Promising Antimalarial Activity Research Articles

Expanding the occurrence of antimalarial metabolites in dorid nudibranch Hypselodoris tryoni

This study examined the antimalarial activity of a furanosesquiterpene, furodysinin, one of the major metabolites of the dorid nudibranch Hypselodoris tryoni. The nudibranchs were collected from Balinese waters and the metabolites were purified by chromatography. Ex vivo rodent malaria Plasmodium berghei assays were conducted to determine the metabolite antimalarial activity. In silico molecular docking was employed to investigate the interaction between furodysinin against wild-type P. berghei and atovaquone-resistant P. berghei (Y268C). This study reported for the first time that the furodysinin displayed a promising antimalarial activity based on the ex vivo tests against wild-type P. berghei and atovaquone-resistant P. berghei. In silico molecular docking study showed that furodysinin inhibits the parasite mitochondrial cytochrome b (cyt b) by binding to the protein Qo pocket (ef-helix) where it interacts with residue 268, the mutation of which is known to confer resistance to atovaquone. Furodysinin binds to the mutated tyrosine at residue 268, which has changed to cysteine, forming an alkyl bond with C268 at a distance of 4.6 Å. Therefore, we predict that furodysinin has a target in Plasmodium mitochondria.

Discovery of antimalarial drugs from secondary metabolites in actinomycetes culture library

BackgroundNatural products play a key role as potential sources of biologically active substances for the discovery of new drugs. This study aimed to identify secondary metabolites from actinomycete library extracts that are potent against the asexual stages of Plasmodiumfalciparum (P.falciparum).MethodsSecondary metabolites from actinomycete library extracts were isolated from culture supernatants by ethyl acetate extraction. Comprehensive screening was performed to identify novel antimalarial compounds from the actinomycete library extracts (n = 28). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) lines of P.falciparum. The cytotoxicity was then evaluated in primary adult mouse brain (AMB) cells.ResultsOut of the 28 actinomycete extracts, 17 showed parasite growth inhibition > 50% at a concentration of 50 µg/mL, nine were identified with an IC50 value < 10 µg/mL, and seven suppressed the parasite significantly with an IC50 value < 5 µg/mL. The extracts from Streptomycesaureus strains HUT6003 (Extract ID number: 2), S.antibioticus HUT6035 (8), and Streptomyces sp. strains GK3 (26) and GK7 (27), were found to have the most potent antimalarial activity with IC50 values of 0.39, 0.09, 0.97, and 0.36 µg/mL (against 3D7), and 0.26, 0.22, 0.72, and 0.21 µg/mL (against Dd2), respectively. Among them, Streptomycesantibioticus strain HUT6035 (8) showed the highest antimalarial activity with an IC50 value of 0.09 µg/mL against 3D7 and 0.22 µg/mL against Dd2, and a selective index (SI) of 188 and 73.7, respectively.ConclusionSecondary metabolites obtained from the actinomycete extracts showed promising antimalarial activity in vitro against 3D7 and Dd2 cell lines of P.falciparum with minimal toxicity. Therefore, secondary metabolites obtained from actinomycete extracts represent an excellent starting point for the development of antimalarial drug leads.

1,2,4,5-Tetraoxane derivatives/hybrids as potent antimalarial endoperoxides: Chronological advancements, structure-activity relationship (SAR) studies and future perspectives.

Malaria is a life-threatening disease that affects tropical and subtropical regions worldwide. Various drugs were used to treat malaria, including artemisinin and derivatives, antibiotics (tetracycline, doxycycline), quinolines (chloroquine, amodiaquine), and folate antagonists (sulfadoxine and pyrimethamine). Since the malarial parasites developed drug resistance, there is a need to develop new chemical entities with high efficacy and low toxicity. In this context, 1,2,4,5-tetraoxanes emerged as an essential scaffold and have shown promising antimalarial activity. To improve activity and overcome resistance to various antimalarial drugs; 1,2,4,5-tetraoxanes were fused with various aryl/heteroaryl/alicyclic/spiro moieties (steroid-based 1,2,4,5-tetraoxanes, triazine-based 1,2,4,5-tetraoxanes, aminoquinoline-based 1,2,4,5-tetraoxanes, dispiro-based 1,2,4,5-tetraoxanes, piperidine-based 1,2,4,5-tetraoxanes and diaryl-based 1,2,4,5-tetraoxanes). The present review aims to focus on covering the relevant literature published during the past 30 years (1992-2022). We summarize the most significant in vitro, in vivo results and structure-activity relationship studies of 1,2,4,5-tetraoxane-based hybrids as antimalarial agents. The structural evolution of different hybrids can provide the framework for the future development of 1,2,4,5-tetraoxane-based hybrids to treat malaria.

In Vitro Analysis of Antimalarial Activity of Achillea fragrantissima (Forssk.) Sch.Bip Extracts Based on Beta-Hematin Formation

Introduction: The use of medicinal plants from traditional knowledge systems has increased in recent years. Achillea fragrantissima-infused water has a historical use in relieving gastrointestinal complaints and treating skin inflammations. With the rising resistance to antimalarial drugs, finding safe and affordable new drugs is crucial. Exploring medicinal plants shows promise for drug development in the fight against malaria. Methods: The objective of this research is to examine the in vitro antimalarial activity of A. fragrantissima-infused water, as well as water-ethanol extracts of its leaves, flowers, and stems based on β-hematin formation. Colorimetric semiquantitative assessments based on β-hematin inhibition and evaluation of optical density at 405 nm were employed. Results: The results demonstrated promising antimalarial activity of the different plant parts. The aqueous flower extract exhibited strong activity, comparable to that of the positive control. The leaves extract also showed strong antimalarial activity. The stem's aqueous and ethanolic extracts exhibited lower inhibitory activity compared to flowers and leaves. Synergistic antimalarial activity was observed when mixing the stem and leaves water extracts, as well as when mixing each of the stem and leaves extracts with the flower extract. The highest synergistic effect was observed when all three parts of the plant were mixed, resulting in activity comparable to the positive control. The high-performance liquid chromatography photodiode array (HPLC-PDA) chromatographic method confirmed the presence of rutin in the leaves extract. Conclusion: The findings of this study highlight the potential antimalarial activity of A. fragrantissima. The aqueous flower extract and leaves extract exhibited strong antimalarial activity, while the stem extracts showed relatively lower activity. Furthermore, synergistic effects were observed when combining different parts of the plant. These results suggest that A. fragrantissima holds promise as a potential source for the development of new antimalarial drugs. The confirmation of rutin presence in the leaves extract through HPLC-PDA analysis provides additional insights into the plant's chemical composition.

Design, synthesis and Anti-Plasmodial activity of Mortiamide-Lugdunin conjugates

In this study, two linear and corresponding cyclic heptapeptide versions of mortiamide A-lugdunin hybrids were designed and synthesized by integrating an anti-malarial peptide epitope derived from Mortiamide A, combined with four residues known for their membrane interactions. Using this synthetic strategy, the sequence of mortiamide A was partly re-engineered with an epitope sequence of lugdunin along with an amino acid replacement using all-L and D/L configurations. Importantly, the re-engineered cyclic mortiamides with all-L (3) and D/L (4) configurations exhibited promising anti-malarial activities against the P. falciparum drug-sensitive TM4/8 strain with half-maximal inhibitory concentration (IC50) values of 6.2 ± 0.5 and 4.8 ± 0.1 μM, respectively. Additionally, they exhibited anti-malarial activities against the P. falciparum multidrug-resistant V1/S strain with IC50 values of 5.0 ± 2.6 and 3.7 ± 0.7 μM, respectively. Interestingly, a linear re-engineered mortiamide with D/L configuration (2) exhibited promising anti-malarial activities, surpassing those of the re-engineered cyclic mortiamides (3 and 4), against both the P. falciparum sensitive TM4/8 and multidrug-resistant V1/S strains with IC50 values of 3.6 ± 0.5 and 2.8 ± 0.7 μM (IC50 of Mortiamide A = 7.85 ± 0.97, 5.31 ± 0.24 μM against 3D7 and Dd2 strains) without any cytotoxicity at >100 µM. The presence of D/L forms in a linear structure significantly impacted the anti-malarial activity against both the P. falciparum sensitive TM4/8 strain and the multidrug-resistant V1/S strain.

Novel ether derivatives of 11-azaartemisinins with high order antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice

This study investigates cutting-edge synthetic chemistry approaches for designing and producing innovative antimalarial drugs with improved efficacy and fewer adverse effects. Novel amino (–NH2) and hydroxy (–OH) functionalized 11-azaartemisinins 9, 12, and 14 were synthesized along with their derivatives 11a, 13a-e, and 15a-b through ART and were tested for their AMA (antimalarial activity) against Plasmodium yoelii via intramuscular (i.m.) and oral routes in Swiss mice. Ether derivative 13c was the most active compound by i.m. route, it has shown 100 % protection at the dose of 12 mg/kg × 4 days and showed 100 % clearance of parasitaemia on day 4 at dose of 6 mg/kg. Amine 11a, ether derivatives 13d, 13e and ether 15a also showed promising antimalarial activity. β-Arteether gave 100 % protection at the dose of 48 mg/kg × 4 days and 20 % protection at 24 mg/kg × 4 days dose by oral route, while it showed 100 % protection at 6 mg/kg × 4 days and no protection at 3 mg/kg × 4 days by i.m. route.

Chemoproteomics-based profiling reveals potential antimalarial mechanism of Celastrol by disrupting spermidine and protein synthesis

BackgroundMalaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive.MethodsWe first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays.ResultsThe results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects.ConclusionsIn conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel.5LH6oqsCtKBdVDis1L_PeKVideo

Alkaloids as Antimalarial Compounds: A Review of Recent Studies

Abstract: Malaria is a parasitic infection caused by Plasmodium parasites that are transmitted to humans through the bite of infected Anopheles mosquitoes. Malaria continues to contribute unacceptably high rates of sickness and death. Natural product compounds have long been recognized as one of valuable natural remedy resources with promising structural motif pools for the development of first-line drugs. Resistance to conventional treatments such as chloroquine, mefloquine, and artemisinin- based combination therapy (ACT) by the causal agent, the Plasmodium parasite, is a major concern in malaria treatment and prevention globally. Given the parasites' resistance to several current treatment regimens, innovative antimalarial chemotherapeutic medicines derived from tetramic acid alkaloids are desperately needed. In this review, new and old antimalarial alkaloids identified and reported recently from 2017 to 2021 are presented. Several compounds with promising antimalarial activity are identified from several subclasses of alkaloids. It is hoped that this review report will inspire future research into the compounds' toxicity and in vivo efficacy, to exploit this intriguing compound as antimalarial drugs.

Potential of medicinal plants as antimalarial agents: a review of work done at Kenya Medical Research Institute.

Background: Medicinal plants have traditionally been used as remedies against malaria. The present review attempted to compile data on scientific research evidence on antimalarial medicinal plants screened at Kenya Medical Research Institute (KEMRI), Center for Traditional Medicine and Drug (CTMDR) Research from January 2003 to December 2021. Methods: A systematic review was conducted using a predefined protocol based on PRISMA. Search was performed in Google Scholar and PubMed. One hundred and eight journal articles were identified 37 of which published on antimalarial/antiplasmodial work. Thirty journal articles with at least one author from KEMRI-CTMDR and accessible in full were selected for analysis. Relevant data was captured in MS Excel format and descriptive statistics, percentages and tables used to summarize the findings. Results: Assessment of individual plant species was considered as an independent study resulting in 1170 antiplasmodial/antimalarial tests done from 197 plant species. One hundred and fifty plant species were screened in vitro, one in vivo and 46 were both in vivo and in vitro. Three hundred and forty-four of tests reported good activity (IC50 < 10μg/mL or parasite suppression rate of ≥50%), 414 moderate activity (IC50 values of 10-49μg/mL or parasite suppression rate of 30%-49%) and 412 were reports of inactivity (IC50 ˃ 50μg/mL or parasite suppression rate of <30%). Fuerstia africana and Ludwigia erecta were reported to have the highest activities, with IC50 < 1μg/mL against Plasmodium falciparum D6 strain and chemosuppression in mice at an oral dose of 100mg/kg, was reported as 61.9% and 65.3% respectively. Fifty five antimalarial/antiplasmodial active compounds isolated from eight plant species were reported with resinone (39) having the best activity (IC50 < 1μg/mL). Conclusion: Though 344 of tests reported promising antimalarial activity, it was noted that there was limited evaluation of these plants in animal models, with only 9.0% (105/1170) studies and no clinical trials. This highlights an important research gap emphasizing the need for drug development studies that aim to progress study findings from preclinical to clinical studies. There is still need for extensive research on promising plant species aimed at developing new plant based antimalarial drugs.

Antimalarial Activity of Anacardium occidentale Leaf Extracts Against Plasmodium falciparum Transketolase (PfTK).

As per estimates by WHO in 2021 almost half of the world's population was at risk of malaria and > 0.6 million deaths were attributed to malaria. Therefore, the present study was aimed to explore the antimalarial activity of extracts derived from the leaves of the plant Anacardium occidentale L., which has been used traditionally for the treatment of malaria. Different extracts of A. occidentale leaves were prepared and tested for their inhibitory activity against recombinant P. falciparum transketolase (rPfTK) enzyme, in vitro. Further, growth inhibitory activity against cultivated blood stage P. falciparum parasites (3D7 strain), was studied using SYBR Green fluorescence-based in vitro assays. Acute toxicity of the hydro alcoholic extracts of leaves of A. occidentale (HELA) at different concentrations was evaluated on mice and Zebra fish embryos. HELA showed 75.45 ± 0.35% inhibitory activity against the recombinant PfTk and 99.31 ± 0.08% growth inhibition against intra-erythrocytic stages of P. falciparum at the maximum concentration (50µg/ml) with IC50 of 4.17 ± 0.22µg/ml. The toxicity testresults showed that the heartbeat, somite formation, tail detachment and hatching of embryos were not affected when Zebra fish embryos were treated with 0.1 to 10µg/ml of the extract. However, at higher concentrations of the extract, at 48h (1000µg/ml) and 96h (100µg/ml and 1000µg/ml, respectively) there was no heartbeat in the fish embryos. In the acute oral toxicity tests performed on mice, the extract showed no toxicity up to 300mg/kg body weight in mice. The hydro-alcoholic extract of leaves of A. occidentale L. showed potent antimalarial activity against blood stage P. falciparum. Based on the observed inhibitory activity on the transketolase enzyme of P. falciparum it is likely that this enzyme is the target for the development of bioactive molecules present in the plant extracts. The promising anti-malarial activity of purified compounds from leaves of A. occidentale needs to be further explored for development of new anti-malarial therapy.

Incorporation of Trifluoromethyltriazoline in the Side Chain of 4-Aminoquinolines: Synthesis and Evaluation as Antiplasmodial Agents.

Reported herein is the identification of a novel class of 4-aminoquinoline-trifluormethyltriazoline compounds as possible antiplasmodial agents. The compounds were accessed through a silver-catalyzed three-component reaction of trifluorodiazoethane with in situ generated Schiff base from corresponding quinolinylamine and aldehydes. While attempting to incorporate a sulfonyl moiety, the triazoline formed underwent spontaneous oxidative aromatization to afford triazole derivatives. All synthesized compounds were tested for their antimalarial potential in vitro and in vivo. Out of 32 compounds, four showed the most promising antimalarial activity with IC50 values ranging from 4 to 20 nM against Pf3D7 (chloroquine-sensitive) and from 120 to 450 nM against PfK1 (chloroquine-resistant) strains. One of these compounds was also found to be effective in animal studies; it showed a 99.9 % decrease in parasitic load on day 7 post-infection along with a 40 % cure rate and longest host life span.

Rational Design and Lead Optimisation of Potent Antimalarial Quinazolinediones and Their Cytotoxicity against MCF-7.

Quinazolinedione is one of the most outstanding heterocycles in medicinal chemistry thanks to its wide ranges of biological activities including antimalarial, anticancer, and anti-inflammatory. TCMDC-125133 containing a quinazolinedione pharmacophore displays promising antimalarial activity and low toxicity, as described in the GlaxoSmithKline (GSK) report. Herein, the design and synthesis of novel quinazolinedione derivatives is described on the basis of our previous work on the synthesis of TCMDC-125133, where low-cost chemicals and greener alternatives were used when possible. The initial SAR study focused on the replacement of the valine linker moiety; according to the in silico prediction using SwissADME, concise four-step syntheses toward compounds 4-10 were developed. The in-house synthesized compounds 4-10 were assayed for antimalarial activity against P. falciparum 3D7, and the result revealed that only the compound 2 containing a valine linker was tolerated. Another round of lead optimization focused on the replacement of the m-anisidine moiety in compound 2. A library of 12 derivatives was prepared, and the antimalarial assay showed that potent antimalarial activity could be maintained by replacing the methoxy group in the meta position of the phenyl side chain with a fluorine or chlorine atom (21: IC50 = 36 ± 5 nM, 24: IC50 = 22 ± 5 nM). Further lead optimization is underway to enhance the antimalarial activity of this class of compound. The compounds included in the study possess little to no antiproliferative activity against MCF-7 cells.

ISOLATION, CHARACTERIZATION AND EVALUATION FOR ANTIPLASMODIAL ACTIVITY OF EXTRACTED CONSTITUENTS FROM CAESALPINIA CRISTA LINN SEEDS

The present work deals with extraction, isolation and characterization of phytoconstituents from seeds of Caesalpinia crista Linn and the study of their antiplasmodial activity. The phytoconstituents were extracted using soxhlet apparatus and separated by column chromatography. Structural elucidation was done by FTIR spectroscopy, NMR spectroscopy and mass spectrometry. Terpenoid, saponin and steroidal glucocorticoid were successfully isolated and identified. These constituents were tested for antimalarial activity using Peter’s 4 day suppressive test. Antiplasmodial efficacy was evaluated by parasitemia levels, percentage inhibition, packed cell volume (PCV), survival period, body weight and rectal temperature change. From the ethyl acetate extract, the fractions obtained with a solvent system hexane:chloroform (4:6 v/v), hexane:chloroform (1:9 v/v) and chloroform:ethyl acetate (6:4 v/v) exhibited promising antimalarial activity and particularly first constituent showed significant (P&lt;0.001) antiplasmodial activity than other two phytoconstituents in comparison with positive and negative control.

Therapeutic Potency of Mono- and Diprenylated Acetophenones: A Case Study of In-Vivo Antimalarial Evaluation

AbstractMalaria remains a febrile infection of public health concern in many countries especially tropical countries in Africa and certain countries in Southern and North America such as Brazil, Costa Rica, Mexico, Dominican Republic, Colombia, and Ecuador. Hence this has made research into this area paramount. Acetophenones are active fragments in many compounds with promising antimalarial activity, such as chalcones. The aim of the present study was to investigate antimalarial activity of 3,5-diprenyl acetophenone (I) and 5-diprenyl acetophenone (II) in in vivo. In this study, compounds I and II were synthesized using an aromatic substitution reaction. The in-vivo antimalarial potential of compounds I and II was analyzed in Plasmodium berghei-infected mice. Our data showed that compound I (25, 50, and 100 mg/kg) had promising antimalarial activity, with parasitemia inhibited rate being 68.03, 65.16, and 69.75%, respectively. Compound II dose-dependently inhibited parasitemia levels, it demonstrated an infinitesimally higher activity (72.12%) when compared with compound I (69.75%) at 100 mg/kg dose. The two compounds passed the rule of three, Lipinski's rule of five, predicted plausible pharmacokinetic profile (ADME), and apparent safety profile, and demonstrated drug-like fragments. The study provided guidance in exploring novel antimalarial compounds based on the scaffolds of prenylated acetophenones.

Antimalarial efficacy and toxicological assessment of medicinal plant ingredients of Prabchompoothaweep remedy as a candidate for antimalarial drug development

BackgroundDrug resistance exists in almost all antimalarial drugs currently in use, leading to an urgent need to identify new antimalarial drugs. Medicinal plant use is an alternative approach to antimalarial chemotherapy. This study aimed to explore potent medicinal plants from Prabchompoothaweep remedy for antimalarial drug development.MethodsForty-eight crude extracts from Prabchompoothaweep remedy and its 23 plants ingredients were investigated in vitro for antimalarial properties using Plasmodium lactate dehydrogenase (pLDH) enzyme against Plasmodium falciparum K1 strain and toxicity effects were evaluated in Vero cells. The plant with promising antimalarial activity was further investigated using gas chromatography-mass spectrometry (GC-MS) to identify phytochemicals. Antimalarial activity in mice was evaluated using a four-day suppressive test against Plasmodium berghei ANKA at dose of 200, 400, and 600 mg/kg body weight, and acute toxicity was analyzed.ResultsOf the 48 crude extracts, 13 (27.08%) showed high antimalarial activity against the K1 strain of P. falciparum (IC50 < 10 μg/ml) and 9 extracts (18.75%) were moderately active (IC50 = 11–50 μg/ml). Additionally, the ethanolic extract of Prabchompoothaweep remedy showed moderate antimalarial activity against the K1 strain of P. falciparum (IC50 = 14.13 μg/ml). Based on in vitro antimalarial and toxicity results, antimalarial activity of the aqueous fruit extract of Terminalia arjuna (IC50 = 4.05 μg/ml and CC50 = 219.6 μg/ml) was further studied in mice. GC-MS analysis of T. arjuna extract identified 22 compounds. The most abundant compounds were pyrogallol, gallic acid, shikimic acid, oleamide, 5-hydroxymethylfurfural, 1,1-diethoxy-ethane, quinic acid, and furfural. Analysis of the four-day suppressive test indicated that T. arjuna extract at dose of 200, 400, and 600 mg/kg body weight significantly suppressed the Plasmodium parasites by 28.33, 45.77, and 67.95%, respectively. In the acute toxicity study, T. arjuna extract was non-toxic at 2000 mg/kg body weight.ConclusionsThe aqueous fruit extract of T. arjuna exerts antimalarial activity against Plasmodium parasites found in humans (P. falciparum K1) and mice (P. berghei ANKA). Acute toxicity studies showed that T. arjuna extract did not show any lethality or adverse effects up to a dose of 2000 mg/kg.

SYNTHESIS AND ANTIMALARIAL EVALUATION OF 1-(2,4- DIMETHOXYPHENYL)-3-(4-TRIFLUORO METHYL-PHENYL) PROPAN-2-ENE-1- ONE

Malaria is one of the most serious health problems worldwide and Its treatment has been compromised by drug resistance. Chalcones represent an important chemical scaffold with promising antimalarial activity. A chalcone derivative; 1(2,4dimethoxyphenyl)-3-(4-trifluoro methyl-phenyl) propan-2-ene-1-one (Compound P21) was synthesized by modified ClaisenSchmidt condensation reaction. The structure of compound P21 was established using Fourier transform infrared (FT-IR), proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, and also mass spectrometry (MS). The compound was screened for in-vivo antimalarial activity in mice infected with P berghii parasite, using curative model. Compound P21 displayed appreciable activity (66% parasitaemia suppression) comparable to that of chloroquine (5 mg kg-1) at a dose of 175mg kg-1 in the curative test (p&lt;0.05). The present finding suggests that compound P21 is a promising antimalarial compound and is a candidate for further optimization and evaluation.

Synthesis, antimalarial, antileishmanial evaluation, and molecular docking study of some 3-aryl-2-styryl substituted-4(3H)-quinazolinone derivatives

Quinazolinones are a diverse group of nitrogen-containing heterocyclic compounds with promising antimalarial and antileishmanial activities. Herein, some 3-aryl-2-styryl substituted-4(3H)-quinazolinones were synthesized via cyclization, condensation, and hydrolysis reactions. 1H NMR, FTIR and elemental microanalysis was used to verify the structures of the synthesized compounds. The in vivo antimalarial and in vitro antileishmanial activities of the target compounds were investigated using mice infected with Plasmodium berghi ANKA and Leishmania donovani strain, respectively. Among the test compounds, 8 and 10 showed better antimalarial activities with percent suppression of 70.01 and 74.18, respectively. In addition, (E)-2-(4-nitrostyryl)-3-phenylquinazolin-4(3H)-one (6) showed promising antileishmanial activity (IC50 = 0.0212 µg/mL). It is two and 150 times more active than the standard drugs amphotericin B deoxycholate (IC50 = 0.0460 µg/mL) and miltefosine (IC 50 = 3.1911 µg/mL), respectively. Its superior in vitro antileishmanial activity was supported by a molecular docking study conducted in the active site of Lm-PTR1. Overall, the synthesized 3-aryl-2-styryl substituted-4(3H)-quinazolinones showed promising antileishmanial and antimalarial activities and are desirable scaffolds for the synthesis of different antileishmanial and antimalarial agents.

Antimalarial activity of the hydroalcoholic crude extract and solvent fractions of Commelina latifolia Hochst. ex C.B.Clarke (Commelinaceae) leaves against Plasmodium berghei in mice

Ethnopharmacological relevanceIn Ethiopia, the indigenous medicinal plant Commelina latifolia Hochst. ex C.B. Clarke leaves are used to treat malaria and wounds. Aim of the studyIn this work, the antiplasmodial activity of Commelina latifolia crude leaf extract and solvent fractions against Plasmodium berghei-infected mice was investigated. Materials and methods80% methanol was used to extract the leaves of C. latifolia, and the crude extract was fractionated using chloroform, pure methanol, and distilled water. All test compounds were undergone an acute oral toxicity test before being put through Peter’s 4-day suppressive test to see if they have antiplasmodial activity. The hydroalcoholic crude extract and chloroform fraction were additionally assessed for antimalarial activity using curative and prophylactic tests in P. berghei-infected laboratory mice. ResultsAll of the tested crude extracts were safe at a dose of 2000 mg/kg. At 400 mg/kg dose both the 80% methanol extract and chloroform fraction exhibited antimalarial activity with parasitemia suppression values of 86.31%, and 76.56% in the four-day suppressive test, 81.97% and 72.05% in Rane's test, and 69.05% and 62.88% in the prophylactic test, respectively. ConclusionCollectively, the oral dose of Commelina latifolia is safe, and reveals promising antimalarial activity. The findings backed up the utilization of the plant in traditional medicine to treat malaria.

Studying the Rationale of Fire Ant Sting Therapy Usage by the Tribal Natives of Bastar Revealed Ant Venom-Derived Peptides with Promising Anti-Malarial Activity.

Prevailing drug resistance in malaria imposes the major roadblock for the existing interventions necessitating the timely need to search for alternative therapies. Ants in Solenopsis spp, termed 'Fire ants', are well known for their aggressive behavior, which leads to the release of toxic venom. Notably, the tribal natives of the malaria-laden densely forested Bastar region, Chhattisgarh, India, use fire ant sting-based therapy to cure malaria-like high fever. Inspired by this, we have collected the fire ants from the forest of Bastar and extracted peptide and alkaloid fractions from ant venom using HPLC and analyzed them by LC/MS-based applications. Evaluation of the anti-malarial efficacy of these peptide fractions demonstrated a significant reduction in the growth of Plasmodium falciparum (Pf 3D7) in vitro, whereas the alkaloid fraction showed a negligible effect. in vitro hemolytic activity confirmed the venom peptide fraction to be non-hemolytic. Additionally, the venom peptide fraction is purely non-toxic to HepG2 cells. Anti-malarial efficiency of the same in Plasmodium berghei ANKA infected mice models showed a drastic reduction in parasitemia representing promising anti-malarial activity. Overall, our study has unraveled the scientific rationale underlying fire ant sting therapy used as a tribal naturotherapy for curing malaria-like fever, thus, introducing a way forward to develop nature-inspired anti-malarial chemotherapeutics.

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 &gt;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.