Promising Antiplasmodial Activity Research Articles

Facile synthesis of vanillin-based novel bischalcones identifies one that induces apoptosis and displays synergy with Artemisinin in killing chloroquine resistant Plasmodium falciparum

The inherent affinity of natural compounds for biological receptors has been comprehensively exploited with great success for the development of many drugs, including antimalarials. Here the natural flavoring compound vanillin has been used as an economical precursor for the synthesis of a series of novel bischalcones whose in vitro antiplasmodial activities have been evaluated against erythrocytic stages of Plasmodium falciparum. Bischalcones 9, 11 and 13 showed promising antiplasmodial activity {Chloroquine (CQ) sensitive Pf3D7 IC50 (μM): 2.0, 1.5 and 2.5 respectively}but only 13 displayed potent activities also against CQ resistant PfDd2 and PfIndo strains exhibiting resistance indices of 1.4 and 1.5 respectively. IC90 (8 μM) of 13 showed killing activity against ring, trophozoite and schizont stages. Further, 13 initiated the cascade of reactions that culminates in programmed cell death of parasites including translocation of phosphatidylserine from inner to outer membrane leaflet, loss of mitochondrial membrane potential, activation of caspase like enzyme, DNA fragmentation and chromatin condensation. The combinations of 13 + Artemisinin (ART) exhibited strong synergy (ΣFIC50:0.46 to 0.58) while 13 + CQ exhibited mild synergy (ΣFIC50: 0.7 to 0.98) to mild antagonism (ΣFIC50: 1.08 to 1.23) against PfIndo. In contrast, both combinations showed marked antagonism against Pf3D7(ΣFIC50: 1.33 to 3.34). These features of apoptosis and strong synergy with Artemisinin suggest that bischalcones possess promising antimalarial drug-like properties and may also act as a good partner drugs for artemisinin based combination therapies (ACTs) against Chloroquine resistant P. falciparum.

ANTI-PLASMODIAL ACTIVITY OF SOME MEDICINAL PLANTS USED FOR TREATMENT OF MALARIA AND SYNERGISM OF METHANOLIC EXTRACTS OF CARISSA EDULIS AND ARTEMISIA ANNUA

The increasing prevalence and distribution of malaria has been attributed to a number of factors, one of them being the emergence and spread of drug resistant parasites. Efforts are now being directed towards the discovery and development of new chemically diverse anti-malarial agents. The present study reports on the in vitro anti-plasmodial activity of 15 selected medicinal plants used widely by the traditional healers to treat malaria in the North Rift parts of Kenya. The plant extracts were tested for in vitro activity against chloroquin-senitive (D6) strains of plasmodium falciparum parasites. Of the 15 species assayed, 40% showed promising anti-plasmodial activity of IC50 ≤ 10 µg/ml, while another 40% showed moderate activity of IC50 between 10 – 50 µg/ml and 20% had weak activity of IC50 between 50 – 100 µg/ml. These results justify the correlation between traditional uses of the plants with their bioactivity. Synergism between total extract of Atemisia annua and Carissa edulis ware also analyzed using combination ratios of 10:90 to 90:10 respectively against P.falciparum parasites. This led to the identification of anti-malarial combination therapy of methanolic extracts of the two plants with sum of fraction inhibiting concentration (FIC) of 0.74 at 50% combination ratios. These results support a rational rather than random approach to the selection of anti-plasmodial screening candidates, and identify a number of promising plants for further investigation as plant-based anti-malarial agents.

EVALUATION OF THE ANTIMALARIAL POTENTIAL OF STREPTOMYCES SP.

Objective: Isolate, screen and identify Streptomyces sp. from mangrove soil from pichavaram, Tamil Nadu, India, and study the molecular identification of selected Streptomyces sp. and check the antimalarial activity for the purified compound.Methods: The16SrRNA secondary structure and the restriction sites of KMA08 were predicted using Genbank online software, respectively. Antiplasmodial activity of the 80% Ethyl acetate extract of Streptomyces sp. against chloroquine-sensitive Plasmodium berghei in mice using the 4 days suppression test was conducted. A total of 30 mice assigned to 5 groups of 6 animals each were infected with chloroquine-sensitive (P. berghei) intraperitoneally. The Ethyl acetate extract (10, 20, and 30 ml/kg), standard drug (chloroquine, 10 mg/kg) and distilled water were administered orally daily for the treatment period. Percent Parasitemia was determined on the 5th day from Giemsa stained smears obtained from tail vein and percent parasitemia suppression was calculated. Daily measurement of rectal temperature was also taken while body weight and packed cell volume were recorded on day 0 and 5.Results: Results showed the extract produced a dose-dependent reduction in parasite density compared to the control group. Percept parasitemia calculation revealed 21.3, 65.3, and 80.5% inhibition at 10, 20, and 30 ml/kg of the extract, respectively.Conclusion: The study revealed the present work indicated that Streptomyces sp. has as promising antiplasmodial activity against chloroquine sensitive P. berghei in a dose-dependent. As part of the drug discovery process, these promising finding may contribute to the medicinal and pharmaceutical field for malarial treatment.

In Vivo Antimalarial Activity of the 80% Methanolic Root Bark Extract and Solvent Fractions of Gardenia ternifolia Schumach. & Thonn. (Rubiaceae) against Plasmodium berghei.

Background Evolution of antimalarial drug resistance makes the development of new drugs a necessity. Important source in search of such drugs is medicinal plants. Gardenia ternifolia plant is used in Ethiopian traditional medicine for the treatment of malaria and is endowed with in vitro antimalarial activity. Herein, the in vivo antimalarial activity of the plant was investigated. Methods Acute toxicity was carried out using a standard procedure. A 4-day suppressive test was employed to evaluate the antimalarial effect of methanolic crude extract and solvent fractions of the plant. The curative and prophylactic effect of crude extract was further tested by Ranes's test and residual infection procedure, respectively, using Plasmodium berghei (ANKA strain) in Swiss albino mice. Results The chemosuppressive effect exerted by the crude extract and fractions ranged between 30-59% and 14-51%, respectively. Curative and prophylactic effects of the crude extract were in the range of 36-63% and 24-37%, respectively. All dose levels of the crude extract prevented loss of weight, reduction in temperature, and anemia on early and established infection. Butanol and chloroform fractions also did reverse reduction in temperature, body weight, and packed cell volume. Conclusions The results indicated that the plant has a promising antiplasmodial activity and it could be considered as a potential source to develop new antimalarial agents.

Antimalarial activity of Artemisia nilagirica against Plasmodium falciparum.

Malaria is one of the most prevalent vector borne infectious disease and a serious global health problem in the world. Treatment for malaria is commonly inadequate due to the lack of quality assured limited number of effective drugs, underline how important it is to discover new antimalarial plants from number of natural sources. In the present study, the efficacy of antimalarial activity was studied by taking six various (n-hexane, chloroform, petroleum ether, ethanol, methanol and aqueous) organic leaf extracts of Artemisia nilagirica (Clarke) Pamp. against malarial parasite Plasmodium falciparum. Promising antiplasmodial activity was found in all tested extracts; however, maximum 50% inhibitory concentration (IC50) values were noticed after 32h of incubation, which is 5.76±0.82, 7.09±1.09, 9.88±1.13, 10.24±1.52, 11.37±1.77 and 50.15±6.16µg/ml in methanol, chloroform, n-hexane, petroleum ether, ethanol and aqueous extracts, respectively. In conclusion, A. nilagirica leaf extract possesses antiplasmodial activity which may be used as a potent plant-based antimalarial drug in the future by investigating the hidden phytochemical/(s).

Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents

Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1. The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 μM, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.

In vitro antiplasmodial and cytotoxic activities of sesquiterpene lactones from Vernonia fimbrillifera Less. (Asteraceae)

Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4’-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4’-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC50 values ≤ 5 μg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).

A phenolic glycoside from Flacourtia indica induces heme mediated oxidative stress in Plasmodium falciparum and attenuates malaria pathogenesis in mice

BackgroundFlacourtia indica is especially popular among the various communities of many African countries where it is being used traditionally for the treatment of malaria. In our previous report, we have identified some phenolic glycosides from the aerial parts of F. indica as promising antiplasmodial agents under in vitro conditions. PurposeAntimalarial bioprospection of F. indica derived phenolic glycoside in Swiss mice (in vivo) with special emphasis on its mode of action. MethodsChloroquine sensitive strain of Plasmodium falciparum was routinely cultured and used for the in vitro studies. The in vivo antimalarial potential of phenolic glycoside was evaluated against P. berghei in Swiss mice through an array of parameters viz., hematological, biochemical, chemo-suppression and mean survival time. Results2-(6-benzoyl-β-d-glucopyranosyloxy)-7-(1α, 2α, 6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol (CPG), a phenolic glycoside isolated from the aerial parts of F. indica was found to exhibit promising antiplasmodial activity by arresting the P. falciparum growth at the trophozoite stage. Spectroscopic investigations reveal that CPG possesses a strong binding affinity with free heme moieties. In addition, these interactions lead to the inhibition of heme polymerization in malaria parasite, augmenting oxidative stress, and delaying the rapid growth of parasite. Under in-vivo condition, CPG exhibited significant antimalarial activity against P. berghei at 50 and 75mg/kg body weight through chemo-suppression of parasitemia and ameliorating the parasite induced inflammatory and oxidative (hepatic) imbalance in the experimental mice. ConclusionCPG was found to be a potential antimalarial constituent of F. indica with an explored mechanism of action, which also offers the editing choices for developing CPG based antimalarial chemotypes.

New derivatives of quinoline-4-carboxylic acid with antiplasmodial activity

New analogues of the recently published compound DDD107498 were prepared. Their activities were examined in vitro against the chloroquine-sensitive NF54 strain. The most active were also tested against the multiresistant K1 strain of Plasmodium falciparum. A couple of the newly synthesized compounds showed promising antiplasmodial activity and selectivity. A single compound showed adequate reduction of parasitaemia (98.1%) in mice infected with Plasmodium berghei. Survival time was doubled compared to control. The results of the biological tests of the novel compounds were compared with the activities of drugs in use. Structure-activity relationships were discussed.

English

Research and development of new antiplasmodial molecules in plant is a very important way for the development of new anti-malarial drugs. In this study, Vernonia cinerea Less (Asteraceae) was selected for its promising antiplasmodial activity because it is traditionally used in Burkina Faso to treat malaria. The aim of this study was to investigate the antiplasmodial activity of this whole plant. Five crude extracts of V. cinerea Less were prepared from the solvents of increasing polarity (CH2Cl2, CH3OH, CH3OH/H2O (1/1), H2O and alkaloids extracts). The method of Ciulei (1982) and thin layer chromatography were used for chemical characterization. The p-LDH technique was used in vitro. Extracts were evaluated in vitro for efficacy against the Plasmodium falciparum strain K1, which is resistant to chloroquine, and 3D7, which is sensitive to chloroquine. The crude extracts of alkaloids showed the IC50=4.25 μg/ml with the strains 3D7 and IC50=2.56 µg/ml with the K1 strains. The CH2Cl2 extracts showed the IC50= 8.42 µg/ml and IC50=5.85 µg/ml on strains 3D7 and K1, respectively. The CH3OH extracts showed the IC50=21.08 µg/ml, CH3OH/H2O extracts gave 41.56 µg/ml and H2O extracts gave 37.17 µg/ml on strains of P. falciparum K1. The present study highlighted the very promising antiplasmodial activity of V. cinerea Less. The most antiplasmodial activity of this plant extracts merit further study about its in vivo antiplasmodial activity in Plasmodium berghei infected mice. Key words: Vernonia cinerea Less, alkaloids, triterpenes, antiplasmodial activity, Plasmodium falciparum.

Antiplasmodial Activities of the Stem bark Extract and Compounds of Zanthoxylum gilletii (De wild) P.G. Waterman

Introduction: Multidrug resistance remains a major obstacle hindering successful antimalarial chemotherapy. In the current study, 50% methanol in dichloromethane extract and six compounds from the stem bark of Zanthoxylum gilletii were explored for their antiplasmodial potential against three strains of Plasmodium falciparum. Materials and Methods: The extract was obtained by cold percolation using 50 % MeOH in CH2Cl2 and the antiplasmodial activities were assayed using a non–radioactive Malaria SYBR Green I assay to determine a concentration that inhibits growth of 50% of parasites in culture (IC 50 ). Results and Discussion: Chromatographic separation of the crude extract yielded six known compounds including: one lignan, sesamin (1), an alkamide, fagaramide (2), three benzo [c] phenanthridine alkaloids, 8–acetonyldihydrochelerythrine (3), dihydrochelerythine (4), norchelerythrine (5) and one pentacyclic triterpenoid, lupeol (6). The extract and sesamin (1) showed promising antiplasmodial activities against the chloroquine resistant (W2), chloroquine sensitive (D6) and 3D7 strains of P. falciparum, with IC50 values of 2.52, 1.48 and 1.43 µg/mL and 5.4, 9.1 and 8.3 µM, respectively. To the best of our knowledge, this is the first report on antiplasmodial activities of the stem bark extract (50% MeOH in CH2Cl2) and compound 1–3 and 6. Furthermore, three of the isolated compounds; 1, 3, 6 are reported from this species for the first time. Conclusion: The good antiplasmodial activities exhibited by the stem bark of Z. gilletii against three different strains of P. falciparum may be attributed to the presence of 1-3 exhibiting good activities against all strains of P. falciparum.

Evaluation of the Antimalarial Effect of Ferulago angulata (Schlecht.) Boiss. Extract and Suberosin Epoxide Against Plasmodium berghei in Comparison with Chloroquine Using in-vivo Test.

Resistance to most antimalarial drugs has encouraged the development of novel drugs. An alternative source for discovering such drugs is natural products. Some Ferulago species are used in folk medicine for their sedative, tonic and anti-parasitic effects. Besides, coumarins isolated from this genus found to have in vitro anti-leishmanicidal effect. The present study is aimed to evaluate the in-vivo antimalarial activity of Ferulago angulata (Schlecht.) Boiss. extract and suberosin epoxide, using suarian mice. A rodent malaria parasite, Plasmodium berghei was used to inoculate healthy male Swiss Albino mice of age 6-8 weeks and weight 23-27 g. Hydro-alcoholic extract of F. angulata (20, 100, 300, 600 mg/Kg) and suberosin epoxide suspension (10, 30, 50, 100 mg/Kg) were administered subcutaneously. Parameters including percentage of parasitemia, suppression of parasitemia and mean survival time were determined using standard test such as peter٬s. Chemo-protective effects were exerted by the crude extract and suberosin epoxide. Maximum effect was observed with the larger doses of the crude extract and suberosin epoxide. Suberosin epoxide increased the survival time compared to chloroquine. However, the results of this study indicate that the plant has a promising anti-plasmodial activity against plasmodium berghei. Thus, it could be considered as a potential source of new antimalarial agents. Suberosin epoxide at the dose of 100 mg/Kg possesses relatively significant antimalarial effect. Chemical derivatization of the parent compound or preparation of the modified formulation is required to improve its systemic bioavailability.

Antiplasmodial activities of a Thai traditional antipyretic formulation, Bencha-Loga-Wichian: A comparative study between the roots and their substitutes, the stems

Ethnopharmacological relevanceBencha-Loga-Wichian (BLW) is a polyherbal antipyretic formulation that is comprised of Capparis micracantha, Clerodendrum indicum, Ficus racemosa, Harrisonia perforata, and Tiliacora triandra. A traditional medical textbook has documented the use of this formulation for the treatment of many types of fever, including malaria-like fever. Traditionally, BLW is composed of the root parts of those plants. However, in current practice, the stem parts are frequently substituted. Thus, this study aimed to evaluate the antiplasmodial activities of BLW and compare the efficacy between the stem and root parts. Materials and methodsBLW formulations produced from either the stem or root parts of the various constituent plants as well as the stems or roots of the individual plants were separately extracted and tested against the chloroquine-sensitive (Pf3D7) and -resistant (PfW2) strains Plasmodium falciparum using flow cytometry. The cytotoxicity against peripheral blood mononuclear cells was evaluated using the WST-8 assay to determine the selectivity index (SI). The active compounds of BLW were isolated using antiplasmodial-guided isolation and quantified using Ultra-Performance Liquid Chromatography (UPLC). ResultsThe stem and root parts of BLW and the individual plants exhibited antiplasmodial activities at the same levels with good SI values in the range of 3.55–19.74. The extracts of BLW exhibited promising antiplasmodial activity against both Pf3D7 (IC50<5µg/mL) and PfW2 (IC50=6–10µg/mL). Among the five component plants, T. triandra was the most active and exhibited an IC50<5µg/mL against both strains of parasites with SI values >10. We isolated tiliacorinine and yanangcorinine as the major active compounds (IC50<2µg/mL). However, these two compounds demonstrated cytotoxic effects (SI<1). The UPLC analysis identified these compounds in both the stem and root parts of BLW in the range of 0.57–7.66%, which correlated with the antiplasmodial activity. The concentrations of these compounds in BLW, at comparable efficacy, were much less than those at the IC50s for the single compounds alone. It suggested that synergistic interactions increased the antiplasmodial effects as well as alleviated the toxicity of the active compounds in BLW. ConclusionThis study described a promising antiplasmodial activity of BLW that had good selectivity and a toxicity-alleviating effect. The results provided scientific support for the use of this formulation for the treatment of malaria. In addition, the stem and root parts of the plants in BLW exhibited equivalent activities, which indicates the potential for the substitution of the stem parts in the formulation. Thus, we recommend additional study of the stem parts of these plants for further development on the basis of the availability and sustainability.

In-vivo antimalarial activity of aqueous leaf and bark extracts of Trema orientalis against Plasmodium berghei in mice.

The control of malaria relies on the use of chemical antimalarial, but the development of resistance necessitates research into alternatives. Trema orientalis (L.) Blume is used in Nigerian folklore medicine for the treatment of malaria. This study investigates the in vivo antiplasmodial activity of aqueous leaf and bark extracts of T. orientalis in rodent model. Swiss Albino mice weighing 23-27g were intraperitoneally infected with Plasmodium berghei. The lethal dose in mice was estimated to be greater than 5000mg/kg based on toxicity signs and death. Aqueous crude leaf and bark extracts were administered at 400, 800 and 1600mg/kg. Chloroquine was used as positive control while the negative control was treated with distilled water. Parasitemia, parasite inhibition, body weight and packed cell volume (PCV) were determined. The parasite inhibition of the leaf extracts at 400, 800 and 1600mg/kg was 51.55, 62.78 and 76.08% while that of the bark extract was 44.3, 65.82 and 74.23% respectively. The percentage parasitemia of the leaf extract at 400, 800 and 1600mg/kg decreased by 45.0, 70.3 and 74.7% while that of the bark decreased by 37.4, 53.0 and 52.0% respectively. The PCV of mice treated with 400, 800 and 1600mg/kg leaf extract were 48.85, 49.88 and 50.99% while that of the bark extract was 49.38, 48.88 and 51.94% respectively. The results indicate that the plant has a promising antiplasmodial activity against P. berghei, which validates its folkloric use.

Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum

A DMAP catalyzed synthesis of new 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines was studied, in a view to react 4-chloroquinazolines with poorly nucleophilic alcohols such as benzylic alcohols, via a simple and cheap SNAr reaction approach. A fast (1 h) general operating procedure, affording good reaction yields, was achieved under microwave irradiation. Thus, a series of 35 molecules was obtained and evaluated in vitro on the K1 multi-resistant Plasmodium falciparum strain, in parallel with a cytotoxicity assessment on the human HepG2 cell line. 5 hit-molecules were identified, presenting both promising antiplasmodial activity (1.5 μM < IC50 < 2 μM) and low cytotoxicities (25 μM < CC50 < 45 μM). Apart for 2 molecules, the global series displayed a satisfying solubility in the aqueous biological media. Structure-activity relationships showed that the molecules presenting a benzyloxy moiety were less cytotoxic than the ones bearing a phenoxy moiety at position 4 of the quinazoline ring. It also appeared that the introduction of a heteroaryl moiety afforded inactive compounds. Finally, the most active and selective molecules (Selectivity Index = 22–27) were the ones presenting either an unsubstituted benzyloxy group or a phenoxy group, this last bearing a p-bromo or an o-acetyl substituent.

Diarylheptanoids Rich Fraction ofAlnus nepalensisAttenuates Malaria Pathogenesis:In-vitroandIn-vivoStudy

Diarylheptanoids from Alnus nepalensis leaves have been reported for promising activity against filariasis, a mosquito-borne disease, and this has prompted us to investigate its anti-malarial and safety profile using in-vitro and in-vivo bioassays. A. nepalensis leaf extracts were tested in-vitro against chloroquine-sensitive Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase activity. Among all, the chloroform extract (ANC) has shown promising anti-plasmodial activity (IC50 8.06 ± 0.26 µg/mL). HPLC analysis of ANC showed the presence of diarylheptanoids. Efficacy and safety of ANC were further validated in in-vivo system using Plasmodium berghei-induced malaria model and acute oral toxicity in mice. Malaria was induced by intra-peritoneal injection of P. berghei infected red blood cells to the female Balb/c mice. ANC was administered orally at doses of 100 and 300 mg/kg/day following Peter's 4 day suppression test. Oral administration of ANC showed significant reduction of parasitaemia and increase in mean survival time. It also attributed to inhibition of the parasite induced pro-inflammatory cytokines as well as afford to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. In-vivo safety evaluation study revealed that ANC is non-toxic at higher concentration. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis, characterization and antimicrobial evaluation of mono- and polynuclear ferrocenyl-derived amino and imino complexes

A series of ferrocenyl mono- and polynuclear complexes conjugated to imino and amino scaffolds was prepared. The imino complexes were prepared via a Schiff base condensation reaction between (E)-4-vinylferrocenylbenzaldehyde and various amines. The amino complexes were prepared by reductive amination reactions using the same precursors. The compounds were characterized using standard spectroscopic and analytical techniques including Nuclear Magnetic Resonance (NMR) spectroscopy, Infrared (IR) spectroscopy and mass spectrometry. The compounds were screened against Mycobacterium tuberculosis as well as the NF54 chloroquine-sensitive (CQS) strain of Plasmodium falciparum. Overall, the complexes showed moderate in vitro biological activity, with the ferrocenylimines exhibiting enhanced activity against M. tuberculosis compared to the corresponding amines. The ferrocenylimines also displayed moderate activity against P. falciparum, with the second-generation polyimine complex exhibiting the highest activity in vitro. The ferrocenylamines exhibit promising antiplasmodial activity, enhanced compared to the imines, with the silicon-containing derivative and the second-generation dendrimer showing good activity.

Alkyl phenols, alkenyl cyclohexenones and other phytochemical constituents from Lannea rivae (chiov) Sacleux (Anacardiaceae) and their bioactivity

Six novel compounds, 3-nonadec-14′-(Z)-enyl phenol (1a); 4,5-dihydroxy-4,2′-epoxy-5-[16′-Z-18′-E-heneicosenyldiene]-cyclohex-2-enone (2), 2,4,5-trihydroxy-2-[16′-Z-heneicosenyl]-cyclohexanone (3); 4S,6R-dihydroxy-6-[12′-Z-heptadecenyl]-cyclohex-2-enone (4a); 4S,6R-dihydroxy-6-[14′-Z-nonadecenyl]-cyclohex-2-enone (4b); and 1,2,4-trihydroxy-4-[16′-Z-heneicosenyl]-cyclohexane (5) were identified from the roots and stems of Lannea rivae in addition to the known cardanols, 3-heptadec-12′-Z-enyl phenol (1b), 3-pentadec-10′-Z-enyl phenol (1c) and 3-pentadecyl phenol (1d), sitosterol (6), sitosterol glucoside (7), taraxerone (8), taraxerol (9), E-lutein (10), myricetin (11), myricetin-3-O-α-rhamnopyranoside (12), myricetin-3-O-β-galactopyranoside (13) and (-)-epicatechin-3-O-gallate (14). The ketones 4a and 4b were isolated as a mixture and were qualitatively separated and identified by GCMS. Myricetin (11) and epicatechin gallate (14) displayed over 90 % DPPH radical-scavenging activity at 50 μg mL−1, while its glycosides (12 and 13) showed percentages of over 70 % in the same assay. The same compounds 11 and 14 showed antibacterial activity similar to erythromycin and vancomycin against Gram-positive bacteria and were also active against Gram-negative bacteria, but not as much as the cefuroxime, ciprofloxacin and nalidixic acid standards. Compounds 1a–d, 4a–b and 5 were all relatively non-toxic, while 2 (the epoxy cyclohex-2-enone) and 3 (the trihydroxy cyclohexanone) showed more toxicity than the others. These two toxic compounds, 2 and 3 also showed antiplasmodial activity with IC50 values between 0.48 and 2.05 μg mL−1. The mixture of dihydroxy cyclohex-2-enones 4a and 4b, which was far less toxic than 2 and 3, also showed promising antiplasmodial activity and may be a possible lead for further investigation as an antiplasmodial drug.

Synthesis, antimalarial and antitubercular activities of meridianin derivatives

Meridianins are marine-derived indole alkaloids, known to possess kinase inhibitory and antimalarial activities. A series of N-aryl and heteroaryl sulfonamide derivatives of meridianins were prepared and screened for antimalarial activity against D6 and W2 strains of Plasmodium falciparum. 2-Nitro-4-trifluoromethyl sulfonamide derivative 14v displayed promising antiplasmodial activity against both strains with IC50 values of 2.56 and 3.41 μM, respectively. These compounds were not cytotoxic to mammalian cell lines including VERO (monkey kidney fibroblasts), LLC-PK1 (pig kidney epithelial cells) and four cancer cell lines; SK-MEL (human malignant, melanoma), KB (human epidermal carcinoma), BT-549 (ductal carcinoma), SK-OV-3 (human ovary carcinoma) up to 25 μg/ml. Furthermore, all sulfonamide derivatives along with acyl, alkyl and C-ring modified derivatives of meridianins were screened for antitubercular activity against a sensitive strain (H37Rv) of Mycobacterium tuberculosis (Mtb), wherein several compounds showed MIC values in the range of 5.2–304.8 μM. Meridianin C (3) and meridianin G (7) showed anti-tubercular activity with MIC values of 111.1 and 304.8 μM, respectively. The C-ring modified analog 12 exhibited potent anti-tubercular activity against H37Rv strain of Mtb with MIC of 5.2 μM. Furthermore, the most potent analogs 11b and 12 were screened against two clinical isolates of M. tuberculosis INHR and MDR and one laboratory generated mutant strain RifR. These two analogs 11b and 12 displayed promising activity against these resistant strains with MIC values in the range of 5.2–187.7 μM. This is the first report on the anti-tubercular activity of this scaffold.

Evaluation of antiplasmodial activity of medicinal plants from North Indian Buchpora and South Indian Eastern Ghats.

BackgroundDevelopment of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents.MethodsInspired by their ethnobotanical reputation for being effective against febrile diseases, antiplasmodial potential of ethyl acetate extracts (EAE) and methanol extracts (ME) of 17 medicinal plants collected from the Eastern Ghats of South India and Buchpora, North India were explored against Plasmodium falciparum in vitro using the SYBR Green assay. The results were validated both by confirmation that the fall in fluorescence signal was not due to quenching effects mediated by phytochemical extracts and by Giemsa-stained microscopy.ResultsUsing EAE or ME, promising antiplasmodial activity (IC50Pf3D7 ≤ 20 μg/ml), was seen in Aerva lanata (Whole aerial parts-EAE), Anisomeles malabarica (Leaf-EAE), Anogeissus latifolia (bark-EAE), Cassia alata (leaves-EAE), Glycyrrhiza glabra (root-EAE), Juglans regia (seed-ME), Psidium guajava (leaf-ME and EAE) and Solanum xanthocarpum (Whole aerial parts-EAE). EAEs from leaves of Couroupita guianensis, Euphorbia hirta, Pergularia daemia, Tinospora cordifolia and Tridax procumbens as also ME from Ricinus communis (leaf and seed) showed good antiplasmodial activity (Pf 3D7 IC50 21 - 40 μg/ml). Moderate activity (Pf 3D7 IC50: 40–60 μg/mL) was shown by the leaf EAEs of Cardiospermum halicacabum, Indigofera tinctoria and Ricinus communis while the remaining extracts showed marginal (Pf 3D7 IC50 60 to >100 μg/ml) activities. The promising extracts showed good resistance indices (0.41 – 1.4) against the chloroquine resistant INDO strain of P. falciparum and good selectivity indices (3 to > 22.2) when tested against the HeLa cell line.ConclusionThese results provide validity to the traditional medicinal usage of some of these plants and further make a case for activity-guided purification of new pharmacophores against malaria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0564-z) contains supplementary material, which is available to authorized users.