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Pete Smith - One of the best experts on this subject based on the ideXlab platform.
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Antiplasmodial Activity of compounds isolated from erythrina caffra
South African Journal of Botany, 2016Co-Authors: J C Chukwujekwu, C A De Kock, Pete Smith, F R Van Heerden, J Van StadenAbstract:Abstract Different fractions of the acetone stem bark extract of Erythrina caffra were studied for Antiplasmodial Activity using a chloroquine-sensitive (CQS) strain of Plasmodium falciparum (NF54). The hexane fraction exhibited the highest Antiplasmodial Activity (IC 50
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cyclopalladated organosilane tethered thiosemicarbazones novel strategies for improving Antiplasmodial Activity
Dalton Transactions, 2016Co-Authors: Muneebah Adams, Pete Smith, Carmen De Kock, Kelly Chibale, Linley Barnard, Lubbe Wiesner, Gregory S SmithAbstract:Two series of ferrocenyl- and aryl-derived cyclopalladated organosilane thiosemicarbazone complexes were synthesised via C–H bond activation. Selected compounds were evaluated for in vitro Antiplasmodial Activity against the chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) strains of the human malaria parasite Plasmodium falciparum. Cyclopalladation of the thiosemicarbazones resulted in Antiplasmodial activities in the low micromolar range.
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synthesis Antiplasmodial Activity and mechanistic studies of pyrimidine 5 carbonitrile and quinoline hybrids
European Journal of Medicinal Chemistry, 2015Co-Authors: Hardeep Kaur, Pete Smith, Jan Balzarini, Carmen De Kock, Kelly Chibale, Kamaljit SinghAbstract:Abstract A series of hybrids comprising of 5-cyanopyrimidine and quinoline moiety were synthesized and tested for in vitro Antiplasmodial Activity against NF54 and Dd2 strains of Plasmodium falciparum. Hybrid bearing m-nitrophenyl substituent at C-4 of pyrimidine displayed the highest Antiplasmodial Activity [IC50 = 56 nM] against the CQR (Dd2) strain, which is four–fold greater than CQ.
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in vitro Antiplasmodial Activity of triazole linked chloroquinoline derivatives synthesized from 7 chloro n prop 2 yn 1 yl quinolin 4 amine
Bioorganic & Medicinal Chemistry, 2015Co-Authors: Lebusetsa Taleli, Pete Smith, Carmen De Kock, Stephen C Pelly, Margaret A L Blackie, Willem A L Van OtterloAbstract:Abstract The synthesis and in vitro evaluation of novel triazole-linked chloroquinoline derivatives as potential Antiplasmodial agents against Plasmodium falciparum is reported. The 15 synthesized target compounds were obtained by means of a copper(I)-mediated click reaction between a variety of 1,2- and 1,3-azidoamines and 7-chloro- N -(prop-2-yn-1-yl)quinolin-4-amine in moderate to good yields (53–85%). The compounds were screened for Antiplasmodial Activity against NF54 chloroquine-sensitive and Dd2 chloroquine-resistant strains, alongside chloroquine and artesunate as reference compounds. Six of the test compounds revealed a 3–5 fold increase in Antiplasmodial Activity against chloroquine-resistant strain Dd2 compared to chloroquine. Among the six compounds with good Antiplasmodial Activity, a reduced cross-resistance relative to artesunate (>3 fold in comparison to chloroquine) was observed, mainly in derivatives that incorporated chloroquine-resistance reversing pharmacophores. A general trend for reduced chloroquine cross-resistance was also detected among 12 out of the 15 compounds tested.
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Antiplasmodial Activity of cucurbitacin glycosides from datisca glomerata c presl baill
Phytochemistry, 2013Co-Authors: Rocky Graziose, Pete Smith, Mary H Grace, Mary Ann Lila, Thirumurugan Rathinasabapathy, Patricio Rojassilva, Carmen Dekock, Alexander Poulev, Ilya RaskinAbstract:Abstract The traditionally used antimalarial plant, Datisca glomerata (C. Presl) Baill, was subjected to Antiplasmodial assay guided fractionation. This led to the isolation of seven cucurbitacin glycosides, datiscosides I–O, along with two known compounds, datiscoside and datiscoside B, from the aerial parts of D. glomerata . Their structures and relative stereochemistry were determined on the basis of mass spectrometry, 1D and 2D NMR spectroscopic data. Antiplasmodial IC 50 values were determined for all isolated compounds against a chloroquine sensitive strain of Plasmodium falciparum (D10), which were also evaluated in vitro for their antileishmanial Activity against Leishmania tarentolae . Cytotoxicity was evaluated against rat skeletal muscle cells (L6) and Chinese ovarian hamster cells (CHO). The Antiplasmodial Activity of the compounds was moderate and ranged from 7.7 to 33.3 μM. None of the compounds showed appreciable antileishmanial Activity. The compounds displayed cytotoxicity against L6 but not CHO mammalian cells.
Kelly Chibale - One of the best experts on this subject based on the ideXlab platform.
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cyclopalladated organosilane tethered thiosemicarbazones novel strategies for improving Antiplasmodial Activity
Dalton Transactions, 2016Co-Authors: Muneebah Adams, Pete Smith, Carmen De Kock, Kelly Chibale, Linley Barnard, Lubbe Wiesner, Gregory S SmithAbstract:Two series of ferrocenyl- and aryl-derived cyclopalladated organosilane thiosemicarbazone complexes were synthesised via C–H bond activation. Selected compounds were evaluated for in vitro Antiplasmodial Activity against the chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) strains of the human malaria parasite Plasmodium falciparum. Cyclopalladation of the thiosemicarbazones resulted in Antiplasmodial activities in the low micromolar range.
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synthesis Antiplasmodial Activity and mechanistic studies of pyrimidine 5 carbonitrile and quinoline hybrids
European Journal of Medicinal Chemistry, 2015Co-Authors: Hardeep Kaur, Pete Smith, Jan Balzarini, Carmen De Kock, Kelly Chibale, Kamaljit SinghAbstract:Abstract A series of hybrids comprising of 5-cyanopyrimidine and quinoline moiety were synthesized and tested for in vitro Antiplasmodial Activity against NF54 and Dd2 strains of Plasmodium falciparum. Hybrid bearing m-nitrophenyl substituent at C-4 of pyrimidine displayed the highest Antiplasmodial Activity [IC50 = 56 nM] against the CQR (Dd2) strain, which is four–fold greater than CQ.
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quinoline pyrimidine hybrids synthesis Antiplasmodial Activity sar and mode of action studies
Journal of Medicinal Chemistry, 2014Co-Authors: Kamaljit Singh, Hardeep Kaur, Carmen De Kock, Kelly Chibale, Peter J Smith, Jan BalzariniAbstract:For the treatment of malaria which affects nearly 200 million people each year and the continued exacerbation by the emergence of drug resistance to most of the available antimalarials, the “covalent bitherapy” suggests hybrid molecules to be the next-generation antimalarial drugs. In this investigation, new hybrids of 4-aminoquinoline and pyrimidine moieties that show Antiplasmodial Activity in the nM range against chloroquine-resistant as well as chloroquine-sensitive strains of Plasmodium falciparum have been prepared. Cytotoxicity evaluation and mode of action of most potent hybrid molecule have been conducted.
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synthesis Antiplasmodial Activity and β hematin inhibition of hydroxypyridone chloroquine hybrids
ACS Medicinal Chemistry Letters, 2013Co-Authors: Warren Andrew Andayi, Timothy J Egan, Jiri Gut, Philip J Rosenthal, Kelly ChibaleAbstract:A series of noncytotoxic 4-aminoquinoline-3-hydroxypyridin-4-one hybrids were synthesized on the basis of a synergistic in vitro combination of a precursor N-alkyl-3-hydroxypyridin-4-one with chloroquine (CQ) and tested in vitro against CQ resistant (K1 and W2) and sensitive (3D7) strains of Plasmodium falciparum. In vitro Antiplasmodial Activity of the precursors was negated by blocking the chelator moiety via complexation with gallium(III) or benzyl protection. None of the precursors inhibited β-hematin formation. Most hybrids were more potent inhibitors of β-hematin formation than CQ, and a correlation between Antiplasmodial Activity and inhibition of β-hematin formation was observed. Potent hybrids against K1, 3D7, and W2, respectively, were 8c (0.13, 0.004, and 0.1 μM); 8d (0.08, 0.01, and 0.02 μM); and 7g (0.07, 0.03, and 0.08 μM).
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design synthesis and Antiplasmodial Activity of hybrid compounds based on 2r 3s n benzoyl 3 phenylisoserine
ACS Medicinal Chemistry Letters, 2013Co-Authors: Peter Njogu, Philip J Rosenthal, Jiri Gut, Kelly ChibaleAbstract:A series of hybrid compounds based on (2R,3S)-N-benzoyl-3-phenylisoserine, artemisinin, and quinoline moieties was synthesized and tested for in vitro Antiplasmodial Activity against erythrocytic stages of K1 and W2 strains of Plasmodium falciparum. Two hybrid compounds incorporating (2R,3S)-N-benzoyl-3-phenylisoserine and artemisinin scaffolds were 3- to 4-fold more active than dihydroartemisinin, with nanomolar IC50 values against Plasmodium falciparum K1 strain.
Michel Frederich - One of the best experts on this subject based on the ideXlab platform.
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in vitro Antiplasmodial Activity of plants used in benin in traditional medicine to treat malaria
Journal of Ethnopharmacology, 2009Co-Authors: Joanne Bero, Mansourou Moudachirou, Michel Frederich, Habib Ganfon, Mariecaroline Jonville, Fernand Gbaguidi, Patrick Demol, Joelle QuetinleclercqAbstract:AIM OF THE STUDY: The aim of the study was to evaluate the in vitro Antiplasmodial Activity of crude extracts of 12 plant species traditionally used in Benin for the treatment of malaria in order to validate their use. MATERIALS AND METHODS: For each species, dichloromethane, methanol and total aqueous extracts were tested. The Antiplasmodial Activity of extracts was evaluated using the measurement of the plasmodial lactate dehydrogenase Activity on chloroquine-sensitive (3D7) and resistant (W2) strains of Plasmodium falciparum. The selectivity of the different extracts was evaluated using the MTT test on J774 macrophage-like murine cells and WI38 human normal fibroblasts. RESULTS: The best growth inhibition of both strains of Plasmodium falciparum was observed with the dichloromethane extracts of Acanthospermum hispidum DC. (Asteraceae) (IC(50)=7.5 microg/ml on 3D7 and 4.8 microg/ml on W2), Keetia leucantha (K. Krause) Bridson (syn. Plectronia leucantha Krause) (Rubiaceae) leaves and twigs (IC(50)=13.8 and 11.3 microg/ml on 3D7 and IC(50)=26.5 and 15.8 microg/ml on W2, respectively), Carpolobia lutea G.Don. (Polygalaceae) (IC(50)=19.4 microg/ml on 3D7 and 8.1 microg/ml on W2) and Strychnos spinosa Lam. (Loganiaceae) leaves (IC(50)=15.6 microg/ml on 3D7 and 8.9 microg/ml on W2). All these extracts had a low cytotoxicity. CONCLUSION: Our study gives some justifications for the traditional uses of some investigated plants.
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in vitro screening of some strychnos species for Antiplasmodial Activity
Journal of Ethnopharmacology, 2005Co-Authors: Genevieve Philippe, Luc Angenot, Patrick De Mol, Eric Goffin, Mariepierre Hayette, Monique Tits, Michel FrederichAbstract:The Antiplasmodial Activity of crude extracts of 19 species of Strychnos (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of Plasmodium falciparum. For each species, ethyl acetate (EtOAc) extracts were analysed and, for the most active species, methanolic (MeOH) extracts were also tested. Among them, Strychnos variabilis De Wild. seemed to be very promising (inhibitory concentration 50% (IC50) < 5 microg/ml) whereas two other species, Strychnos gossweileri Exell and Strychnos mellodora S. Moore, could be interesting (IC50 < 15 microg/ml) in further antimalarial studies.
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in vitro Antiplasmodial Activity of tithonia diversifolia and identification of its main active constituent tagitinin c
Planta Medica, 2002Co-Authors: Eric Goffin, Genevieve Philippe, Luc Angenot, Patrick De Mol, Monique Tits, Eric Ziemons, Maria Do Ceu Madureira, Ana Paula Martins, Antonio Proenca Da Cunha, Michel FrederichAbstract:The antimalarial properties of Tithonia diversifolia, an Asteraceae traditionally used to treat malaria, were investigated in vitro against three strains of Plasmodium falciparum. The ether extract from aerial parts of the plant collected in Sao Tome e Principe, demonstrated good Antiplasmodial Activity (IC 50 on FCA strain: 0.75 microg/ml). A bioassay guided fractionation of this extract led to the isolation of the known sesquiterpene lactone tagitinin C as an active component against Plasmodium (IC 50 on FCA strain: 0.33 microg/ml), but also possessing cytotoxic properties (IC 50 on HTC-116 cells: 0.706 microg/ml).
Cailean Clarkson - One of the best experts on this subject based on the ideXlab platform.
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in vitro Antiplasmodial Activity of medicinal plants native to or naturalised in south africa
Journal of Ethnopharmacology, 2004Co-Authors: Cailean Clarkson, Pete Smith, Vinesh Maharaj, Neil R Crouch, Olwen M Grace, Pamisha Pillay, Motlalepula G Matsabisa, Niresh Bhagwandin, Peter I FolbAbstract: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 antimalarial agents. The present study reports on the in vitro Antiplasmodial Activity of 134 plant taxa native to or naturalised in South Africa, representing 54 families, which were selected semi-quantitatively using weighted criteria. The plant extracts were tested for in vitro Activity against a Plasmodium falciparum strain D10 using the parasite lactate dehydrogenase (pLDH) assay. Of the 134 species assayed, 49% showed promising Antiplasmodial Activity (IC(50)< or = 10 microg/ml), while 17% were found to be highly active (IC(50)< or = 5 microg/ml). Several plant species and genera were shown for the first time to possess in vitro Antiplasmodial Activity. These results support a rational rather than random approach to the selection of Antiplasmodial screening candidates, and identify a number of promising taxa for further investigation as plant-based antimalarial agents.
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in vitro Antiplasmodial Activity of medicinal plants native to or naturalised in south africa
Journal of Ethnopharmacology, 2004Co-Authors: Cailean Clarkson, Vinesh Maharaj, Neil R Crouch, Olwen M Grace, Pamisha Pillay, Motlalepula G Matsabisa, Niresh Bhagwandin, Peter J Smith, Peter I FolbAbstract: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 antimalarial agents. The present study reports on the in vitro Antiplasmodial Activity of 134 plant taxa native to or naturalised in South Africa, representing 54 families, which were selected semi-quantitatively using weighted criteria. The plant extracts were tested for in vitro Activity against a Plasmodium falciparumstrain D10 using the parasite lactate dehydrogenase (pLDH) assay. Of the 134 species assayed, 49% showed promising Antiplasmodial Activity (IC50 ≤ 10g/ml), while 17% were found to be highly active (IC50 ≤ 5g/ml). Several plant species and genera were shown for the first time to possess in vitro Antiplasmodial Activity. These results support a rational rather than random approach to the selection of Antiplasmodial screening candidates, and identify a number of promising taxa for further investigation as plant-based antimalarial agents. © 2004 Elsevier Ireland Ltd. All rights reserved.
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synthesis and Antiplasmodial Activity in vitro of new ferrocene chloroquine analogues
Dalton Transactions, 2003Co-Authors: Paul Beagley, Cailean Clarkson, Kelly Chibale, Margaret A L Blackie, Reinout Meijboom, John R Moss, Pete SmithAbstract:The synthesis of the new compounds (7-chloroquinolin-4-yl)-N′-(1′-dimethylaminomethylferrocen-1-ylmethyl)-amine (4a) and N-(7-chloroquinolin-4-yl)-N′-(1′-dimethylaminomethylferrocen-1-ylmethyl)-ethane-1,2-diamine (6a) is reported. The key step in the synthesis is the cleavage of a ferrocene–Sn bond with n-BuLi to give a lithiumferrocenide species (10), which is then treated with an electrophile. Thus, 1′-dimethylaminomethyl-1-tri-n-butylstannyl-ferrocene (11) and subsequently 1′-dimethylaminomethylferrocene-1-carbaldehyde (7a) were synthesised from 1,1′-bis(tri-n-butylstannyl)ferrocene, employing [CH2NMe2]I and DMF to introduce the amine and then the aldehyde functionalities. In addition, the compound 1′-dimethylaminomethyl-1-lithiumferrocenide was isolated and the 1H and 13C NMR data are reported. X-Ray crystal and molecular structures are reported for compound 4a and the related compound N-(7-chloroquinolin-4-yl)-N′-(2-dimethylaminomethylferrocen-1-ylmethyl)-ethane-1,2-diamine (5a). The Antiplasmodial Activity in vitro against chloroquine sensitive and resistant strains of Plasmodium falciparum is reported and compared to a series of ferrocene, ruthenocene and phenylene analogues.
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In vitro Antiplasmodial Activity of abietane and totarane diterpenes isolated from Harpagophytum procumbens (devil's claw).
Planta Medica, 2003Co-Authors: Cailean Clarkson, William E. Campbell, Peter SmithAbstract:The development of drug resistance and resurgence of malaria has highlighted the need for new chemically diverse antimalarial drugs. This study investigates Harpagophytum procumbens DC. as a source of Antiplasmodial hit compounds. The roots of wild harvested plants as well as the aerial sections, seeds and roots of cultivated H. procumbens were evaluated for in vitro Antiplasmodial Activity. Bioassay-guided fractionation of the petroleum ether root extract yielded two diterpenes, (+)-8,11,13-totaratriene-12,13-diol (1) and (+)-8,11,13-abietatrien-12-ol (2). Campounds 1 and 2 displayed significant (IC 50 65) against two mammalian cell lines (CHO and HepG2). It was found that 1 and 2 did not modify the erythrocyte shape, which in conjunction with the cytotoxicity results, indicates selective Antiplasmodial Activity.
Peter I Folb - One of the best experts on this subject based on the ideXlab platform.
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in vitro Antiplasmodial Activity of medicinal plants native to or naturalised in south africa
Journal of Ethnopharmacology, 2004Co-Authors: Cailean Clarkson, Vinesh Maharaj, Neil R Crouch, Olwen M Grace, Pamisha Pillay, Motlalepula G Matsabisa, Niresh Bhagwandin, Peter J Smith, Peter I FolbAbstract: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 antimalarial agents. The present study reports on the in vitro Antiplasmodial Activity of 134 plant taxa native to or naturalised in South Africa, representing 54 families, which were selected semi-quantitatively using weighted criteria. The plant extracts were tested for in vitro Activity against a Plasmodium falciparumstrain D10 using the parasite lactate dehydrogenase (pLDH) assay. Of the 134 species assayed, 49% showed promising Antiplasmodial Activity (IC50 ≤ 10g/ml), while 17% were found to be highly active (IC50 ≤ 5g/ml). Several plant species and genera were shown for the first time to possess in vitro Antiplasmodial Activity. These results support a rational rather than random approach to the selection of Antiplasmodial screening candidates, and identify a number of promising taxa for further investigation as plant-based antimalarial agents. © 2004 Elsevier Ireland Ltd. All rights reserved.
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in vitro Antiplasmodial Activity of medicinal plants native to or naturalised in south africa
Journal of Ethnopharmacology, 2004Co-Authors: Cailean Clarkson, Pete Smith, Vinesh Maharaj, Neil R Crouch, Olwen M Grace, Pamisha Pillay, Motlalepula G Matsabisa, Niresh Bhagwandin, Peter I FolbAbstract: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 antimalarial agents. The present study reports on the in vitro Antiplasmodial Activity of 134 plant taxa native to or naturalised in South Africa, representing 54 families, which were selected semi-quantitatively using weighted criteria. The plant extracts were tested for in vitro Activity against a Plasmodium falciparum strain D10 using the parasite lactate dehydrogenase (pLDH) assay. Of the 134 species assayed, 49% showed promising Antiplasmodial Activity (IC(50)< or = 10 microg/ml), while 17% were found to be highly active (IC(50)< or = 5 microg/ml). Several plant species and genera were shown for the first time to possess in vitro Antiplasmodial Activity. These results support a rational rather than random approach to the selection of Antiplasmodial screening candidates, and identify a number of promising taxa for further investigation as plant-based antimalarial agents.