Displaying publications 21 - 40 of 104 in total

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  1. Hospital and field traials of sulformethoxine with pyrimethamine against Malaysian strains of Plasmodium falciparum and P. vivax
    Laing AB
    Med J Malaya, 1968 Sep;23(1):5-19.
    PMID: 4237560
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  2. Fulltext Molecular Surveillance of Pfkelch13 and Pfmdr1 Mutations in Plasmodium falciparum Isolates from Southern Thailand
    Khammanee T, Sawangjaroen N, Buncherd H, Tun AW, Thanapongpichat S
    Korean J Parasitol, 2019 Aug;57(4):369-377.
    PMID: 31533403 DOI: 10.3347/kjp.2019.57.4.369
    Artemisinin-based combination therapy (ACT) resistance is widespread throughout the Greater Mekong Subregion. This raises concern over the antimalarial treatment in Thailand since it shares borders with Cambodia, Laos, and Myanmar where high ACT failure rates were reported. It is crucial to have information about the spread of ACT resistance for efficient planning and treatment. This study was to identify the molecular markers for antimalarial drug resistance: Pfkelch13 and Pfmdr1 mutations from 5 provinces of southern Thailand, from 2012 to 2017, of which 2 provinces on the Thai- Myanmar border (Chumphon and Ranong), one on Thai-Malaysia border (Yala) and 2 from non-border provinces (Phang Nga and Surat Thani). The results showed that C580Y mutation of Pfkelch13 was found mainly in the province on the Thai-Myanmar border. No mutations in the PfKelch13 gene were found in Surat Thani and Yala. The Pfmdr1 gene isolated from the Thai-Malaysia border was a different pattern from those found in other areas (100% N86Y) whereas wild type strain was present in Phang Nga. Our study indicated that the molecular markers of artemisinin resistance were spread in the provinces bordering along the Thai-Myanmar, and the pattern of Pfmdr1 mutations from the areas along the international border of Thailand differed from those of the non-border provinces. The information of the molecular markers from this study highlighted the recent spread of artemisinin resistant parasites from the endemic area, and the data will be useful for optimizing antimalarial treatment based on regional differences.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  3. Therapeutic equivalence of a low dose artemisinin formulation in falciparum malaria patients
    Wong JW, Yuen KH, Nagappan S, Shahul WS, Ho SS, Gan EK, et al.
    J Pharm Pharmacol, 2003 Feb;55(2):193-8.
    PMID: 12631411
    We have evaluated the therapeutic equivalence of a beta-cyclodextrin-artemisinin complex at an artemisinin dose of 150 mg, with a commercial reference preparation, Artemisinin 250 at a recommended dose of 250 mg. One hundred uncomplicated falciparum malarial patients were randomly assigned to orally receive either beta-cyclodextrin-artemisinin complex (containing 150 mg artemisinin) twice daily for five days or the active comparator (containing 250 mg artemisinin) twice daily for five days. The patients were hospitalized for seven days and were required to attend follow up assessments on days 14, 21, 28 and 35. All patients in both treatment groups were cured of the infection and achieved therapeutic success. At day seven of treatment, all patient blood was clear of the parasites and the sublingual temperature of all patients was less than 37.5 degrees C. Moreover, the parasite clearance time in both treatment groups was similar, being approximately three days after initiation of treatment. Comparable plasma artemisinin concentrations were observed between patients in both treatment groups at 1.5 and 3.0 h, although slightly higher levels were obtained with patients in the beta-cyclodextrin-artemisinin complex-treated group. The beta-cyclodextrin-artemisinin complex at a dose of 150 mg artemisinin was therapeutically equivalent to 250 mg Artemisinin 250. Additionally, patients receiving beta-cyclodextrin-artemisinin complex showed less variability in their plasma artemisinin concentrations at 1.5 h post-dosing, which suggested a more consistent rate of drug absorption.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  4. Susceptibility studies of Plasmodium falciparum isolates and clones against cycloguanil and pyrimethamine using the modified in vitro microtechnique
    Ang HH, Chan KL, Mak JW
    J Parasitol, 1996 Dec;82(6):1029-31.
    PMID: 8973418
    Six clones were derived from each Malaysian Plasmodium falciparum isolate and characterized for their susceptibilities against type II antifolate drugs, cycloguanil and pyrimethamine. Results showed that these isolates were of a heterogeneous population, with average IC50 values of Gombak C clones at 0.012-0.084 microM and 0.027-0.066 microM, ST 9 clones at 0.019-0.258 microM and 0.027-0.241 microM, ST 12 clones at 0.015-0.342 microM and 0.012-0.107 microM, ST 85 clones at 0.022-0.087 microM and 0.024-0.426 microM, and ST 148 clones at 0.027-0312 microM and 0.029-0.690 microM against cycloguanil and pyrimethamine, respectively. Generally, most of these clones displayed susceptibility patterns similar to their parent isolates except ST 9/A4, ST 9/A7, ST 9/B5, ST 9/D9, ST 9/D10, ST 148/A4, ST 148/A5, ST 148/A7, ST 148/F7, ST 148/F8 clones, which were sensitive at 0.027 microM, 0.019 microM, 0.022 microM, 0.063 microM, 0.037 microM, 0.031 microM, 0.042, microM, 0.042 microM, 0.062 microM, and 0.027 microM, whereas, ST 12/D7 clone was resistant at 0.342 microM, against cycloguanil respectively. However, ST 9/A4, ST 9/D8, ST 12/D5, ST 85/A5, ST 85/B3, ST 85/B4, ST 85/D3, ST 85/D7, ST 148/A6, and ST 148/A7 clones were resistant to pyrimethamine at 0.158 microM, 0.241 microM, 0.107 microM, 0.223 microM, 0.393 microM, 0.402 microM, 0.426 microM, 0.115 microM, 0.690 microM, and 0.520 microM, respectively.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  5. Fulltext A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
    Zhang R, Suwanarusk R, Malleret B, Cooke BM, Nosten F, Lau YL, et al.
    J Infect Dis, 2016 Jan 1;213(1):100-4.
    PMID: 26136472 DOI: 10.1093/infdis/jiv358
    Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  6. Malaria--an overview
    Gilles HM
    J Infect, 1989 Jan;18(1):11-23.
    PMID: 2644358
    The epidemiology, clinical features, diagnosis, prognosis, management, chemotherapy and chemoprophylaxis of malaria are reviewed.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  7. Opantimycin A, a new metabolite isolated from Streptomyces sp. RK88-1355
    Nogawa T, Okano A, Lim CL, Futamura Y, Shimizu T, Takahashi S, et al.
    J Antibiot (Tokyo), 2017 02;70(2):222-225.
    PMID: 27599762 DOI: 10.1038/ja.2016.113
    Matched MeSH terms: Plasmodium falciparum/drug effects
  8. Fulltext Influence of the pfmdr1 Gene on In Vitro Sensitivities of Piperaquine in Thai Isolates of Plasmodium falciparum
    Mungthin M, Watanatanasup E, Sitthichot N, Suwandittakul N, Khositnithikul R, Ward SA
    Am J Trop Med Hyg, 2017 03;96(3):624-629.
    PMID: 28044042 DOI: 10.4269/ajtmh.16-0668
    Piperaquine combined with dihydroartemisinin is one of the artemisinin derivative combination therapies, which can replace artesunate-mefloquine in treating uncomplicated falciparum malaria in Thailand. The aim of this study was to determine the in vitro sensitivity of Thai Plasmodium falciparum isolates against piperaquine and the influence of the pfmdr1 gene on in vitro response. One hundred and thirty-seven standard laboratory and adapted Thai isolates of P. falciparum were assessed for in vitro piperaquine sensitivity. Polymorphisms of the pfmdr1 gene were determined by polymerase chain reaction methods. The mean and standard deviation of the piperaquine IC50 in Thai isolates of P. falciparum were 16.7 ± 6.3 nM. The parasites exhibiting chloroquine IC50 of ≥ 100 nM were significantly less sensitive to piperaquine compared with the parasite with chloroquine IC50 of < 100 nM. No significant association between the pfmdr1 copy number and piperaquine IC50 values was found. In contrast, the parasites containing the pfmdr1 86Y allele exhibited significantly reduced piperaquine sensitivity. Before nationwide implementation of dihydroartemisinin-piperaquine as the first-line treatment in Thailand, in vitro and in vivo evaluations of this combination should be performed especially in areas where parasites containing the pfmdr1 86Y allele are predominant such as the Thai-Malaysian border.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  9. Intraspecific variation in Plasmodium falciparum
    Aikawa M, Ward RA
    Am J Trop Med Hyg, 1974 Jul;23(4):570-3.
    PMID: 4367833
    Matched MeSH terms: Plasmodium falciparum/drug effects
  10. Antimalarial drug susceptibility of Plasmodium falciparum isolates from forest fringe dwelling aborigines (Orang Asli) of Peninsular Malaysia
    Lambros C, Davis DR, Lewis GE
    Am J Trop Med Hyg, 1989 Jul;41(1):3-8.
    PMID: 2669543 DOI: 10.4269/ajtmh.1989.41.1.TM0410010003
    The drug susceptibility of 70 isolates of Plasmodium falciparum to standard and experimental antimalarials was evaluated using a radioisotope microdilution method. All isolates were from forest fringe dwelling Orang Asli, the aborigines of Peninsular Malaysia. The geometric mean IC50 values were: chloroquine, 10 ng/ml; amodiaquine, 4.7 ng/ml; mefloquine, 2.8 ng/ml; quinine, 40.5 ng/ml; halofantrine, 1.5 ng/ml; enpiroline, 3 ng/ml; and pyrimethamine, 21 ng/ml. Four isolates exhibited decreased susceptibility to chloroquine (IC50 greater than 60 ng/ml), and one exhibited decreased susceptibility to quinine (IC50 = 161 ng/ml). Three isolates showed decreased susceptibility to mefloquine (IC50 = 10-11 ng/ml). The lack of drug pressure may account for the high prevalence of P. falciparum isolates susceptible to chloroquine.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  11. Fulltext Falciparum malaria resistant to Fansidar (sulphadoxine-pyrimethamine) occurring in three children of the same family
    Ponnampalam JT
    Singapore Med J, 1982 Feb;23(1):37-8.
    PMID: 7051329
    Three cases of multiple drug resistant falciparum malaria in the same family are described. It is interesting to note that faIciparum malaria resistant to Fansidar has not as yet been reported in adults from West Malaysia up to the present time, although resistance to the drug in children is being encountered not infrequently. This presents a serious paediatric problem because malaria causes the highest incidence of mortality and morbidity in this age group in a proportion of the rural population.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  12. Fulltext Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
    Das S, Kar A, Manna S, Mandal S, Mandal S, Das S, et al.
    Sci Rep, 2021 05 11;11(1):9946.
    PMID: 33976269 DOI: 10.1038/s41598-021-89295-0
    Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P 
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  13. Fulltext Heterologous Expression of a Novel Drug Transporter from the Malaria Parasite Alters Resistance to Quinoline Antimalarials
    Tindall SM, Vallières C, Lakhani DH, Islahudin F, Ting KN, Avery SV
    Sci Rep, 2018 02 06;8(1):2464.
    PMID: 29410428 DOI: 10.1038/s41598-018-20816-0
    Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  14. Epidemiology of malaria in Malaysia
    Rahman KM
    Rev. Infect. Dis., 1982 9 1;4(5):985-91.
    PMID: 6755616
    Malaria is a major public health problem in Malaysia, particularly in peninsular Malaysia and the state of Sabah. An eradication program started in the states of Sabah and Sarawak in 1961 initially was remarkably successful. A similar but staged program was started in peninsular Malaysia in 1967 and was also quite successful. However, a marked upsurge in incidence in Sabah in 1975-1978 showed that malaria is still a major hazard. The disease leads to great economic losses in terms of the productivity of the labor force and the learning capacity of schoolchildren. The topography, the climate, and the migrations of the people due to increased economic activity are similar in peninsular Malaysia, Sabah, and Sarawak. However, the epidemiologic picture differs strikingly from area to area in terms of species of vectors, distribution of parasitic species, and resistance of Plasmodium falciparum to chloroquine. Likewise, the problems faced by the eradication or control programs in the three regions are dissimilar. Because solutions to only some of these problems are possible, the eradication of malaria in Malaysia is not likely in the near future. However, the situation offers an excellent opportunity for further studies of antimalaria measures.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  15. Melatonin effects on Plasmodium life cycle: new avenues for therapeutic approach
    Srinivasan V, Ahmad AH, Mohamed M, Zakaria R
    Recent Pat Endocr Metab Immune Drug Discov, 2012 May;6(2):139-47.
    PMID: 22537380
    Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin levels and thereby arresting the growth and elimination of malarial parasites from the blood of the host are all cited in the paper. The purpose of the paper is to highlight the importance of melatonin acting as a cue for Plasmodium faciparum growth and to discuss the ways of curbing the effects of melatonin on Plasmodium growth and for arresting its life cycle, as a method of eliminating the parasite from the host.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  16. Anti-plasmodial activity of aqueous neem leaf extract mediated green synthesis-based silver nitrate nanoparticles
    Ghazali SZ, Mohamed Noor NR, Mustaffa KMF
    Prep Biochem Biotechnol, 2022;52(1):99-107.
    PMID: 33890844 DOI: 10.1080/10826068.2021.1913602
    The objective of this study is to synthesize neem-silver nitrate nanoparticles (neem-AgNPs) using aqueous extracts of Azadirachta indica A. Juss for malaria therapy. Neem leaves collected from FRIM Malaysia were authenticated and extracted using Soxhlet extraction method. The extract was introduced to 1 mM of silver nitrate solution for neem-AgNPs synthesis. Synthesized AgNPs were further characterized by ultraviolet-visible spectroscopy and the electron-scanning microscopy. Meanwhile, for the anti-plasmodial activity of the neem-AgNPs, two lab-adapted Plasmodium falciparum strains, 3D7 (chloroquine-sensitive), and W2 (chloroquine-resistant) were tested. Red blood cells hemolysis was monitored to observe the effects of neem-AgNPs on normal and parasitized red blood cells. The synthesized neem-AgNPs were spherical in shape and showed a diameter range from 31-43 nm. When compared to aqueous neem leaves extract, the half inhibitory concentration (IC50) of the synthesized neem-AgNPs showed a four-fold IC50 decrease against both parasite strains with IC50 value of 40.920 µg/mL to 8.815 µg/mL for 3D7, and IC50 value of 98.770 µg/mL to 23.110 µg/mL on W2 strain. The hemolysis assay indicates that the synthesized neem-AgNPs and aqueous extract alone do not have hemolysis activity against normal and parasitized red blood cells. Therefore, this study shows the synthesized neem-AgNPs has a great potential to be used for malaria therapy.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  17. Fulltext Effect of HIV and malaria parasites co-infection on immune-hematological profiles among patients attending anti-retroviral treatment (ART) clinic in Infectious Disease Hospital Kano, Nigeria
    Jegede FE, Oyeyi TI, Abdulrahman SA, Mbah HA, Badru T, Agbakwuru C, et al.
    PLoS One, 2017;12(3):e0174233.
    PMID: 28346490 DOI: 10.1371/journal.pone.0174233
    BACKGROUND: Human immunodeficiency virus (HIV) and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria.

    OBJECTIVE: To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement.

    METHODS: This was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants' characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml) was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables.

    RESULTS: Of the 761 HIV infected, 64% were females, with a mean age of ± (SD) 37.30 (10.4) years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498) and gender (p = 0.789). A significantly (p = 0.026) higher prevalence (35.2%) of co-infection was observed among non-ART patients compared to (26%) ART patients. Prevalence of co-infection was significantly lower (20.0%) among cotrimoxazole users compared to those not on cotrimoxazole (37%). The same significantly lower co-infection prevalence (22.5%) was observed among treated bed net users compared to those not using treated bed nets (42.9%) (p = 0.001). Out of 16 hematology profiles evaluated, six showed significant difference between the two groups (i) packed cell volume (p = <0.001), (ii) mean cell volume (p = 0.005), (iii) mean cell hemoglobin concentration (p = 0.011), (iv) absolute lymphocyte count (p = 0.022), (v) neutrophil percentage count (p = 0.020) and (vi) platelets distribution width (p = <0.001). Current mean CD4 count cell/μl (349±12) was significantly higher in HIV infected only compared to co-infected (306±17), (p = 0.035). A significantly lower mean CD4 count (234.6 ± 6.9) was observed among respondents on ART compared to non-ART (372.5 ± 13.2), p<0.001, mean difference = -137.9).

    CONCLUSION: The study revealed a high burden of HIV and malaria co-infection among the studied population. Co-infection was significantly lower among patients who use treated bed nets as well as cotrimoxazole chemotherapy and ART. Six hematological indices differed significantly between the two groups. Malaria and HIV co-infection significantly reduces CD4 count. In general, to achieve better management of all HIV patients in this setting, diagnosing malaria, prompt antiretroviral therapy, monitoring CD4 and some hematology indices on regular basis is critical.

    Matched MeSH terms: Plasmodium falciparum/drug effects
  18. Semisynthetic 15-O-acyl- and 1,15-di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials
    Chan KL, Choo CY, Abdullah NR
    Planta Med, 2005 Oct;71(10):967-9.
    PMID: 16254833 DOI: 10.1055/s-2005-864188
    Among the quassinoids isolated from Eurycoma longifolia Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of Plasmodium falciparum. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  19. Antiplasmodial and antioxidant isoquinoline alkaloids from Dehaasia longipedicellata
    Zahari A, Cheah FK, Mohamad J, Sulaiman SN, Litaudon M, Leong KH, et al.
    Planta Med, 2014 May;80(7):599-603.
    PMID: 24723007 DOI: 10.1055/s-0034-1368349
    The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  20. Fern-synthesized nanoparticles in the fight against malaria: LC/MS analysis of Pteridium aquilinum leaf extract and biosynthesis of silver nanoparticles with high mosquitocidal and antiplasmodial activity
    Panneerselvam C, Murugan K, Roni M, Aziz AT, Suresh U, Rajaganesh R, et al.
    Parasitol Res, 2016 Mar;115(3):997-1013.
    PMID: 26612497 DOI: 10.1007/s00436-015-4828-x
    Malaria remains a major public health problem due to the emergence and spread of Plasmodium falciparum strains resistant to chloroquine. There is an urgent need to investigate new and effective sources of antimalarial drugs. This research proposed a novel method of fern-mediated synthesis of silver nanoparticles (AgNP) using a cheap plant extract of Pteridium aquilinum, acting as a reducing and capping agent. AgNP were characterized by UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). Phytochemical analysis of P. aquilinum leaf extract revealed the presence of phenols, alkaloids, tannins, flavonoids, proteins, carbohydrates, saponins, glycosides, steroids, and triterpenoids. LC/MS analysis identified at least 19 compounds, namely pterosin, hydroquinone, hydroxy-acetophenone, hydroxy-cinnamic acid, 5, 7-dihydroxy-4-methyl coumarin, trans-cinnamic acid, apiole, quercetin 3-glucoside, hydroxy-L-proline, hypaphorine, khellol glucoside, umbelliferose, violaxanthin, ergotamine tartrate, palmatine chloride, deacylgymnemic acid, methyl laurate, and palmitoyl acetate. In DPPH scavenging assays, the IC50 value of the P. aquilinum leaf extract was 10.04 μg/ml, while IC50 of BHT and rutin were 7.93 and 6.35 μg/ml. In mosquitocidal assays, LC50 of P. aquilinum leaf extract against Anopheles stephensi larvae and pupae were 220.44 ppm (larva I), 254.12 ppm (II), 302.32 ppm (III), 395.12 ppm (IV), and 502.20 ppm (pupa). LC50 of P. aquilinum-synthesized AgNP were 7.48 ppm (I), 10.68 ppm (II), 13.77 ppm (III), 18.45 ppm (IV), and 31.51 ppm (pupa). In the field, the application of P. aquilinum extract and AgNP (10 × LC50) led to 100 % larval reduction after 72 h. Both the P. aquilinum extract and AgNP reduced longevity and fecundity of An. stephensi adults. Smoke toxicity experiments conducted against An. stephensi adults showed that P. aquilinum leaf-, stem-, and root-based coils evoked mortality rates comparable to the permethrin-based positive control (57, 50, 41, and 49 %, respectively). Furthermore, the antiplasmodial activity of P. aquilinum leaf extract and green-synthesized AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of P. falciparum. IC50 of P. aquilinum were 62.04 μg/ml (CQ-s) and 71.16 μg/ml (CQ-r); P. aquilinum-synthesized AgNP achieved IC50 of 78.12 μg/ml (CQ-s) and 88.34 μg/ml (CQ-r). Overall, our results highlighted that fern-synthesized AgNP could be candidated as a new tool against chloroquine-resistant P. falciparum and different developmental instars of its primary vector An. stephensi. Further research on nanosynthesis routed by the LC/MS-identified constituents is ongoing.
    Matched MeSH terms: Plasmodium falciparum/drug effects
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