Potential Antimalarials Research Articles

Exploring Potential Antimalarial Candidate from Medicinal Plants of Kheaw Hom Remedy.

The Kheaw Hom remedy is a traditional Thai medicine widely used to treat fevers. Some plant ingredients in this remedy have been investigated for their antimicrobial, antiviral, anti-inflammatory, and antioxidant activities. However, there have been no reports on the antimalarial activities of the medicinal plants in this remedy. Therefore, this study focuses on identifying potential antimalarial drug candidates from the medicinal plant ingredients of the Kheaw Hom remedy. Eighteen plants from the Kheaw Hom remedy were extracted using distilled water and ethanol. All extracts were investigated for their in vitro antimalarial activity and cytotoxicity. An extract that exhibited good in vitro antimalarial activity and low toxicity was selected for further investigation by using Peter's 4-day suppressive test and an acute oral toxicity evaluation in mice. Based on the in vitro antimalarial activity and cytotoxicity studies, the ethanolic extract of Globba malaccensis rhizomes showed promising antimalarial activity against the Plasmodium falciparum K1 strain (IC50 = 1.50 µg/mL) with less toxicity to Vero cells (CC50 of >80 µg/mL). This extract exhibited a significant dose-dependent reduction in parasitemia in P. berghei-infected mice. The maximum suppressive effect of this extract (60.53%) was observed at the highest dose administered (600 mg/kg). In a single-dose acute toxicity test, the animals treated at 2000 mg/kg died within 48 h after extract administration. In conclusion, our study indicates that the ethanolic extract of G. malaccensis rhizomes exhibited in vitro and in vivo antimalarial activities, which could serve as a promising starting point for antimalarial drug.

The potency of plant antimalarial

Malaria has remained a major cause of morbidity and mortality in all parts of the world. It is associated with high economic burden on the nation, high prevalence of mortality in children, pregnant women and non-immune individuals, thus malaria is a global public health problem. This protozoan infection is mainly characterized by fever, pains, loss of appetite and anaemia, researchers had discovered potent antimalarial drugs mainly from plant sources in order to overcome resistance of antimalarials, vectors, inability to develop malarial vaccines and also toxic effects of conventional antimalarial drugs. Antimalarials obtained from plants have significant roles in drug discovery and development for the treatment of fever, pains, inflammation as well as Plasmodium falciparum infection, therefore this review focuses on the analgesics, antipyretics and anti-inflammatory activities as well as antiplasmodial activities of plants.

Uncovering the antimalarial potential of toad venoms through a bioassay-guided fractionation process

Malaria remains to date one of the most devastating parasitic diseases worldwide. The fight against this disease is rendered more difficult by the emergence and spread of drug-resistant strains. The need for new therapeutic candidates is now greater than ever. In this study, we investigated the antiplasmodial potential of toad venoms. The wide array of bioactive compounds present in Bufonidae venoms has allowed researchers to consider many potential therapeutic applications, especially for cancers and infectious diseases. We focused on small molecules, namely bufadienolides, found in the venom of Rhinella marina (L.). The developed bio-guided fractionation process includes a four solvent-system extraction followed by fractionation using flash chromatography. Sub-fractions were obtained through preparative TLC. All samples were characterized using chromatographic and spectrometric techniques and then underwent testing on in vitro Plasmodium falciparum cultures. Two strains were considered: 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant). This strategy highlighted a promising activity for one compound named resibufogenin. With IC50 values of (29 ± 8) μg/mL and (23 ± 1) μg/mL for 3D7 and W2 respectively, this makes it an interesting candidate for further investigation. A molecular modelling approach proposed a potential binding mode of resibufogenin to Plasmodium falciparum adenine-triphosphate 4 pump as antimalarial drug target.

Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2.

New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 (2) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 (PfeEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline (2) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency.

Antimalarial potential of compounds isolated from Mammea siamensis T. Anders. flowers: in vitro and molecular docking studies

Background:The emergence of antimalarial drug resistance encourages the search for new antimalarial agents. Mammea siamensis belongs to the Calophyllaceae family, which is a medicinal plant that is used in traditional Thai preparations. The hexane and dichloromethane extracts of this plant were found to have potent antimalarial activity. Therefore, this study aimed to isolate active compounds from M. siamensis flowers and evaluate their antimalarial potential and their interactions with Plasmodium falciparum lactate dehydrogenase (PfLDH).Methods:The compounds from M. siamensis flowers were isolated by chromatographic techniques and evaluated for their antimalarial activity against chloroquine (CQ)-resistant P. falciparum (K1) strains using a parasite lactate dehydrogenase (pLDH) assay. Interactions between the isolated compounds and the PfLDH enzyme were investigated using a molecular docking method.Results:The isolation produced the following thirteen compounds: two terpenoids, lupeol (1) and a mixture of β-sitosterol and stigmasterol (5); two mammea coumarins, mammea A/AA cyclo D (6) and mammea A/AA cyclo F (7); and nine xanthones, 4,5-dihydroxy-3-methoxyxanthone (2), 4-hydroxyxanthone (3), 1,7-dihydroxyxanthone (4), 1,6-dihydroxyxanthone (8), 1-hydroxy-5,6,7-trimethoxyxanthone (9), 3,4,5-trihydroxyxanthone (10), 5-hydroxy-1-methoxyxanthone (11), 2-hydroxyxanthone (12), and 1,5-dihydroxy-6-methoxyxanthone (13). Compound 9 exhibited the most potent antimalarial activity with an IC50 value of 9.57 µM, followed by 10, 1, 2 and 13 with IC50 values of 15.48, 18.78, 20.96 and 22.27 µM, respectively. The molecular docking results indicated that 9, which exhibited the most potent activity, also had the best binding affinity to the PfLDH enzyme in terms of its low binding energy (-7.35 kcal/mol) and formed interactions with ARG109, ASN140, and ARG171.Conclusion:These findings revealed that isolated compounds from M. siamensis flowers exhibited antimalarial activity. The result suggests that 1-hydroxy-5,6,7-trimethoxyxanthone is a possible lead structure as a potent inhibitor of the PfLDH enzyme.

Inhibitors of ApiAP2 protein DNA binding exhibit multistage activity against Plasmodium parasites.

Plasmodium parasites are reliant on the Apicomplexan AP2 (ApiAP2) transcription factor family to regulate gene expression programs. AP2 DNA binding domains have no homologs in the human or mosquito host genomes, making them potential antimalarial drug targets. Using an in-silico screen to dock thousands of small molecules into the crystal structure of the AP2-EXP (Pf3D7_1466400) AP2 domain (PDB:3IGM), we identified putative AP2-EXP interacting compounds. Four compounds were found to block DNA binding by AP2-EXP and at least one additional ApiAP2 protein. Our top ApiAP2 competitor compound perturbs the transcriptome of P. falciparum trophozoites and results in a decrease in abundance of log2 fold change > 2 for 50% (46/93) of AP2-EXP target genes. Additionally, two ApiAP2 competitor compounds have multi-stage anti-Plasmodium activity against blood and mosquito stage parasites. In summary, we describe a novel set of antimalarial compounds that interact with AP2 DNA binding domains. These compounds may be used for future chemical genetic interrogation of ApiAP2 proteins or serve as starting points for a new class of antimalarial therapeutics.

Structural, Spectroscopic, and Molecular Docking Analysis of Benzophenone N(4)-methyl-N(4)-phenyl Thiosemicarbazone Using Density Functional Theory

A new thiosemicarbazone derivative, benzophenone N(4)-methyl-N(4)-phenyl thiosemicarbazone (BMPT) is synthesized using benzophenone and N(4)-methyl-N(4)- phenylthiosemicarbazide as precursors. Synthesized ligand is characterized by Fourier Transform Infrared spectra (FTIR) and FT-Raman spectra. Complete quantitative assignments of vibrational modes are presented in terms of potential energy distribution (PED) using quantum chemical calculations using the density functional theory (DFT) approach. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) surface analysis are used to estimate the correlation between molecular structure and biological activity at the electronic level. Hirshfeld surface analysis is used to interpret the intermolecular interactions and also to provide information about the percentage contribution of various intermolecular contacts in the crystal structure. Besides the above, molecular docking studies of BMPT ligand with 3RGF and 3EWD proteins are also performed to confirm the ability of BMPT ligand as an active pharmaceutical ingredient (API) of potential anticancer and antimalarial drugs.

Synthesis and in vitro SAR evaluation of natural vanillin-based chalcones tethered quinolines as antiplasmodial agents

A series of novel chalcone derivatives were synthesized and investigated against the chloroquine-sensitive P. falciparum 3D7 (Pf3D7) strain and chloroquine-resistant P. falciparum K1 strain to establish their structure-activity relationship. In this study, compound 7 was found most active as well as less cytotoxic (IC50 = 4.12 µM and 3.14 µM for Pf3D7 and PfK1 respectively; CC50 = 46.18 µM). Compound 7 was studied for effect on parasite growth and the microscopic examination showed excessive DNA damage in the trophozoite stage. The parasite recovery after drug removal was poor due to the dramatic genotoxic effect of compound 7. It suggested that 7-chloro quinoline and triazole linkage were crucial for antimalarial potential. Graphical abstract

Ethnobotanical Study of Plants Used by Traditherapists for the Treatment of Malaria in the City of Butembo, North Kivu, East of the Democratic Republic of Congo

Malaria is a serious public health problem in the Democratic Republic of Congo (DRC) in general and in the city of Butembo in particular. To complete the lack of information, the objective of this article is to identify the different plant species used in the traditional treatment of malaria in the city of Butembo. Ethnobotanical investigations were conducted among 91 traditherapists. Semi-structured interviews with the use of a pre-established questionnaire were used for data collection. This study allowed the inventory of 26 plant species belonging to 18 botanical families. The species of the Asteraceae family are the most solicited by the therapists of the city of Butembo (25.27%). This family is followed by the Myrtaceae and Rubiaceae families, each with a total of 12.09%. Then come the Caricaceae, Poaceae, and Fabaceae with respectively 9.89%, 9.89%, and 8.79% of citations. Leaves are the most used organ (70.33%) in the preparation of drugs. The pharmaceutical form of preparation is decoction (81.32%). The antimalarial recipes are administered by oral (100%). The species most solicited by the therapists are Artemisia annua (12.09%), Eucalyptus maideni var globulus (10.99%), Cinchona ledgeriana (10.99%), Cymbopogon citratus (9.89%), Carica papaya (9.89%), Cassia occidentalis (7.69%), and Bidens pilosa (8.79%). In consideration of these results, phytochemical and pharmacological analysis of these plants is essential to help validate their traditional use and to find new plants with antimalarial potential that would play the first role in the development of improved traditional medicines (ITM) with antimalarial activity.

Evaluation of antiplasmodial activity and inhibitions of lipid peroxidation and parasite haem polymerization activity by medicinal phytochemicals of Phyllanthus amarus

Despite the dedicated struggle to eliminate malaria, the current trend of the infection, particularly, in sub-Saharan Africa remains worrisome due to failing control and treatment approaches caused by a myriad of factors. Therefore, the search for new, affordable, and more potent antimalarial drugs, from plants especially, have become the frontline in recent times. This study thus, evaluates the in vitro antiplasmodial, cytotoxic and antioxidant activities of the phytochemical (alkaloids, flavonoids, tannins, saponins, cardiac glycosides and anthraquinones) extracts of Phyllanthus amarus using documented methods. Antiplasmodial and cytotoxic activities were determined by parasite growth inhibition assay and microassay technique by the lactate dehydrogenase method, respectively. Antioxidant activities were determined by measuring inhibition of both lipid peroxidation and heam polymerization by extracts. Results show that the alkaloid extract was noncytotoxic (CC = 60.26 μg/mL) and most selectable (SI = 125.5) with the highest antiplasmodial (IC = 0.48 μg/mL) and 50 50 haem polymerization inhibition (IC = 0.63 μg/mL) activities, but moderate antioxidant lipid peroxidation inhibition, (LPI; 50 IC = 500μg/mL) capacity. However, the ethanol and flavonoid phytochemical extracts displayed the highest antioxidant 50 activity in inhibition of heam polymerization (IC = 0.46 μg/mL) and lipid peroxidation (IC = 218.78 μg/mL), respectively, 50 50 with significant antiplasmodial activity (IC = 0.48 μg/mL and 1.10 μg/mL, respectively). Our results show that all 50s phytochemical extracts studied were non-cytotoxic. Although the antioxidant activities of the flavonoid and ethanol phytochemical extracts were greater in comparison to the alkaloid phytochemical, alkaloid was the most selectable active antiplasmodial phytochemical of P. amarus and one of its mechanisms of action is by inhibiting parasite haem detoxification.

N-sulfonylpiperidinedispiro-1,2,4,5-tetraoxanes exhibit potent in vitro antiplasmodial activity and in vivo efficacy in mice infected with P. berghei ANKA

The artemisinin resistance has posed a serious threat against malaria elimination lately. Past few years have seen important development of several peroxide based medicinal compounds and their derivatives such as trioxanes and tetraoxanes. Here, we report a rapid, one-pot method for synthesizing a new series of N-sulfonylpiperidine dispiro-1,2,4,5-tetraoxane analogs with diverse substitution on the tetraoxane ring i.e., various substituted alkyl and aryl sulfonyl chlorides, as well as cyclic, acyclic and aryl substituted ketones. All the synthesized tetraoxanes were characterized by spectroscopic (1H NMR,13C NMR), and spectrometric (High-resolution mass spectrometry) techniques and quantify by High Performance Liquid Chromatography (HPLC) analysis. The structure of compound 19 was confirmed by single crystal XRD. From the overall preliminary in vitro data, analogs 14, 16, 19, 20, 24, 41, and 44 exhibited potential IC50 values in the nanomolar range between 4.7 ± 0.3 to 12.9 ± 1.1 nM against P. falciparum (Pf3D7) strains of human malaria parasite. Furthermore, these selective analogs were evaluated in vivo for their antimalarial potential against P. berghei and results revealed that analogue 24 rapidly kills the infected cell at asexual erythrocytic stage, with activity comparable to positive control chloroquine.

In silico Evaluation of the Antimalarial Potential of the Phytoconstituents of the Azadirachta indica Plant

Background and Objectives: Malaria, a parasitic protozoan disease caused primarily by Plasmodium falciparum, has killed millions of people in Africa, particularly those with meager or no access to orthodox medical facilities and therapies. Extracts from the Azadirachta indica (neem) plant is believed to possess antimalaria properties among the locals that rely on herbs. Numerous in - vivo studies have suggested the antimalarial properties of neem extract and phytochemicals. This study employs an in - silico method through molecular docking techniques to provide insight while adding credence to the antimalarial potential of phytochemicals of neem plants as claimed in folkloric medicine. Methods: – The crystal structure of Plasmodium falciparum a causative parasite of malaria was retrieved from the Protein Data Bank, and Azadirachta indica phytochemicals were obtained from the PubChem database. Molecular docking through virtual screening was carried out on the characterized phytochemicals. The bioactive compounds from the Azadirachta indica plant were investigated by docking with the crystal structure of Plasmodium falciparum receptor and compared with standard antimalarial drugs (lumenfrantrine and artemisinin). Results: - Three Azadirachta indica phytochemicals (gedunnin, nimbinene and salanin) shows a competing binding energy and affinity when compared to the approved antimalarial drugs (lumefrantrine and artemisinin). while the binding energies for azadirachtin, nimbandiol and quercetin is lower than the value obtained in artemisinin but comparable with lumefrantrine. Conclusion: This virtual screening verified and identified a potential phytochemical component of antimalarial properties against a protein target: 1m7o, Plasmodium falciparum triosephosphate isomerase (PfTIM)

In silico Evaluation of the Antimalarial Potential of the Phytoconstituents of the Azadirachta indica Plant

In silico Evaluation of the Antimalarial Potential of the Phytoconstituents of the Azadirachta indica Plant

Toxicological Analysis and Antimalarial Potentials of Secondary Metabolites of Curvularia lunata, an Endophyte Obtained from the Leaves of Azadirachta indica

Toxicological Analysis and Antimalarial Potentials of Secondary Metabolites of Curvularia lunata, an Endophyte Obtained from the Leaves of Azadirachta indica

Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives

BackgroundThe search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malarial property.MethodsHere, in vivo prophylactic and curative activities of the compounds were assessed while their binding affinity for falcipain-2, a crucial enzyme in Plasmodium survival, was done using computational techniques.ResultsThe two derivatives (BepINH and BepBeH) respectively led to a significant (p < 0.05) reduction in parasitaemia count (0.76 ± 1.11 and 0.79 ± 1.19) at day 3 post-treatment relative to the negative control (16.37 ± 1.25). For the prophylactic study, it was observed that the highest parasitaemia suppression level of 95.35% and 95.17% for BepINH and BepBeH at 15 mg/kg was slightly comparable to that obtained for ACT-Lonart (99.38%). In addition, their haematological profiles indicate that they are potentially beneficial in suppressing haemolytic damage to RBC, thereby protecting the body against infection-induced anaemia. Docking calculations on the derivatives toward the Plasmodium falciparum falcipain-2 revealed that they favourably interacted with a binding affinity higher than that of a known cocrystallized inhibitor.ConclusionThis study confirms the relevance of multi-functional molecules in the search for new and effective anti-plasmodial agent and lay the foundation for further development of these compound series to potent anti-plasmodial agent that interacts with falcipain-2.

Ellagic Acid Induces in vitro Alkalinisation of the Digestive Vacuole in Drug-Sensitive Plasmodium falciparum Strain.

BackgroundMalaria is one of the leading causes of death worldwide caused by parasites of the genus Plasmodium. The reduced efficacy of the mainstay antimalarial drugs due to the widespread of drug-resistant Plasmodium falciparum (P. falciparum) necessitates an effort to develop novel antimalarial drugs with new targets. The effects of a phenolic compound, ellagic acid, against the malaria parasite have previously been reported. This present study aimed to evaluate the effect of ellagic acid on pH of the P. falciparum digestive vacuole.MethodsThe antimalarial potential of ellagic acid against the chloroquine-sensitive strain (3D7) of P. falciparum was assessed by using a malarial SYBR Green 1 fluorescence-based (MSF) assay. The effect of different concentrations of ellagic acid on the pH of the parasite’s digestive vacuole at mid-trophozoite stage was examined by using a ratiometric pH indicator, fluorescein isothiocyanate (FITC)-dextran on the flow cytometry.ResultsThe result of the MSF assay showed that ellagic acid has an antimalarial activity (half-maximal inhibitory concentration [IC50] = 1.85 ± 4.57 nM) at par with a standard drug, artemisinin (IC50 = 1.91 ± 5.41 nM). The pH of the digestive vacuole of ellagic acid-treated parasites was significantly changed (pH values ranged from 6.11 to 6.74) in a concentration-dependent manner as compared to untreated parasites (P < 0.001). A similar effect was shown by the parasites treated with a standard proton pump inhibitor, concanamycin A.ConclusionThese findings suggest that ellagic acid might have altered the digestive vacuole pH through the inhibition of proton pumps that regulate the acidification of this organelle. Overall, this study provides a valuable insight into the potential of ellagic acid as a promising antimalarial candidate with a novel mechanism of action.

In vivo chemosuppressive activities of combinations of four Nigerian ethnomedicinal antimalarial ferns

Background to the study: The in vivo antimalarial activities and the effects of combining the methanol extracts of four ferns namely, Nephrolepis biserrata (NB), N. undulata (NU), Platycerium stemaria (PS), and P. angolense (PA) randomly and with chloroquine, was determined. Methods: The four ferns were collected, separately air-dried, powdered and the extracts was obtained by cold maceration with methanol and evaporation in vacuo. They were subsequently investigated (0-800mg/kg) for antimalarial potency against chloroquine-sensitive Plasmodium berghei berghei in mice using the Peters’ four-day test after preliminary toxicity studies, using Lorke’s method. They were further tested separately, combined with chloroquine and randomly combined with each other at their respective median effective doses. Result: NB and PS elicited comparable ED50 and lower activities than NU while PA was the least active. The percentage chemosuppression elicited by all the individual extracts were comparable [p&gt;0.05] to that of chloroquine when combined, with chloroquine and each other, except for NU and PS. Also, NB+PA, NB+PS, NU+PA+PS, NU+NB+PS and NU+NB+PA gave comparable [p&gt;0.05] chemosuppression to CQ. However, NU+PA, NU+CQ and PS+CQ elicited similar survival times and % survivor with chloroquine. The activities of the lower - acting PA and PS was only improved by combination with either NU or NB and did not give better effects than the most active individual drug. Conclusion: The study confirms the ethnomedicinal use of NU and NB for malaria and indicate that combining the ferns did not give any significant increase in activity better than the most active individual or the standard drug.

A review of the antimalarial and antidiabetic potential of Moringa oleifera

A review of the antimalarial and antidiabetic potential of Moringa oleifera

A review of the antimalarial and antidiabetic potential of Moringa oleifera

A review of the antimalarial and antidiabetic potential of Moringa oleifera

A review of the antimalarial and antidiabetic potential of Moringa oleifera

A review of the antimalarial and antidiabetic potential of Moringa oleifera