Multidrug-resistant K1 Strain Research Articles

Evaluation of 4-Aminoquinoline Hydrazone Analogues as Potential Leads for Drug-Resistant Malaria.

The emergence of resistance to first-line antimalarial drugs calls for the development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on the multidrug-resistant K1 strain of Plasmodium falciparum: IC50 values after a 48 h cycle ranged from 0.60 to 49 µM, while the 72 h cycle ranged from 0.026 to 0.219 μM. Time-course assays were carried out to define the activity of the lead compounds, which inhibited over 50% growth in 24 h and 90% growth in 72 h. Cytotoxicity assays with HepG2 cells showed IC50 values of 0.87-11.1 μM, whereas in MDBK cells, IC50 values ranged from 1.66 to 11.7 μM. High selectivity indices were observed for the lead compounds screened at 72 h on P. falciparum. Analyses of stage specificity revealed that the ring stages of the parasite life cycle were most affected. Based on antimalarial efficacy and in vitro safety profiles, lead compound 4-(2-benzylidenehydrazinyl)-6-methoxy-2-methylquinoline 2 was progressed to drug combination studies for the detection of synergism, with a combinatory index of 0.599 at IC90 for the combination with artemether, indicating a synergistic antimalarial activity. Compound 2 was screened on different strains of P. falciparum (3D7, Dd2), which maintained similar activity to K1, suggesting no cross-resistance between multidrug resistance and sensitive parasite strains. In vivo analysis with 2 showed the suppression of parasitaemia with P. yoelii NL (non-lethal)-treated mice (20 mg/kg and 5 mg/kg).

Bioassay-Guided Isolation and Identification of Antiplasmodial Compounds from the Stem Bark of Clausena excavata.

Clausena excavata is a medicinal plant widely distributed in Southeast Asia. It is used for a variety of indications, including to treat malaria. In our present study, a phytochemical study of the methanol extract from the stem bark of C. excavata led to the isolation of five pyranocoumarins, nordentatin (1: ), dentatin (2: ), kinocoumarin (3: ), clausarin (4: ), and clausenidin (5: ), and a coumarin, 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol (6: ). The isolation of compound 6: from C. excavata and the antiplasmodial activities against a multidrug-resistant K1 strain of Plasmodium falciparum of 1, 3: , and 5: were reported for the first time. Compounds 3: and 4: exhibited potent antiplasmodial activities with EC50 values of 1.10 and 0.58 µM, respectively, while 1: and 5: had EC50 values of 5.62 and 7.15 µM, respectively. A prenyl group attached to the C-3 or C-12 position on the pyranocoumarin ring probably plays an important role on the activity. A hydroxyl group at the C-10 position is also likely to enhance the activity.

First Total Syntheses of Natural Phenanthrene Alkaloids, Uvariopsamine, Noruvariopsamine, 8-Hydroxystephenanthrine, 8-Methoxyuvariopsine, Thalihazine, and Secophoebine, and Their Potential as Antimalarial Agents.

The first total syntheses of natural phenanthrene alkaloids, namely, uvariopsamine (1), noruvariopsamine (2), 8-hydroxystephenanthrine (3), 8-methoxyuvariopsine (4), thalihazine (5), and secophoebine (6), have been realized. In addition, their in vitro antimalarial activity against the multidrug-resistant K1 strain of Plasmodium falciparum and in vitro cytotoxic activity against the human nasopharynx carcinoma (KB), small cell lung cancer (NCI-H187), and breast cancer (MCF7) human cancer cell lines were investigated. All the phenanthrene alkaloids showed significant antiplasmodial activity (IC50 1.07-7.41 µM), and most compounds displayed low to no toxicity against the three cancer cell lines tested. Particularly, 3 exhibited the best antimalarial activity with an IC50 value of 1.07 µM, no toxicity to NCI-H187 (IC50 > 50 µM), and low toxicity against KB (IC50 24.53 µM) and MCF7 (IC50 42.67 µM) cell lines.

Crude Ethanolic Stem Bark Extract of Zanthoxylum zanthoxyloides and Its Fractions: In-Vitro and In-Vivo Antiplasmodial Activity

Malaria is a global problem, as treatment failure has hampered the efficacy of most anti-malarial medications. The goal of this study was to see if stem bark extract from Zanthoxylum zanthoxyloides had antiplasmodial properties that could be used to treat both susceptible and resistant parasites. The stem bark of Z. zanthoxyloides (500g) was crushed and extracted with ethanol. The extract was tested for antiplasmodial activity in vitro against the chloroquine-sensitive (CQS) strain NF54 and chloroquine-resistant strains (CQR) K1 of P. falciparum, as well as in vivo against the CQS(NK65) strain of P. berghei at 100, 200, and 400 mg/kg bw. Bioassay-guided fractionation of the extract was performed. The crude extract had an in vitro activity of 1076.4 56.4 and 1315.1 121.6 ng/ml against chloroquine sensitive and resistant parasites, respectively while standard drugs (chloroquine and artesunate) were 10.94 nM (3478.92 ng/ml) and 9.24 nM (3215.52ng/ml) for CQS and 310.68 nM (98796 ng/ml) and 10.94 nM (3650.52 ng/ml) for CQR respectively. At Day 7, mice treated with 100, 200, and 400 mg/kg bw crude extract had parasite densities of 1159, 928, and 869 parasites/ µl, respectively (compared to positive control that had 123 parasites /µl). In vitro antiplasmodial activity was best in the K2, K4, and K6 fractions (IC50 were 6670, 6890, and 6480 ng/ml), but in vivo antiplasmodial activity was best in the K4 fraction (1183 parasites/ µl).The stem bark extract of Z. zanthoxyloides have remarkable antiplasmodial activity against both chloroquine sensitive and drug resistant P. falciparum supporting it ethnomedicinal use in malaria treatment.The extract of Z. zanthoxyloides has promising antiplasmodial activity and could be used to generate therapeutic leads against the multidrug-resistant K1 strain of P. falciparum, in addition to providing an alternative allopathic antiplasmodial medication.

Antiplasmodial activity of Anthocleista djalonensis leaves extracts against clinical isolates of Plasmodium falciparum and multidrug resistant K1 strains

Information collected from nine (09) traditional healers in the Moronou village in the Department of Toumodi revealed that Anthocleista djanlonensis is regularly used by the population for primary health care in the processing of malaria. Evaluation of the In vitro antiplasmodial activity showed that the aqueous extracts inhibit growth of clinical isolates and chloroquinoresistant strains (K1) with IC50 of 8.29 µg/mL and 10.23 µg/mL while the ethanolic extracts had IC50 of 37.65 µg/mL and 46.07 µg/mL on the same strains respectively. Results of the In vitro antimalarial bioassay showed that aqueous extracts have promising antiplasmodial effects on clinical isolates and on Plasmodium falciparum multidrug resistant K1 strain (3 µg/mL <IC50 <15 µg/mL). Phytochemical screening revealed that the extracts contain mainly alkaloids, polyphenols, polyterpenes and flavonoids

Antiplasmodial activity of Anthocleista djalonensis leaves extracts against clinical isolates of Plasmodium falciparum and multidrug resistant K1 strains

Antiplasmodial activity of Anthocleista djalonensis leaves extracts against clinical isolates of Plasmodium falciparum and multidrug resistant K1 strains

Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles.

A second generation of 4-aminoquinoline- and 8-aminoquinoline-based tetrazoles and lactams were synthesized via the Staudinger and Ugi multicomponent reactions. These compounds were subsequently evaluated in vitro for their potential antiplasmodium activity against a multidrug-resistant K1 strain and for their antitrypanosomal activity against a cultured T. b. rhodesiense STIB900 strain. Several of these compounds (4a–g) displayed good antiplasmodium activities (IC50 = 0.20–0.62 µM) that were comparable to the reference drugs, while their antitrypanosomal activity was moderate (<20 µM). Compound 4e was 2-fold more active than primaquine and was also the most active (IC50 = 7.01 µM) against T. b. rhodesiense and also exhibited excellent aqueous solubility (>200 µM) at pH 7.

Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and In Vivo Efficacy in the Plasmodium falciparum NSG Mouse Model.

A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure-activity and structure-property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rγnull (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action.

Antimicrobial evaluation of neutral and cationic iridium(III) and rhodium(III) aminoquinoline-benzimidazole hybrid complexes.

A series of neutral and cationic Ir(III) and Rh(III) aminoquinoline-benzimidazole hybrid complexes were synthesised and their inhibitory activities evaluated against Plasmodium falciparum and Mycobacterium tuberculosis. In general, the hybrid complexes display good activity against the chloroquine-sensitive NF54 strain of P. falciparum. The neutral Ir(III)- and Rh(III)-Cp∗ complexes were the most active (IC50=0.488μM for IrIII), maintaining activity against the multidrug-resistant K1 strain. Low to no cytotoxicity against the Chinese hamster ovarian cell line was observed for the tested complexes. Selected active hybrid complexes demonstrated significant inhibition of β-haematin formation in a cell-free NP-40 assay, suggesting an effect on the host haemoglobin degradation pathway as a potential contributing mechanism of action. When tested against M. tuberculosis H37Rv, most hybrid complexes displayed moderate to good activity. Again, the neutral complexes outperformed the cationic complexes, with the neutral Ir(III)-Cp∗ complexes proving most active (MIC90=0.488-1.490μM).

Lerisetron Analogues with Antimalarial Properties: Synthesis, Structure-Activity Relationship Studies, and Biological Assessment.

A phenotypic whole cell high-throughput screen against the asexual blood and liver stages of the malaria parasite identified a benzimidazole chemical series. Among the hits were the antiemetic benzimidazole drug Lerisetron 1 (IC50 NF54 = 0.81 μM) and its methyl-substituted analogue 2 (IC50 NF54 = 0.098 μM). A medicinal chemistry hit to lead effort led to the identification of chloro-substituted analogue 3 with high potency against the drug-sensitive NF54 (IC50 NF54 = 0.062 μM) and multidrug-resistant K1 (IC50 K1 = 0.054 μM) strains of the human malaria parasite Plasmodium falciparum. Compounds 2 and 3 gratifyingly showed in vivo efficacy in both Plasmodium berghei and P. falciparum mouse models of malaria. Cardiotoxicity risk as expressed in strong inhibition of the human ether-a-go-go-related gene (hERG) potassium channel was identified as a major liability to address. This led to the synthesis and biological assessment of around 60 analogues from which several compounds with improved antiplasmodial potency, relative to the lead compound 3, were identified.

Bioisosteric ferrocenyl aminoquinoline-benzimidazole hybrids: Antimicrobial evaluation and mechanistic insights

Phenyl- and bioisosteric ferrocenyl-derived aminoquinoline-benzimidazole hybrid compounds were synthesised and evaluated for their in vitro antiplasmodial activity against the chloroquine-sensitive NF54 and multi-drug resistant K1 strains of the human malaria parasite, Plasmodium falciparum. All compounds were active against the two strains, generally showing enhanced activity in the K1 strain, with resistance indices less than 1. Cytotoxicity studies using Chinese hamster ovarian cells revealed that the hybrids were relatively non-cytotoxic and demonstrated selective killing of the parasite. Based on favourable in vitro antiplasmodial and cytotoxicity data, the most active phenyl (4c) and ferrocenyl (5b) hybrids were tested in vivo against the rodent Plasmodium berghei mouse model. Both compounds caused a reduction in parasitemia relative to the control, with 5c displaying superior activity (92% reduction in parasitemia at 4 × 50 mg/kg oral doses). The most active phenyl and ferrocenyl derivatives showed inhibition of β-haematin formation in a NP-40 detergent-mediated assay, indicating a possible contributing mechanism of antiplasmodial action. The most active ferrocenyl hybrid did not display appreciable reactive oxygen species (ROS) generation in a ROS-induced DNA cleavage gel electrophoresis study. The compounds were also screened for their in vitro activity against Mycobacterium tuberculosis. The hybrids containing a more hydrophobic substituent had enhanced activity (<32.7 μM) compared to those with a less hydrophobic substituent (>62.5 μM).

N,O-Chelating quinoline-based half-sandwich organorhodium and -iridium complexes: synthesis, antiplasmodial activity and preliminary evaluation as transfer hydrogenation catalysts for the reduction of NAD.

Two Rh(iii) and Ir(iii) half-sandwich quinoline-based complexes were synthesised and evaluated for their in vitro antiplasmodial activity against the chloroquine-sensitive NF54 and multi-drug resistant K1 strains of the human malaria parasite, Plasmodium falciparum. These half-sandwich organometallic complexes can also facilitate transfer hydrogenation, by converting β-nicotinamide adenine dinucleotide (NAD+) to its reduced form (NADH) in the presence of sodium formate. Co-administration of the iridium(iii) complex with sodium formate enhances the antiplasmodial activity in the chloroquine-resistant (K1) strain of Plasmodium falciparum, intimating that metal-mediated transfer hydrogenations can be achieved in malarial parasitic cells.

3D-QSAR Modeling and Synthesis of New Fusidic Acid Derivatives as Antiplasmodial Agents.

Wide spread Plasmodium falciparum ( P. falciparum) resistance has compromised existing antimalarial therapies to varying degrees. Novel agents, able to circumvent antimalarial drug resistance, are therefore needed. Fusidic acid is a unique antibiotic with a unique mode of action, which has shown weak in vitro antiplasmodial activity. Toward identifying new fusidic acid derivatives with superior antiplasmodial activity, a 3D-QSAR model was developed based on the antiplasmodial activity of previously synthesized fusidic acid derivatives. The validated Hypo 2 model was used as the 3D-structural search query to screen a fusidic acid-based combinatorial library. On the basis of the predicted activity and pharmacophore fit value, eight virtual hit compounds were selected and synthesized, including C-21 amide and C-3 ether derivatives. All synthesized hit compounds showed superior antiplasmodial activity compared to fusidic acid. Two C-21 amide derivatives displayed significant activity against the drug-sensitive NF54 strain with IC50 values of 0.3 μM and 0.7 μM, respectively. These two derivatives also displayed activity against the multidrug-resistant K1 strain, with an IC50 value of 0.2 μM and were found to be relatively noncytotoxic.

Antiplasmodial activity of two medicinal plants against clinical isolates of Plasmodium falciparum and Plasmodium berghei infected mice.

Malaria is an infectious and deadly parasitic disease, associated with fever, anaemia and other ailments. Unfortunately the upsurge of plasmodium multidrug resistant constrained researchers to look for new effective drugs. Medicinal plants seem to be an unquenchable source of bioactive principles in the treatment of various diseases. The aim of this study was to assess the antiplasmodial activity of two Ivorian medicinal plants. The in vitro activity was evaluated against clinical isolates and Plasmodium falciparum K1 multidrug resistant strain using the fluorescence based SYBR green I assay. The in vivo bioassay was carried out using the classical 4day suppressive and curative tests on Plasmodium berghei infected mice. Results showed that the in vitro bioassay of both plant extracts were found to exhibit a promising and moderate antiparasitic effects on clinical isolates (5µg/mL<IC50<15µg/mL) and Plasmodium falciparum multidrug resistant K1 strain (15µg/mL<IC50<50µg/mL). Furthermore, the in vivo antiplasmodial screening of both extracts showed a significant decrease in parasitemia, which was dose-dependent. Body temperature in mice treated with both extracts at experimental doses increased, compared to the negative control group and was dose-dependent. As for mice body weight a significant decrease (p<0.001) was noticed in the negative control group compared to tested groups of animals. The hydroethanolic stem bark extract of Anthocleista djalonensis A Chev and leaves extract of Ziziphus mauritiana Lam exhibited anti-malarial activities. Therefore, the bioactive compounds of both plant extracts need to be investigated.

Synthesis and biological characterisation of ester and amide derivatives of fusidic acid as antiplasmodial agents

A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum. Most of these derivatives showed a 4–49 and 5–17-fold increase in activity against NF54 and KI strains, respectively, as compared to FA and had a good selectivity index. These derivatives are stable over the incubation period and do not appear to be prodrugs of fusidic acid.

Study of Antiparasitic and Cytotoxicity of the Aqueous, the 80% Methanol Extract and Its Fractions, and the Acute Toxicity of the Aqueous Extract of &amp;lt;i&amp;gt;Brucea sumatrana&amp;lt;/i&amp;gt; (Simaroubaceae) Leaves Collected in Mai-Ndombe, Democratic Republic of Congo

Results from the in vitro evaluation of the antiparasitaire activity of the aqueous extract, the 80% methanol extract and its fractions from the leaves of Brucea sumatrana against Trypanosoma brucei brucei, T. cruzi, Leishmania infantum, the multidrug-resistant K1 and chloroquine-sensitive NF54 strains of Plasmodium falciparum indicated that all samples from the leaves extract presented interesting antiparasitaire activity at different extents. The 80% methanol extract, its chloroform acid, petroleum ether and 80% methanol soluble fractions and the aqueous extract exhibited strong activity against Trypanosoma b. brucei, T. cruzi, L. infantum and the multidrug-resistant K1 strain of P. falciparum with IC50 values from P. falciparum with IC50 values ranging from 50) 50 was estimated to be greater than 5 g/kg. In addition, it did not significantly modify the concentration levels of some evaluated biochemical and hematological parameters in treated rats. These results constitute a scientific validation supporting and justifying the traditional use of the leaves of B. sumatrana for the treatment of malaria, sleeping sickness and at some extent Chagas disease.

Antiprotozoal and cytotoxic activities, and the acute toxicity of extracts from of Brucea sumatrana Roxb. (Simaroubaceae) leaves collected in Mai-Ndombe, Democratic Republic of Congo

Results from the in vitro evaluation of the antiprotozoal activity of the aqueous extract, the 80% methanol extract and its fractions from the leaves of Brucea sumatrana against Trypanosoma brucei brucei, Trypanosoma cruzi, Lesihmania infantum, the multidrug-resistant K1 and chloroquine-sensitive NF54 strains of Plasmodium falciparum indicated that all samples from the leaves extract presented interesting antiprotozoal activity at different extents. The 80% methanol extract, its chloroform acid, petroleum ether and 80% methanol soluble fractions and the aqueous extract exhibited strong activity against Trypanosoma b. brucei, T. cruzi, L. infantum and the multidrug-resistant K1 strain of P. falciparum with IC50 values from < 0.25 to 4.35 µg/ml as well as against chloroquine-sensitive NF54 strain of P. falciparum with IC50 values ranging from < 0.02 to 2.0.4 µg/ml. Most samples were cytotoxic against MRC-5 cell lines (0.2 < cytotoxic concentration 50 (CC50) < 24.5 µg/ml) and showed good selective effect against all tested parasites. In acute toxicity, the aqueous extract was found to be non-toxic and its LD50 was estimated to be greater than 5 g/kg. In addition, it did not significantly modify the concentration levels of some evaluated biochemical and hematological parameters in rats. These results constitute a scientific validation supporting and justifying the traditional use of the leaves of B. sumatrana for the treatment of malaria, sleeping sickness and at some extent Chaga disease. Key words: Brucea sumatrana, Simaroubaceae, leaves, extracts, antiprotozoal activity, cytotoxic activity, acute toxicity.

QSAR and pharmacophore modeling of diverse aminothiazoles and aminopyridines for antimalarial potency against multidrug-resistant Plasmodium falciparum

Artemisinin antimalarials are the frontline and effective drugs used worldwide for the treatment of deadly Plasmodium falciparum malaria. But the recent reports of artemisinin resistance have created the urgent need to discover new molecules against single and multidrug-resistant strains of P. falciparum. In this background, we have developed here 2D-quantitative structure–activity relationship (2D-QSAR) and 3D-pharmacophore models using aminothiazole and aminopyridine compounds for their activity against multidrug-resistant strain (k1) of P. falciparum. Based on the internal (Q 2), external (R pred 2 ), overall validation (\(\overline{{r_{m(Overall)}^{2} }}\)) metrics, and number of descriptors used for model development, a QSAR equation developed from a genetic function algorithm having both linear and spline terms was found to be the best model (Q 2 = 0.675; R pred 2 = 0.720; \(\overline{{r_{m(Overall)}^{2} }}\)= 0.617). The pharmacophore models were developed in order to unveil the structural requirements for the activity, and to classify the compounds into more active and less active antimalarials against the multidrug-resistant strain (k1) of P. falciparum. The best pharmacophore model (Hypo-1) with a correlation coefficient of 0.932 showed one hydrogen bond acceptor, one hydrophobic aliphatic, and two ring aromatic features as the essential structural requirements for the antimalarial activity. The pharmacophore model (Hypo-1) also shows 86.00 % correct classification of more active compounds of the test set against the multidrug-resistant (k1) strain of P. falciparum. Both the models could be utilized further for the prediction of antimalarial potency of aminothiazole and aminopyridine compounds against multidrug-resistant P. falciparum.

Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate

BackgroundDrug repurposing or repositioning refers to the usage of existing drugs in diseases other than those it was originally used for. For diseases like malaria, where there is an urgent need for active drug candidates, the strategy offers a route to significantly shorten the traditional drug development pipelines. Preliminary high-throughput screens on patent expired drug libraries have recently been carried out for Plasmodium falciparum. This study reports the systematic and objective further interrogation of selected compounds reported in these studies, to enable their repositioning as novel stand-alone anti-malarials or as combinatorial partners.MethodsSYBR Green flow cytometry and micro-titre plate assays optimized in the laboratory were used to monitor drug susceptibility of in vitro cultures of P. falciparum K1 parasite strains. Previously described fixed-ratio methods were adopted to investigate drug interactions.ResultsEmetine dihydrochloride hydrate, an anti-protozoal drug previously used for intestinal and tissue amoebiasis was shown to have potent inhibitory properties (IC50 doses of ~ 47nM) in the multidrug resistant K1 strain of P. falciparum. The sum 50% fractional inhibitory concentration (∑FIC50, 90) of the interaction of emetine dihydrochloride hydrate and dihydroartemisinin against the K1 strains of P. falciparum ranged from 0.88-1.48.ConclusionThe results warrant further investigation of emetine dihydrochloride hydrate as a potential stand-alone anti-malarial option. The interaction between the drug and the current front line dihydroartemisinin ranged from additive to mildly antagonistic in the fixed drug ratios tested.

Chemical composition of Aspidosperma ulei Markgr. and antiplasmodial activity of selected indole alkaloids.

A new indole alkaloid, 12-hydroxy-N-acetyl-21(N)-dehydroplumeran-18-oic acid (13), and 11 known indole alkaloids: 3,4,5,6-tetradehydro-β-yohimbine (3), 19(E)-hunteracine (4), β-yohimbine (5), yohimbine (6), 19,20-dehydro-17-α-yohimbine (7), uleine (10), 20-epi-dasycarpidone (11), olivacine (8), 20-epi-N-nor-dasycarpidone (14), N-demethyluleine (15) and 20(E)-nor-subincanadine E (12) and a boonein δ-lactone 9, ursolic acid (1) and 1D,1O-methyl-chiro-inositol (2) were isolated from the EtOH extracts of different parts of Aspidosperma ulei Markgr. (Apocynaceae). Identification and structural elucidation were based on IR, MS, 1H- and 13C-NMR spectral data and comparison to literature data. The antiplasmodial and antimalarial activity of 1, 5, 6, 8, 10 and 15 has been previously evaluated and 1 and 10 have important in vitro and in vivo antimalarial properties according to patent and/or scientific literature. With the aim of discovering new antiplasmodial indole alkaloids, 3, 4, 11, 12 and 13 were evaluated for in vitro inhibition against the multi-drug resistant K1 strain of the human malaria parasite Plasmodium falciparum. IC50 values of 14.0 (39.9), 4.5 (16.7) and 14.5 (54.3) μg/mL (μM) were determined for 3, 11 and 12, respectively. Inhibitory activity of 3, 4, 11, 12 and 13 was evaluated against NIH3T3 murine fibroblasts. None of these compounds exhibited toxicity to fibroblasts (IC50 > 50 μg/mL). Of the five compounds screened for in vitro antiplasmodial activity, only 11 was active.