curative effect ranges from 59.09 – 100%. Schizont maturation of P. falciparum isolates was inhibited and the highest level of inhibition was observed at 1 mg/ml (p&lt;0.05). The fungal extracts reversed the effect of cyclophosphamide-induced reduction in total white blood cell counts and % neutrophil. This study showed that the tested plant harbors species of endophytic fungi that contain numerous secondary metabolites. The endophytic fungi showed prophylactic, immunostimulatory, and antiplasmodial activities, which can be exploited to develop antimicrobial, antiplasmodial, and immunomodulatory agents.

Antiplasmodial potential of phytochemicals from Citrus aurantifolia peels: a comprehensive in vitro and in silico study

Phytochemical investigation of Key lime (Citrus aurantifolia L., F. Rutaceae) peels afforded six metabolites, known as methyl isolimonate acetate (1), limonin (2), luteolin (3), 3ˋ-hydroxygenkwanin (4), myricetin (5), and europetin (6). The structures of the isolated compounds were assigned by 1D NMR. In the case of limonin (2), further 1- and 2D NMR experiments were done to further confirm the structure of this most active metabolite. The antiplasmodial properties of the obtained compounds against the pathogenic NF54 strain of Plasmodium falciparum were assessed in vitro. According to antiplasmodial screening, only limonin (2), luteolin (3), and myricetin (5) were effective (IC50 values of 0.2, 3.4, and 5.9 µM, respectively). We explored the antiplasmodial potential of phytochemicals from C. aurantifolia peels using a stepwise in silico-based analysis. We first identified the unique proteins of P. falciparum that have no homolog in the human proteome, and then performed inverse docking, ΔGBinding calculation, and molecular dynamics simulation to predict the binding affinity and stability of the isolated compounds with these proteins. We found that limonin (2), luteolin (3), and myricetin (5) could interact with 20S a proteasome, choline kinase, and phosphocholine cytidylyltransferase, respectively, which are important enzymes for the survival and growth of the parasite. According to our findings, phytochemicals from C. aurantifolia peels can be considered as potential leads for the development of new safe and effective antiplasmodial agents.

Investigation of the anti-salmonellal and antiplasmodial properties of leaf extracts of Rourea coccinea Beninese medicinal plant

Rourea coccinea, also called Byrsocarpus coccineus is a medicinal plant widely used in primary health care in West Africa and in this case in Benin. In the present study, the hydroethanolic extract of these leaves was investigated for its anti-salmonella and antiplasmodial properties. The evaluation of anti-salmonella activity was carried out by the micro dilution method associated with resazurine while that of antiplasmodial activity by method described by Syber Green. Minimum inhibitory concentrations (MICs) of the hydroethanolic extract against Salmonella strains were higher than 2000 μg/mL. This extract was active against multidrug-resistant Plasmodium falciparum strains (PfDd2) with an inhibitory concentration (IC50) of 32.26 μg/mL. These works on Rourea coccinea justify that the plant has a clearly remarkable antiplasmodial activity rather than anti-salmonella one and its use in traditional medicine to treat malaria in Benin.

Structure-activity relationship of anticancer and antiplasmodial gold bis(dithiolene) complexes.

Monoanionic gold bis(dithiolene) complexes were recently shown to display activity against ovarian cancer cells, Gram-positive bacteria, Candida strains and the rodent malaria parasite, P. berghei. To date, only monoanionic gold(III) bis(dithiolene) complexes with a thiazoline backbone substituted with small alkyl chains have been evaluated for biomedical applications. We now analyzed the influence of the length and the hydrophobicity vs. hydrophilicity of these complexes' alkyl chain on their anticancer and antiplasmodial properties. Isomer analogues of these monoanionic gold(III) bis(dithiolene) complexes, this time with a thiazole backbone, were also investigated in order to assess the influence of the nature of the heterocyclic ligand on their overall chemical and biological properties. In this report we present the total synthesis of four novel monoanionic gold(III) bis(dithiolene) complexes with a long alkyl chain and a polyoxygenated (PEG) chain aiming to improve their solubility and biological properties. Our results showed that the complexes with a PEG chain showed promising anticancer and antiplasmodial activities beside improved solubility, a key parameter in drug discovery and development.

Biosynthesis, biological activities, and structure-activity relationships of decalin-containing tetramic acid derivatives isolated from fungi.

Covering: up to December 2023Decalin-containing tetramic acid derivatives, especially 3-decalinoyltetramic acids (3-DTAs), are commonly found as fungal secondary metabolites. Numerous biological activities of this class of compounds, such as antibiotic, antiviral, antifungal, antiplasmodial, and antiprotozoal properties, have been the subject of ongoing research. For this reason, these molecules have attracted a lot of interest from the scientific community and various efforts including semi-synthesis, co-culturing with bacteria and biosynthetic gene sequencing have been made to obtain more derivatives. In this review, 3-DTAs are classified into four major groups based on the absolute configuration of the bicyclic decalin ring. Their biosynthetic pathways, various biological activities, and structure-activity relationship are then introduced.