3D7 Strain Research Articles

Gene expression levels and inhibitory effect of 7-[(7-methoxy-4,5-dihydro-1H-benzo[g]indazol-3-yl)carbonyl]-2-phenyl-5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]Pyrimidin-9(1H)-one (MCL) against AP2-I and BDP1 in malaria experimental models

Resistance to antimalarial drugs leads a global recurrence of malaria, posing a significant challenge to malaria control. This study aimed to assess gene expression and resistance profiles in clinical isolates, and validate the inhibitory effect of MCL compound against PbAP2-I and PbBDP1 genes in vivo. Malaria prevalence rate throughout the clinical study period stood at 12.24%. Blood samples were obtained from 182 malaria outpatients and 30 P. berghei-infected mice treated with varying MCL concentrations. DNA and RNA were extracted. PfAP2-I, PfBDP1, PfMDR1, and PfK13 genes were amplified using Real-time qPCR and sequenced for mutation profiling. Relative gene expression of AP2-I and BDP1 genes in P. falciparum and P. berghei-treated mice was carried out by Reverse-transcription PCR. The data were analyzed using ANOVA at P<0.05 indicating a significant difference. Relative gene expression results from clinical isolates showed PfAP2-I and PfBDP1 are highly expressed in the trophozoite and schizont stages. The clinical isolates show conserved nucleotide sequences for PfAP2-I, PfBDP1, and PfK13 genes compared to the 3D7 strain. However, Asn86Tyr mutation implicated in antimalarial drug resistance and Leu1312Iso mutation not previously reported to be associated with antimalarial drug resistance were observed for the PfMDR1 gene. MCL inhibited the expression of PbAP2-I (by 4.52 and 8.08 folds) and PbBDP1 (by 37.92 and 79.07 folds) at 40µM and 50µM concentrations after a 7-day, single oral daily dose. Our findings validate MCL's inhibitory activity against AP2-I and BDP1 genes, hence representing potential new targets of antimalarial therapy for controlling malaria parasite invasion.

Phenolic-rich extracts from toasted white and tannin sorghum flours have distinct profiles influencing their antioxidant, antiproliferative, anti-adhesive, anti-invasive, and antimalarial activities

Sorghum is a gluten-free cereal commonly used in foods, and its consumption has been associated with the prevention of human chronic conditions such as obesity and cancer, due to the presence of dietary fiber and phenolic compounds. This study aimed to evaluate, for the first time, the antiproliferative, antioxidant, anti-adhesion, anti-invasion, and antimalarial activities of phenolic extracts from toasted white and tannin sorghum flours to understand how different phenolic profiles contribute to sorghum biological activities. Water and 70 % ethanol/water (v/v), eco-friendly solvents, were used to obtain the phenolic extracts of toasted sorghum flours, and their phenolic profile was analyzed by UPLC-MSE. One hundred forty-five (145) phenolic compounds were identified, with 23 compounds common to all extracts. The solvent type affected the phenolic composition, with aqueous extract of both white sorghum (WSA) and tannin sorghum (TSA) containing mainly phenolic acids. White sorghum (WSE) and tannin sorghum (TSE) ethanolic extracts exhibited a higher abundance of flavonoids. WSE demonstrated the lowest IC50 on EA.hy926 (IC50 = 46.6 µg/mL) and A549 cancer cells (IC50 = 33.1 µg/mL), while TSE showed the lowest IC50 (IC50 = 70.8 µg/mL) on HCT-8 cells (human colon carcinoma). Aqueous extracts also demonstrated interesting results, similar to TSE, showing selectivity for cancer cells at higher IC50 concentrations. All sorghum extracts also reduced the adhesion and invasion of HCT-8 cells, suggesting antimetastatic potential. WSE, rich in phenolic acids and flavonoids, exhibited greater toxicity to both the W2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains of Plasmodium falciparum (IC50 = 8 µg GAE/mL and 22.9 µg GAE/mL, respectively). These findings underscore the potential health benefits of toasted sorghum flours, suggesting diverse applications in the food industry as a functional ingredient or even as an antioxidant supplement. Moreover, it is suggested that, besides the phenolic concentration, the phenolic profile is important to understand the health benefits of sorghum flours.

Synthesis, Activity Test and Molecular Docking of Novel Nitrophenylcalix[4]-2-methylresorcinarene Derivatives as Antimalarial Agent

This research involved the synthesis, antimalarial assay and molecular docking of novel nitrophenylcalix[4]-2-methylresorcinarene derivatives. Calix[4]-2-methylresorcinarene derivatives, i.e., 2N, 3N and 4N, were synthesized in a one-step reaction through the cyclo-condensation reaction between resorcinol and aldehydes, i.e., 2-nitrobenzaldehyde, 3-nitrobenzaldehyde and 4-nitrobenzaldehyde, respectively. The reaction was carried out through the reflux method with ethanol and hydrochloric acid 37% as the solvent and catalyst, respectively. The synthetic products were characterized using FTIR, 1H-NMR, 13C-NMR, and LC-MS spectrometers. Furthermore, the in vitro antimalarial assay was carried out against Plasmodium falciparum strain 3D7. The results showed that the 2N, 3N and 4N compounds were successfully synthesized in 86.4, 78.6 dan 95.7% yield, respectively. The antimalarial activity test of 2N, 3N and 4N gave IC50 values of 2.35, 1.68 and 1.79 µM, therefore, these compounds are classified as active antimalarial agents. Molecular docking performed against the PfLDH receptor showed that the 2N, 3N and 4N compounds had negative binding affinity values of -5.1, -6.1, and -6.0 kcal/mol and had specific interactions in the form of hydrogen bonds to the amino acid residues Arg109, Thr101 and Lys102 in the active site of the receptor. The molecular docking results agreed with the experimental antimalarial assay demonstrating the mechanism of action of nitrophenylcalix[4]-2-methylresorcinarenes as active antimalarial agents happened through the inhibition of the PfLDH receptor.

In vitro drug interaction of ionophores with artemisinin and chloroquine against Plasmodium falciparum 3D7 blood-stage infection

The prevalence of clinical resistance of P. falciparum towards artemisinin and its partner drugs has significantly hampered malarial chemotherapy. To circumvent this situation, identifying a new class of partner drugs with significant anti-malarial efficacy and multi-stage activity can slow the development of resistance. This study demonstrates the potential interactions of carboxylic ionophores such as monensin (MON), maduramicin (MAD) or salinomycin (SAL) with standard antimalarial drugs artemisinin (ART) or chloroquine (CQ). The in vitro drug interactions were studied in P. falciparum 3D7 strain by a growth inhibition SYBR green 1 assay. The asynchronized parasites were exposed for 48 h in the presence of varying proportions of two drug concentrations using the modified fixed-ratio isobologram method. We determined the growth inhibition response and the sums of the fractional inhibitory concentrations (ΣFICs) of the following drug combinations (4:1, 3:2, 2:3, 1:4) and (1:1, 1:3, 3:1) were calculated for 50% inhibitory concentrations (IC50s). Combining artemisinin with monensin, maduramicin, or salinomycin showed significant additive interaction. A combination of chloroquine with monensin, maduramicin, or salinomycin showed slight synergism to additive interaction. None of the drug combinations displayed an antagonistic effect indicating ionophores usage in combination therapy to treat drug-resistant malarial infections.

Synthesis of chalcone derivatives with methoxybenzene and pyridine moieties as potential antimalarial agents

Malaria remains an endemic disease in tropical regions, urgently needed the search for effective antimalarial agents due to resistance against existing drugs. This study investigated the potential antimalarial activity of pyridine-based chalcone derivatives against P. falciparum 3D7 and FCR3 strains. The chalcones were synthesized through a one-pot method using various pyridine carbaldehyde, resulting in yields ranging from 53.74 to 86.37%, and all products were characterized using FTIR, GC-MS, and NMR spectroscopies. Among the six chalcones tested, chalcone A [1-(2-methoxyphenyl)-3-(pyridin-2-yl)prop-2-en-1-one] displayed the highest antimalarial activity with IC50 values of 0.48 and 0.31 μg/mL against P. falciparum 3D7 and FCR3 strains, respectively, and a resistance index of 0.65. Molecular docking studies highlighted the interaction of the carbonyl group of all chalcones with Asn108 amino acid residue in the PfDHFR-TS active site via hydrogen bonding, demonstrating their potential as the antimalarial agent. Notably, the positioning of methoxy and pyridine substituents significantly influenced the antimalarial activity of the chalcones.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21β-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21β-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 μg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 μg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 μg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 μg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21β-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21β-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

Heterotrophic nitrifying bacteria from activated sludge in DHS reactor for ammonium removal of natural rubber processing wastewater treatment

Two heterotrophic nitrifying bacterial strains, D2 and D7 were isolated from an activated sludge of sponges in a laboratory-scale downflow hanging sponge reactor. Both strains exhibited efficient ammonium removal ability over a wide range of ammonium loads. At the initial concentration of 100 mg/L, NH4+-N was completely degraded within 20 h by both strains. When the initial concentration was increased to 200 mg/L, the NH4+-N removal efficiency was 99.6 % within 20 h by the strain D2 and 61.3 % by the strain D7. In natural rubber processing wastewater, the ammonium removal efficiencies of strain D2 and D7 were 38 % and 99 % with the initial N-NH4+ concentration of 280 and 380 mg/L after 88 h, respectively. The 16S rRNA gene sequence of D2 and D7 showed the highest similarity to the Pseudomonas aeruginosa and Glutamicibacter nicotianae, respectively. This is the first report to demonstrate the ability to remove ammonium in NRPW by ​heterotrophic nitrifying bacteria isolated from activated sludge in DHS reactor.

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.

Hybrid PABA-glutamic acid conjugated 1,3,5-triazine derivatives: Design, synthesis, and antimalarial activity screening targeting Plasmodium falciparum dihydro folate reductase enzyme.

Despite the successful reduction in the malaria health burden in recent years, it continues to remain a significant global health problem mainly because of the emerging resistance to first-line treatments. Also because of the disruption in malaria prevention services during the COVID-19 pandemic, there was an increase in malaria cases in 2021 compared to 2020. Hence, the present study outlined the in silico study, synthesis, and antimalarial evaluation of 1,3,5-triazine hybrids conjugated with PABA-glutamic acid. Docking study revealed higher binding energy compared to the originally bound ligand WR99210, predominant hydrogen bond interaction, and involvement of key amino acid residues, like Arg122, Ser120, and Arg59. Fourteen compounds were synthesized using traditional and microwave synthesis. The in vitro antimalarial evaluation against chloroquine-sensitive 3D7 and resistant Dd2 strain of Plasmodium falciparum showed a high to moderate activity range. Compounds C1 and B4 showed high efficacy against both strains and a further study revealed that compound C1 is non-cytotoxic against the HEK293 cell line with no acute oral toxicity. In vivo, study was performed for the most potent antimalarial compound C1 to optimize the research work and found to be effectively suppressing parasitemia of Plasmodium berghei strain in the Swiss albino mice model.

Lupane derivatives: Design, isolation, synthesis and evaluation of antiplasmodial activity against Plasmodium falciparum 3D7 strain

Lupane derivatives: Design, isolation, synthesis and evaluation of antiplasmodial activity against Plasmodium falciparum 3D7 strain

Comparison of SYBR green I and lactate dehydrogenase antimalarial in vitro assay in Plasmodium falciparum field isolates

Several assay methods are in use for monitoring the drug sensitivity of malaria parasites and screening new antimalarial drugs. Plasmodium lactate dehydrogenase (pLDH) and SYBR Green I in vitro assays were used to evaluate the drug efficacy of Chloroquine, Artemisinin and Azadirachta indica silver nano particles against Plasmodium falciparum 3D7 strain. The half-maximal inhibitory concentration (IC50) of each compound was estimated with non-linear regression model – dose-response analysis. The consistency between two methods was analysed with Cohen's kappa coefficient, interclass correlation and Bland-Altman plots. No statistical difference was found between IC50 values determined by both assays (p = 0.714). The proportion of resistant isolates to chloroquine according to SYBR green I (43.48%) and pLDH (34.78%) assays were similar (z = 0.302; p = 0.762) with significant concordant between methods (k = 0.819, p < 0.001). The results of pLDH Qualisa assay was comparable with classic SYBR green I assay and can be potentially useful in antimalarial drug efficacy surveillance.

Ceramicines U-Z from Chisocheton ceramicus and structure-antimalarial activity relationship study.

Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a β-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2µM. In addition, the structure-antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.

Geo-environmental factors and the effectiveness of mulberry leaf extract in managing malaria

Malaria prevalence has become medically important and a socioeconomic impediment for the endemic regions, including Purulia, West Bengal. Geo-environmental variables, humidity, altitude, and land use patterns are responsible for malaria. For surveillance of the endemic nature of Purulia’s blocks, statistical and spatiotemporal factors analysis have been done here. Also, a novel approach for the Pf malaria treatment using methanolic leaf extract of Morus alba S1 has significantly reduced the parasite load. The EC50 value (1.852) of the methanolic extract of M. alba S1 with P. falciparum 3D7 strain is close to the EC50 value (0.998) of the standard drug chloroquine with the same chloroquine-sensitive strain. Further studies with an in-silico model have shown successful interaction between DHFR and the phytochemicals. Both 1-octadecyne and oxirane interacted favourably, which was depicted through GC–MS analysis. The predicted binary logistic regression model will help the policy makers for epidemiological surveillance in malaria-prone areas worldwide when substantial climate variables create a circumstance favourable for malaria. From the in vitro and in silico studies, it can be concluded that the methanolic extract of M. alba S1 leaves were proven to have promising antiplasmodial activity. Thus, there is a scope for policy-driven approach for discovering and developing these lead compounds and undermining the rising resistance to the frontline anti-malarial drugs in the world.

Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity.

In tropical and subtropical areas, malaria stands as a profound public health challenge, causing an estimated 247 million cases worldwide annually. Given the absence of a viable vaccine, the timely and effective treatment of malaria remains a critical priority. However, the growing resistance of parasites to currently utilized drugs underscores the critical need for the identification of new antimalarial therapies. Here, we aimed to identify potential new drug candidates against Plasmodium falciparum, the main causative agent of malaria, by analyzing the transcriptomes of different life stages of the parasite and identifying highly expressed genes. We searched for genes that were expressed in all stages of the parasite's life cycle, including the asexual blood stage, gametocyte stage, liver stage, and sexual stages in the insect vector, using transcriptomics data from publicly available databases. From this analysis, we found 674 overlapping genes, including 409 essential ones. By searching through drug target databases, we discovered 70 potential drug targets and 75 associated bioactive compounds. We sought to expand this analysis to similar compounds to known drugs. So, we found a list of 1557 similar compounds, which we predicted as actives and inactives using previously developed machine learning models against five life stages of Plasmodium spp. From this analysis, two compounds were selected, and the reactions were experimentally evaluated. The compounds HSP-990 and silvestrol aglycone showed potent inhibitory activity at nanomolar concentrations against the P. falciparum 3D7 strain asexual blood stage. Moreover, silvestrol aglycone exhibited low cytotoxicity in mammalian cells, transmission-blocking potential, and inhibitory activity comparable to those of established antimalarials. These findings warrant further investigation of silvestrol aglycone as a potential dual-acting antimalarial and transmission-blocking candidate for malaria control.

Evaluating phytochemical constituents and in-vitro antiplasmodial and antioxidant activities of Fadogiella stigmatoloba, Hygrophylla auriculata, Hylodesmum repandum, and Porphyrostemma chevalieri extracts

IntroductionFadogiella stigmatoloba, Hygrophylla auriculata, Hylodesmum repandum and Porphyrostemma chevalieri are used against malaria in traditional medicine in the Democratic Republic of the Congo (DRC). To evaluate their potential in the treatment of this disease, the in vitro antiplasmodial property of these four plants was evaluated. All experiments were conducted on methanolic extracts performed on selected organ parts of these plants. MethodsThe methanolic extracts, obtained by maceration, were firstly screened in vitro against the chloroquine sensitive (3D7) and resistant (W2) Plasmodium falciparum strains by the measurement of lactate dehydrogenase activity, and on human keratinocytes (HaCat) cells by the MTT assay to determine their selectivity indices (SI). Secondly, the antioxidant activity of the same extracts was evaluated using DPPH and FRAP assays. Finally, the presence of specific phytochemical constituents was evaluated using standard methods and tentatively identified by GC-MS. ResultsAn optimum antiplasmodial activity (IC50 = 3.4 ± 0.7 μg/mL, for 3D7, SI = 58.2; IC50 = 7 ± 1.0 μg/mL, for W2, SI = 28.3) was obtained with the leave extract of P. chevalieri. The leaves (for F. stigmatoloba and H. repandum), and the aerial part (for H. repandum) extracts showed promising and moderate antiplasmodial activities against respectively the 3D7 strain (IC50: <15 μg/mL), and W2 strain (IC50:15–50 μg/mL). All extracts presented a weak cytotoxic effect (IC50: >100 μg/mL) on HaCat cells. For the antioxidant test, the most interesting activity was obtained with the leaf extract of P. chevalieri. The GC–MS analysis of these four plants species extracts revealed the presence of various compounds, such as Ethyl 2-nonenoate, 2-(2-Hydroxy-2-phenylethyl)-3,5,6-trimethyl pyrazine, Palmitic Acid, Ethyl palmitate, Ethyl linolenate, and N-Acetyltyramine. ConclusionBased on the obtained results, P. chevalieri could be selected for further investigations or ⁄and for the management of malaria after standardization.

Synthesis and antimalarial activity of novel 3-substituted chloroquine derivatives

The synthesis and characterization of a series of new 3-substituted chloroquine (CQ) derivatives are reported along with their antimalarial activity against CQ-sensitive, 3D7, and CQ-resistant, Dd2, strains of Plasmodium falciparum. The new CQ derivatives stem from the aroylation of 3-aminochloroquine, which in turn is prepared in four efficient steps from 4,7-dichloroquinoline. Variation of the aroylation substituents and ring substitution patterns reveal that 4-substitution with electron-withdrawing moieties results in the lowest IC50 values, both in the same order of magnitude as CQ itself for the 3D7 strain. Given its activity against the resistant Dd2 strain, the 4-chlorobenzamido-CQ derivative is chosen as the lead compound for potential use in combination therapy.

Evaluation of in vitro antiplasmodial, antiproliferative activities, and in vivo oral acute toxicity of Spathodea campanulata flowers

Spathodea campanulata is used in traditional medicine to treat various ailments such as malaria, human immunodeficiency virus (HIV), cancer, fever and urethral inflammation. The aim of this study was to investigate the antiplasmodial, and antiproliferative activities of the extract and resulted fractions from S. campanulata flowers, as well as assessing the acute toxicity of its aqueous fraction. The in vitro cell-growth inhibition activities were assessed against Plasmodium falciparum strain 3D7 for antimalarial activity and three cancer cell lines: Hs683 (human oligodendroglioma), MCF7 (human breast carcinoma), and murine B16F10 (mouse melanoma) for antiproliferative activity while the in vivo acute oral toxicity was determined according to the modified organisation for Economic Co-operation and Development (OECD) guidelines 423 at a fixed dose on Female Wistar strain laboratory rats. The dichloromethane, ethyl acetate and hexane fractions at a concentration of 25 µg/mL each significantly reduced the viability of 3D7 Plasmodium cells with viability percentages of 19.0%, 14.1% and 31.9%, respectively, and IC50 of 28.1, 30.2 and 29.7 µg/mL, respectively. The ethyl acetate fraction showed a moderate antiproliferative activity on mouse melanoma with an I50 value of 54.6 µg/mL. Only the dichloromethane fraction was able to inhibit the 3 cell lines tested with IC50 values less than 15 µg/mL. An oral administration of the aqueous fraction did not induce an abnormal variation of the physiological parameters in female Wistar laboratory rats, at non-toxic doses up to 5000 mg/kg body weight for 14 days. These results confirm the use of this plant in traditional medicine for its antimalarial and anticancer potential.

Synthesis and Antimalarial Evaluation of New 1,3,5-tris[(4-(Substituted-aminomethyl)phenyl)methyl]benzene Derivatives: A Novel Alternative Antiparasitic Scaffold

A series of new 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds were designed, synthesized, and evaluated in vitro against two parasites (Plasmodium falciparum and Leishmania donovani). The biological results showed antimalarial activity with IC50 values in the sub and μM range. The in vitro cytotoxicity of these new aza polyaromatic derivatives was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene 1m was found as one of the most potent and promising antimalarial candidates with a ratio of cytotoxic to antiprotozoal activities of 83.67 against the P. falciparum CQ-sensitive strain 3D7. In addition, derivative 1r was also identified as the most interesting antimalarial compound with a selectivity index (SI) of 17.28 on the W2 P. falciparum CQ-resistant strain. It was previously described that the telomeres of P. falciparum could be considered as potential targets of these kinds of aza heterocycles; thus, the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes was measured through a FRET melting assay.

Ex vivo and in vitro antiplasmodial activity and toxicity of Caesalpinia decapetala (Roth) Alston (Fabaceae)

Ethnopharmacological relevanceMalaria is among the most prevalent and devastating parasitic diseases globally with most cases reported in Sub-Saharan Africa. One of the major reasons for the high malaria prevalence is the ever-increasing emergence of resistant strains of malaria-causing parasites to the currently used antimalarial drugs. This, therefore, calls for the search for antimalarial compounds with alternative modes of action. Plants used in traditional medicine for the treatment of malaria offer possible sources of such compounds. Caesalpinia decapetala has been used traditionally for the treatment of various diseases including malaria. However, the antiplasmodial activity of the plant has never been reported. Aim of the studyTo determine the ex vivo and in vitro antiplasmodial activities of the extracts of the roots, stem bark and leaves of Caesalpinia decapetala. MethodologyThe roots, stem bark and leaves of Caesalpinia decapetala (Roth) Alston (Caesalpiniaceae) were collected and air-dried under a shade then extracted consecutively with dichloromethane and methanol (1:1 (v/v) (4 × 0.8 L). The extracts were tested for antiplasmodial activities against four strains of Plasmodium falciparum (W2, DD2, 3D7, and D6) and fresh P. falciparum field isolates using the SYBR green I assay. The mean fifty percent inhibition concentration (IC50) was determined for each assay. An acute oral toxicity test was done based on the Organization for Economic Cooperation and Development (OECD 425) guidelines using Swiss albino mice. ResultsThe leaves and stem bark extracts showed good antiplasmodial activities with IC50 values of 4.54 and 4.86 μg/mL, respectively, when tested against the fresh field isolates ex vivo. Similarly, the roots extract showed an IC50 value of 6.49 μg/mL when tested against field isolates ex vivo. The roots extract showed the highest antiplasmodial activities among the samples when tested against W2 (IC50 = 6.12 μg/mL), DD2 (IC50 = 8.17 μg/mL), and D6 (IC50 = 16.02 μg/mL) strains of P. falciparum whereas the leaves showed the highest activity (IC50 = 9.3 μg/mL) when tested against the 3D7 strain of P. falciparum. No mortality was observed for the mice treated with 2000 mg/kg of the leaves and stem bark extracts. The mouse treated with 2000 mg/kg of the roots extracts regained weight by day 12 of the observation period. ConclusionCaesalpinia decapetala has the potential to suppress the growth of P. falciparum thereby contributing to combating the recurrent emergence of antimalarial drug resistance.