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  1. Fulltext Antiplasmodial properties of some Malaysian medicinal plants
    Noor Rain A, Khozirah S, Mohd Ridzuan MA, Ong BK, Rohaya C, Rosilawati M, et al.
    Trop Biomed, 2007 Jun;24(1):29-35.
    PMID: 17568375 MyJurnal
    Seven Malaysian medicinal plants were screened for their antiplasmodial activities in vitro. These plants were selected based on their traditional claims for treatment or to relieve fever. The plant extracts were obtained from Forest Research Institute Malaysia (FRIM). The antiplasmodial activities were carried out using the pLDH assay to Plasmodium falciparum D10 strain (sensitive strain) while the cytotoxic activities were carried out towards Madin- Darby bovine kidney (MDBK) cells using MTT assay. The concentration of extracts used for both screening assays were from the highest concentration 64 microg/ml, two fold dilution to the lowest concentration 0.03 microg/ml. Goniothalamus macrophyllus (stem extract) showed more than 60% growth inhibition while Goniothalamus scortechinii root and stem extract showed a 90% and more than 80% growth inhibition at the last concentration tested, 0.03 microg/ml. The G. scortechini (leaves extract) showed an IC50 (50% growth inhibition) at 8.53 microg/ml, Ardisia crispa (leaves extract) demonstrated an IC50 at 5.90 +/- 0.14 microg/ml while Croton argyratus (leaves extract) showed a percentage inhibition of more than 60% at the tested concentration. Blumea balsamifera root and stem showed an IC50 at 26.25 +/- 2.47 microg/ml and 7.75 +/- 0.35 microg/ ml respectively. Agathis borneensis (leaves extract) demonstrated a 50% growth inhibition at 11.00 +/- 1.41 microg/ml. The study gives preliminary scientific evidence of these plant extracts in line with their traditional claims.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  2. Fulltext Effect of Eurycoma longifolia extract on the Glutathione level in Plasmodium falciparum infected erythrocytes in vitro
    Mohd Ridzuan MA, Noor Rain A, Zhari I, Zakiah I
    Trop Biomed, 2005 Dec;22(2):155-63.
    PMID: 16883282 MyJurnal
    In the present study we examined the effect of E. longifolia methanol extract (TA164) on the GSH levels of P. falciparum infected erythrocytes and uninfected erythrocytes. Our study on parasite growth shows the IC50 and IC75 values of TA164 to be 0.17 g/ml and 6 g/ml respectively while for BSO was 25.5 g/ml and 46.5 g/ml respectively. About 95% to 100% growth inhibition of P. falciparum infected erythrocyte was observed when treated with TA164 and BSO at 16 g/ml and 64 g/ml respectively. The study on GSH contents indicated that non-infected erythrocytes treated with 6 g/ml (IC75 values) of TA164 at 24 hours incubation showed less GSH content as compared to non-treated erythrocytes. A similar observation was seen on treated trophozoite infected erythrocyte (10% parasitemia) when treated with 6 g/ml at 3 hours incubation. Analysis of the GSH contents of parasite compartments treated with TA164 at the same concentration (6 g/ml) for 3 hours incubation indicated a reduction of GSH contents. At the same concentration, TA164 did not affect the GSH contents of enriched trophozoite infected erythrocytes (60-70% parasitemia). TA164 did affect the GSH content of non-infected erythrocyte at 24 hours (accept IC50 value) as well as the parasite compartments (trophozoite infected erythrocyte and parasite itself) but fails to affect the GSH content of enriched trophozoite infected erythrocyte.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  3. 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
  4. Lansium domesticum: skin and leaf extracts of this fruit tree interrupt the lifecycle of Plasmodium falciparum, and are active towards a chloroquine-resistant strain of the parasite (T9) in vitro
    Yapp DT, Yap SY
    J Ethnopharmacol, 2003 Mar;85(1):145-50.
    PMID: 12576213
    Malaria remains a global problem in the light of chloroquine-resistant strains of Plasmodium falciparum. New compounds are needed for the development of novel antimalarial drugs. Seed, leaf, and fruit skin extracts of Lansium domesticum, a common fruit tree in South-East Asia, are used by indigenous tribes in Sabah, Malaysia for treating malaria. The skin and aqueous leaf extracts of the tree were found to reduce parasite populations of the drug sensitive strain (3D7) and the chloroquine-resistant strain (T9) of P. falciparum equally well. The skin extracts were also found to interrupt the lifecycle of the parasite. The data reported here indicate that extracts of L. domesticum are a potential source for compounds with activity towards chloroquine-resistant strains of P. falciparum.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  5. Efficacy and safety of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in endemic countries: meta-analysis of randomised controlled studies
    Naing C, Mak JW, Aung K, Wong JY
    Trans R Soc Trop Med Hyg, 2013 Feb;107(2):65-73.
    PMID: 23222952 DOI: 10.1093/trstmh/trs019
    The present review aimed to synthesise available evidence on the efficacy of dihydroartemisinin-piperaquine (DP) in treating uncomplicated Plasmodium falciparum malaria in people living in malaria-endemic countries by performing a meta-analysis of relevant studies. We searched relevant studies in electronic data bases up to December 2011. Published results from randomised controlled trials (RCTs) comparing efficacy of DP with other artemisinin-based combination therapies (ACTs), or non-ACTs, or placebo were selected. The primary endpoint was 28-day and 42-day treatment failure. We identified 26 RCTs. Many of the studies included in the present review were of high quality. Overall, DP, artesunate-mefloquine (MAS3) and artemether-lumefentrine (AL) were equally effective for reducing the risk of recurrent parasitaemia. The PCR confirmed efficacy of DP (99.5%) and MAS3 (97.7%) at day 28 exceeded 90%; both are efficacious. Comparable efficacy was also found for DP (95.6%) and AL (94.3%). The present review has documented that DP is comparable to other currently used ACTs such as MAS3 and AL in treating uncomplicated falciparum malaria. The better safety profile of DP and once-daily dosage improves adherence and its fixed co-formulation ensures that both drugs are taken together. Our conclusion is that DP has the potential to become a first-line antimalarial drug.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  6. Anti-infective activities of 11 plants species used in traditional medicine in Malaysia
    Nor Azman NS, Hossan MS, Nissapatorn V, Uthaipibull C, Prommana P, Jin KT, et al.
    Exp Parasitol, 2018 Nov;194:67-78.
    PMID: 30268422 DOI: 10.1016/j.exppara.2018.09.020
    Treatment of drug resistant protozoa, bacteria, and viruses requires new drugs with alternative chemotypes. Such compounds could be found from Southeast Asian medicinal plants. The present study examines the cytotoxic, antileishmanial, and antiplasmodial effects of 11 ethnopharmacologically important plant species in Malaysia. Chloroform extracts were tested for their toxicity against MRC-5 cells and Leishmania donovani by MTT, and chloroquine-resistant Plasmodium falciparum K1 strain by Histidine-Rich Protein II ELISA assays. None of the extract tested was cytotoxic to MRC-5 cells. Extracts of Uvaria grandiflora, Chilocarpus costatus, Tabernaemontana peduncularis, and Leuconotis eugenifolius had good activities against L. donovani with IC50 falciparum K1 with IC50 falciparum. C. costatus extract and pinoresinol increased the sensitivity of Staphylococcus epidermidis to cefotaxime. Pinoresinol demonstrated moderate activity against influenza virus (IC50 = 30.4 ± 11 μg/mL) and was active against Coxsackie virus B3 (IC50 = 7.1 ± 3.0 μg/mL). β-Amyrin from L. eugenifolius inhibited L. donovani with IC50 value of 15.4 ± 0.01 μM. Furanodienone from C. aeruginosa inhibited L. donovani and P. falciparum K1 with IC50 value of 39.5 ± 0.2 and 17.0 ± 0.05 μM, respectively. Furanodienone also inhibited the replication of influenza and Coxsackie virus B3 with IC50 value of 4.0 ± 0.5 and 7.2 ± 1.4 μg/mL (Ribavirin: IC50: 15.6 ± 2.0 μg/mL), respectively. Our study provides evidence that medicinal plants in Malaysia have potentials as a source of chemotypes for the development of anti-infective leads.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  7. Activity of Eurycoma longifolia root extract against Plasmodium falciparum in vitro
    Wernsdorfer WH, Ismail S, Chan KL, Congpuong K, Wernsdorfer G
    Wien Klin Wochenschr, 2009 Oct;121 Suppl 3:23-6.
    PMID: 19915812 DOI: 10.1007/s00508-009-1230-7
    The habitats of Eurycoma longifolia Jack, a slender tree, are jungles in Malaysia and Indonesia. It belongs to the family Simaroubaceae and is a source of quassinoids with anabolic, antimalarial and cytostatic activity. In this study, conducted during 2008 in Mae Sot, Thailand, a standardized extract of E. longifolia containing three major quassinoids, eurycomanone (1), 13,21-dihydroeurycomanone (2) and 13alpha(21)-epoxyeurycomanone (3) was evaluated for antiplasmodial activity against Plasmodium falciparum and its activity has been compared with that of artemisinin, using 38 fresh parasite isolates and assessment of inhibition of schizont maturation. The IC(50), IC(90) and IC(99) values for artemisinin were 4.30, 45.48 and 310.97 microg/l, and those for the root extract from E. longifolia 14.72, 139.65 and 874.15 microg/l respectively. The GMCOC for artemisinin was 337.81 mug/l, and for the plant extract it was 807.41 microg/l. The log-concentration probit regressions were parallel. The inhibitory activity of the E. longifolia extract was higher than that expected from the three quassinoids isolated from the plant, suggesting synergism between the quassinoids or the presence of other unidentified compounds.
    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. In vitro susceptibility studies of Plasmodium falciparum isolates and clones against type II antifolate drugs
    Ang HH, Lam CK, Wah MJ
    Chemotherapy, 1996 Sep-Oct;42(5):318-23.
    PMID: 8874969
    Six clones were derived from each Plasmodium falciparum isolate obtained from Malaysia, Africa and Thailand and were characterized against type II antifolate drugs, cycloguanil and pyrimethamine using the modified in vitro microtechnique. Results showed that these isolates were of a heterogeneous population, with 50% inhibitory concentrations of Gombak A clones at 0.0151-0.1450 and 0.0068-0.1158 microM, Gambian clones at 0.0056-0.1792 and 0.0004-0.0068 microM and TGR clones at 0.0103-0.0703 and 0.0776-0.3205 microM against cycloguanil and pyrimethamine, respectively. All clones displayed similar susceptibilities as their parent isolates except A/D3, A/D5, A/G4 and A/H7 clones which were sensitive to cycloguanil at 0.0735, 0.0151, 0.0540 and 0.0254 microM but Gm/B2 clone was resistant at 0.1792 microM, respectively. However, A/D3, TGR/B4, TGR/B7, TGR/C4, TGR/C7 and TGR/H2 clones were resistant to pyrimethamine at 0.1158, 0.1070, 0.1632, 0.1580, 0.2409 and 0.3205 microM, respectively. Further results indicated that they were pure clones compared to their parent isolates as their drug susceptibility studies were statistically different (p < 0.05).
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  11. Quantitative assessment of antimalarial activities from Malaysian Plasmodium falciparum isolates by modified in vitro microtechnique
    Hoon AH, Lam CK, Wah MJ
    Antimicrob Agents Chemother, 1995 Mar;39(3):626-8.
    PMID: 7793863
    Malaysian, TGR (Thailand), and Gambian (West African) Plasmodium falciparum isolates were cultured in vitro by the candle jar method and were characterized for their susceptibilities to present antimalarial drugs by the modified in vitro microtechnique. Results showed that 93 and 47% of the Malaysian isolates were resistant at 50% inhibitory concentrations of 0.1415 to 0.7737 and 0.1025 to 0.1975 microM, respectively, while the rest were susceptible to choloroquine and cycloguanil at 0.0376 and 0.0306 to 0.0954 microM, respectively. All isolates were susceptible to mefloquine, quinine, and pyrimethamine at 0.0026 to 0.0172, 0.0062 to 0.0854, and 0.0149 to 0.0663 microM, respectively. In contrast, the Gambian isolate was susceptible to multiple drugs at 0.0024 to 0.0282 microM; TGR was resistant to chloroquine at 0.8147 microM but was susceptible to mefloquine, quinine, cycloguanil, and pyrimethamine at 0.0024, 0.0096, 0.0143, and 0.0495 microM, respectively.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  12. Fulltext Tracking origins and spread of sulfadoxine-resistant Plasmodium falciparum dhps alleles in Thailand
    Alam MT, Vinayak S, Congpuong K, Wongsrichanalai C, Satimai W, Slutsker L, et al.
    Antimicrob Agents Chemother, 2011 Jan;55(1):155-64.
    PMID: 20956597 DOI: 10.1128/AAC.00691-10
    The emergence and spread of drug-resistant Plasmodium falciparum have been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance in P. falciparum originated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxine-resistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistant dhps alleles in Thailand.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  13. 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
  14. 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
  15. Clinical efficacy of sulfadoxine-pyrimethamine in the treatment of falciparum malaria in Sabah, Malaysia
    Tan HS, Tan PE
    Ann Acad Med Singap, 1984 Apr;13(2):170-4.
    PMID: 6388486
    One hundred and ten consecutive patients with falciparum malaria were treated with Fansidar and primaquine. Of the 61 patients who were followed up at one week, 4 (6.6%) failed to clear their parasitaemia (1 R III and 3 R II treatment failures). Of the subsequent 40 patients who were seen again at one month, another 3 (7.5%) had recrudesced (R I treatment failure). A total of 7 patients thus experienced some form of treatment failure in the cohort of 40 who completed the one month follow up. Only 1 of these 7 patients (with R III treatment failure) failed to respond to repeat Fansidar treatment, and may be the only one with true Fansidar resistance. The overall treatment failure rate of 17.5% (95% confidence interval: 6-29%) in the cohort who completed the study is consistent with the known clinical efficacy of Fansidar. These results suggest no significant Fansidar resistance in falciparum malaria found in Sabah.
    Matched MeSH terms: Plasmodium falciparum/drug effects
  16. Fulltext Plasmodium knowlesi exhibits distinct in vitro drug susceptibility profiles from those of Plasmodium falciparum
    van Schalkwyk DA, Blasco B, Davina Nuñez R, Liew JWK, Amir A, Lau YL, et al.
    Int J Parasitol Drugs Drug Resist, 2019 04;9:93-99.
    PMID: 30831468 DOI: 10.1016/j.ijpddr.2019.02.004
    New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  17. Fulltext The detection of pfcrt and pfmdr1 point mutations as molecular markers of chloroquine drug resistance, Pahang, Malaysia
    Atroosh WM, Al-Mekhlafi HM, Mahdy MA, Surin J
    Malar J, 2012;11:251.
    PMID: 22853645 DOI: 10.1186/1475-2875-11-251
    Malaria is still a public health problem in Malaysia with chloroquine (CQ) being the first-line drug in the treatment policy of uncomplicated malaria. There is a scarcity in information about the magnitude of Plasmodium falciparum CQ resistance. This study aims to investigate the presence of single point mutations in the P. falciparum chloroquine-resistance transporter gene (pfcrt) at codons 76, 271, 326, 356 and 371 and in P. falciparum multi-drug resistance-1 gene (pfmdr1) at codons 86 and 1246, as molecular markers of CQ resistance.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  18. A new antiplasmodial sterol from Indonesian marine sponge, Xestospongia sp
    Murtihapsari M, Salam S, Kurnia D, Darwati D, Kadarusman K, Abdullah FF, et al.
    Nat Prod Res, 2021 Mar;35(6):937-944.
    PMID: 31210054 DOI: 10.1080/14786419.2019.1611815
    A new antimalarial sterol, kaimanol (1), along with a known sterol, saringosterol (2) was isolated from the Indonesian Marine sponge, Xestospongia sp. The chemical structure of the new compound was determined on the basis of spectroscopic evidences and by comparison to those related compounds previously reported. Isolated compounds, 1 and 2 were evaluated for their antiplasmodial effect against Plasmodium falciparum 3D7 strains. Compounds 1 and 2 exhibited antiplasmodial activity with IC50 values of 359 and 0.250 nM, respectively.
    Matched MeSH terms: Plasmodium falciparum/drug effects*
  19. Evaluation of ethnopharmacologically selected Vitex negundo L. for In vitro antimalarial activity and secondary metabolite profiling
    Dwivedi MK, Shukla R, Sharma NK, Manhas A, Srivastava K, Kumar N, et al.
    J Ethnopharmacol, 2021 Jul 15;275:114076.
    PMID: 33789139 DOI: 10.1016/j.jep.2021.114076
    ETHANOPHARMACOLOGICAL RELEVANCE: Limited drugs, rise in drug resistance against frontline anti-malarial drugs, non-availability of efficacious vaccines and high cost of drug development hinders malaria intervention programs. Search for safe, effective and affordable plant based anti-malarial agents, thus becomes crucial and vital in the current scenario. The Vitex negundo L. is medicinal plant possessing a variety of pharmaceutically important compounds. The plant is used traditionally worldwide for the treatment of malaria including India and Malaysia by the indigenous tribes. In vitro studies have reported the anti-malarial use of the plant in traditional medicinal systems.

    AIM OF THE STUDY: The aim of the current study is to evaluate the traditionally used medicinal plants for in vitro anti-malarial activity against human malaria parasite Plasmodium falciparum and profiling secondary metabolite using spectroscopic and chromatographic methods. Chemical profiling of active secondary metabolites in the extracts was undertaken using LC-MS.

    MATERIALS AND METHODS: Based on the ethno-botanical data V. negundo L. was selected for in vitro anti-malarial activity against P. falciparum chloroquine-sensitive (3D7) and multidrug resistant (K1) strains using SYBR Green-I based fluorescence assay. Cytotoxicity of extracts was evaluated in VERO cell line using the MTT assay. Haemolysis assay was performed using human red blood cells. Secondary metabolites profiling was undertaken using chromatographic and spectroscopic analysis. Liquid chromatography analysis was performed using a C18, 150 X 2.1, 2.6 μm column with gradient mobile phase Solvent A: 95% (H2O: ACN), Solvent B: Acetonitrile, Solvent C: Methanol, Solvent D: 5 mM NH4 in 95:5 (H2O: ACN) at a constant flow rate of 0.250 ml/min. The LC-MS spectra were acquired in both positive and negative ion modes with electrospray ionization (ESI) source.

    RESULTS: The anti-malarial active extract of V. negundo L. leaf exhibited potent anti-malarial activity with IC50 values of 7.21 μg/ml and 7.43 μg/ml against 3D7 and K1 strains, respectively with no evidence of significant cytotoxicity against mammalian cell line (VERO) and no toxicity as observed in haemolysis assay. The HPLC-LC-MS analysis of the extract led to identification of 73 compounds. We report for the first time the presence of Sabinene hydrate acetate, 5-Hydroxyoxindole, 2(3,4-dimethoxyphenyl)-6, 7-dimethoxychromen-4-one, Cyclotetracosa-1, 13-diene and 5, 7-Dimethoxyflavanone in the anti-malarial active extract of V. negundo L. leaf. Agnuside, Behenic acid and Globulol are some of the novel compounds with no reports of anti-malarial activity so far and require further evaluation in pure form for the development of potent anti-malarial compounds.

    CONCLUSIONS: The result report and scientifically validate the traditional use of V. negundo L. for the treatment of malaria providing new avenues for anti-malarial drug development. Several novel and unknown compounds were identified that need to be further characterized for anti-malarial potential.

    Matched MeSH terms: Plasmodium falciparum/drug effects
  20. Fulltext Malaria in the Malaysian Army with particular reference to chemosuppressive use
    Supramaniam V, Datta GC, Singam V, Singh J
    Med J Malaysia, 1987 Mar;42(1):44-9.
    PMID: 3323860
    Malaria is the most important communicable disease in the field for the Malaysian soldier. His chief weapon is chemoprophylaxis. This was proguanil hydrochloride in the '50s, changed to Daraclor in 1962; since late 1985, Fansidar only is used. The incidence of malaria over the years has fluctuated widely and had its peak in 1977 at 29.7/1,000 soldiers and since then has shown a downward trend. Studies carried out to study the problem are noted briefly. Antimalarial discipline in the field, continued surveillance and integrated control measures in the base are emphasised in the fight against malaria.
    Matched MeSH terms: Plasmodium falciparum/drug effects
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