Furfuran lignans and a flavone from Artemisia gorgonum Webb and their in vitro activity against Plasmodium falciparum

Ortet, Risoleta; Prado, Soizic; Regalado, Erik L.; Valeriote, Frederick A.; Media, Joseph; Mendiola, Judith; Thomas, Olivier P.

doi:10.1016/j.jep.2011.09.039

Cited by 29 publications

(23 citation statements)

References 27 publications

(31 reference statements)

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“…Dependensin and its analogs were subjected to antimalarial growth inhibition assays against Plasmodium falciparum and were found to have IC 50 values ranging between 1.9 and 3.9 M (18). Sesamin and artemetin, isolated from the aerial parts of the Cape Verdean shrub Artemisia gorgonum Webb (Asteraceae), were carefully investigated and were the most active compounds (IC 50 values of 3.37 and 3.50 g/ml, respectively), without noticeable toxicity on normal mammalian cells (19). In addition, 1,2,3-triazole-tethered ␤-lactam and 7-chloroquinoline bifunctional hybrids were synthesized and showed reasonable antimalarial activities, with IC 50 values ranging from 1.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Zhao

et al. 2014

Antimicrob Agents Chemother

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dArtemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, the in vivo antimalarial activities of the lipid emulsions developed were tested in Plasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and the in vivo performance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation. Malaria is one of the most significant causes of morbidity and death worldwide. Every year, nearly one million deaths result from malaria infection, with about 85% occurring among children under 5 years of age. Indeed, one patient dies from malaria every 36 s (1).Artemisinin and its derivatives are the most important antimalarial drugs; the chemical structures of the four artemisinin compounds and lumefantrine (also known as benflumetol) are presented in Fig. 1. Artemisinin is an effective antimalarial drug isolated from the Chinese herbal medicine Artemisia annua L. It has a special sesquiterpene lactone with a peroxy group. In malaria parasites, artemisinin can be activated by intraparasitic heme iron, which catalyzes cleavage of the endoperoxide (2). Due to its unique structure and antimalarial mechanism, artemisinin has excellent antimalarial activity with low toxicity; therefore, artemisinin-based combination therapy (ACT) is recommended as the first-line strategy to treat malaria (3). After the introduction of ACT interventions, morbidity and mortality rates associated with malaria were decreased in several parts of the world (4). However, antimalarial resistance would probably be increased after longterm application of artemisinin alone. WHO reformed the malaria treatment policy in February 2004, proposing to stop the use of single antimalarial drugs (e.g., artemisinin and quinine) and promoting the use of ACTs. Recently, combination therapies such as artemether in co...

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Section: Discussionmentioning

confidence: 99%

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Zhao

et al. 2014

Antimicrob Agents Chemother

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“…It exhibits various biological activities including peroxynitrite scavenging capacity, inhibition of inducible NO synthetase, antiplasmodial activity, Ca 2+ -antagonistic activity, platelet activating factor-antagonistic activity, and chemo-preventative or therapeutic activity mediated via inhibition of mTOR kinase [2][3][4][5][6][7]. Herbal medicines and their constituents may interact with cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferases (UGTs), increasing the possibility of herb-drug interactions [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Aschantin on Cytochrome P450 and Uridine 5′-diphospho-glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

et al. 2016

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Abstract:Aschantin is a bioactive neolignan found in Magnolia flos with antiplasmodial, Ca 2+ -antagonistic, platelet activating factor-antagonistic, and chemopreventive activities. We investigated its inhibitory effects on the activities of eight major human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes of human liver microsomes to determine if mechanistic aschantin-enzyme interactions were evident. Aschantin potently inhibited CYP2C8-mediated amodiaquine N-de-ethylation, CYP2C9-mediated diclofenac 4'-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4'-hydroxylation, and CYP3A4-mediated midazolam 1'-hydroxylation, with K i values of 10.2, 3.7, 5.8, and 12.6 µM, respectively. Aschantin at 100 µM negligibly inhibited CYP1A2-mediated phenacetin O-de-ethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated bupropion hydroxylation, and CYP2D6-mediated bufuralol 1'-hydroxylation. At 200 µM, it weakly inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A6-catalyzed N-acetylserotonin glucuronidation, and UGT1A9-catalyzed mycophenolic acid glucuronidation, with IC 50 values of 131.7, 144.1, and 71.0 µM, respectively, but did not show inhibition against UGT1A3, UGT1A4, or UGT2B7 up to 200 µM. These in vitro results indicate that aschantin should be examined in terms of potential interactions with pharmacokinetic drugs in vivo. It exhibited potent mechanism-based inhibition of CYP2C8, CYP2C9, CYP2C19, and CYP3A4.

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“…The compounds were identified as arborescin ( 1 ) ( Fattorusso et al ., ), artemetin ( 2 ) (Rauter et al ., ), sesamin ( 3 ) (Li et al ., ), diayangambin ( 4 ) (Wang et al ., ), chrysosplenetin ( 5 ) (Rauter et al ., ), 24‐methylenecycloartan‐3β‐ol ( 6 ) (Ohtsu et al ., ), arglabin ( 7 ) (Adekenov et al ., ), deacetylglobicin ( 8 ) (Bohlmann et al ., ), 2α‐hydroxyarborescin ( 9 ) (Bohlmann et al ., ), sanchillin ( 10 ) (Mallabaev et al ., ), and hanphyllin ( 11 ) (Tarasov et al ., ). Compounds 4–8 were identified in A. gorgonum for the first time, although compounds 1–3 and 9–11 have also been reported as plant constituents of the same species collected on Fogo Island, Cape Verde (Ortet et al ., ; Ortet et al ., ).…”

Section: Resultsmentioning

confidence: 97%

“…(). The same group identified furfuran lignans, artemetin, and sesquiterpene lactones in A. gorgonum collected in Fogo Island (Ortet et al ., , ). Artemetin, sesamin, and four other isolated lignans showed mild antimalarial activity against a chloroquine‐resistant Plasmodium falciparum strain, although no promising cytotoxicity against human tumor cells was noticed (Ortet et al ., ).…”

Section: Introductionmentioning

confidence: 99%

In vitro Antitumoral Activity of Compounds Isolated from Artemisia gorgonum Webb

Martins

Mignon

Bastos

et al. 2014

Phytotherapy Research

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Artemisia gorgonum (Asteraceae) is an endemic plant to the Cape Verde islands and plays an important role in traditional medicine. The chloroform extract of the plant aerial parts afforded six sesquiterpene lactones, two methoxylated flavonoids, two lignans, and one tetracyclic triterpene, which were isolated by chromatographic methods and their structure established by physical and spectroscopic techniques. The cytotoxic activity of the three major constituents, namely, arborescin, artemetin, and sesamin, was evaluated on neuroblastoma (SH-SY5Y), hepatocarcinoma (HepG2), and nontumoral bone marrow stromal (S17) cell lines. The application of different concentrations of the compounds significantly decreased tumor cells viability at different extents, especially at the highest concentrations tested. Arborescin is the most promising compound as it was able to reduce tumoral cell viability with an IC50 significantly lower (229-233 μM; p < 0.01) than that of S17 cells (445 μM). Arborescin and artemetin were less toxic to nontumoral cells than the antitumoral drug tested, etoposide. Our results indicate that arborescin has a significant cytotoxic activity in vitro, more pronounced on the cancer cell lines, confirming A. gorgonum as a source of potential antitumoral molecules.

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Furfuran lignans and a flavone from Artemisia gorgonum Webb and their in vitro activity against Plasmodium falciparum

Cited by 29 publications

References 27 publications

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Inhibitory Effects of Aschantin on Cytochrome P450 and Uridine 5′-diphospho-glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

In vitro Antitumoral Activity of Compounds Isolated from Artemisia gorgonum Webb

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