Displaying publications 1 - 20 of 28 in total

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  1. New alkaloids from Phoebe grandis (Nees) Merr
    Awang K, Mukhtar MR, Hadi AH, Litaudon M, Latip J, Abdullah NR
    Nat Prod Res, 2006 May 20;20(6):567-72.
    PMID: 16835089
    The alkaloidal extract of the leaves of Phoebe grandis (nees) merr. have provided two new minor alkaloids; phoebegrandine D (1), a proaporphine-tryptamine dimer, and phoebegrandine E (2), an indoloquinolizidine. This is the first report on the occurrence of an indoloquinolizidine in the Phoebe species. The crude extract also exhibited antiplasmodial activity (IC50<8 microg mL-1). The structures of the novel compounds were elucidated by spectroscopic methods, notably 2D NMR and HRMS.
    Matched MeSH terms: Antimalarials/chemistry
  2. Enantioselective analysis of primaquine and its impurity quinocide by capillary electrophoresis
    Elbashir AA, Saad B, Ali AS, Saleh MI, Aboul-Enein HY
    Biomed Chromatogr, 2009 Mar;23(3):295-301.
    PMID: 18816453 DOI: 10.1002/bmc.1113
    A capillary electrophoretic (CE) method for the baseline separation of the enantiomers of primaquine diphosphate (PQ) and quinocide (QC) (a major contaminant) in pharmaceutical formulations is proposed. Both components were separated under the following conditions: 50 mm tris phosphate buffer (pH 3.0) containing 15 mm hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as background electrolyte; applied voltage, 16 kV; capillary temperature, 25 degrees C; detection wavelength, 254 nm; hydrostatic injection, 10 s. The separations were conducted using a 35 cm length and 50 microm i.d. uncoated fused silica capillary column. Under the optimized conditions, the components were successfully separated in about 5 min. Intraday precision of migration time and corrected peak areas when expressed as relative standard deviation ranged from 0.17 to 0.45 and 2.60 to 3.94%, respectively, while the interday precision ranged from 2.59 to 4.20 and 3.15 to 4.21%, respectively. After the validation exercise, the proposed method was applied for the determination of QC impurity in PQ formulations.
    Matched MeSH terms: Antimalarials/chemistry*
  3. Determination of quinocide as impurity in primaquine tablets by capillary zone electrophoresis
    Elbashir AA, Saad B, Ali AS, Saleh MI, Aboul-Enein HY
    Biomed Chromatogr, 2009 May;23(5):464-71.
    PMID: 19016231 DOI: 10.1002/bmc.1137
    A capillary zone electrophoretic method has been developed and validated for the determination of the impurity quinocide (QC) in the antimalarial drug primaquine (PQ). Different buffer additives such as native cyclodextrins and crown ethers were evaluated. Promising results were obtained when either beta-cyclodextrin (beta-CD) or 18-crown-6 ether (18C6) were used. Their separation conditions such as type of buffer and its pH, buffer additive concentration, applied voltage capillary temperature and injection time were optimized. The use of 18C6 offers slight advantages over beta-CD such as faster elution times and improved resolution. Nevertheless, migration times of less than 5 min and resolution factors (R(s)) in the range of 2-4 were obtained when both additives were used. The method was validated with respect to selectivity, linearity, limits of detection and quantitation, analytical precision (intra- and inter-day variability) and repeatability. Concentrations of 2.12 and 2.71% (w/w) of QC were found in pharmaceutical preparations of PQ from two different manufacturers. A possible mechanism for the successful separation of the isomers is also discussed.
    Matched MeSH terms: Antimalarials/chemistry*
  4. LC-MS/MS quantitation of antimalarial drug piperaquine and metabolites in human plasma
    Aziz MY, Hoffmann KJ, Ashton M
    J Chromatogr B Analyt Technol Biomed Life Sci, 2017 Sep 15;1063:253-258.
    PMID: 28863865 DOI: 10.1016/j.jchromb.2017.06.035
    PURPOSE: This study aimed to develop a sensitive, quantitative assay for the antimalarial piperaquine (PQ) and its metabolites M1 and M2 in human plasma.

    RESULTS: Analytes were gradiently separated on a C18 column and detected with a Sciex API 4000 MS/MS with an ESI source operated in the positive ion mode with deuterated PQ as internal standard. The response was linear in the range 3.9-2508nM with a runtime of 7.0min per sample. The method was applied to clinical samples from healthy volunteers.

    CONCLUSION: This LC-MS/MS method for the simultaneous quantitation of PQ and two of its metabolites in plasma may prove helpful for assessment of metabolite safety issues in vivo.

    Matched MeSH terms: Antimalarials/chemistry
  5. Fulltext Antiplasmodial alkaloids from the bark of Cryptocarya nigra (Lauraceae)
    Nasrullah AA, Zahari A, Mohamad J, Awang K
    Molecules, 2013 Jul 08;18(7):8009-17.
    PMID: 23884132 DOI: 10.3390/molecules18078009
    A dichloromethane extract of the stem bark of Cryptocarya nigra showed strong in vitro inhibition of Plasmodium falciparum growth, with an IC50 value of 2.82 μg/mL. The phytochemical study of this extract has led to the isolation and characterization of four known alkaloids: (+)-N-methylisococlaurine (1), atherosperminine (2), 2-hydroxyathersperminine (3), and noratherosperminine (4). Structural elucidation of all alkaloids was accomplished by means of high field 1D- and 2D-NMR, IR, UV and LCMS spectral data. The isolated extract constituents (+)-N-methylisococlaurine (1), atherosperminine (2) and 2-hydroxy-atherosperminine (3) showed strong antiplasmodial activity, with IC50 values of 5.40, 5.80 and 0.75 μM, respectively. In addition, (+)-N-methylisocolaurine (1) and atherosperminine (2) showed high antioxidant activity in a DPPH assay with IC50 values of 29.56 ug/mL and 54.53 ug/mL respectively. Compounds 1 and 2 also both showed high antioxidant activity in the FRAP assay, with percentages of 78.54 and 70.66 respectively and in the metal chelating assay, with IC50 values of 50.08 ug/mL and 42.87 ug/mL, respectively.
    Matched MeSH terms: Antimalarials/chemistry
  6. 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: Antimalarials/chemistry
  7. Fulltext Stability of the antimalarial drug dihydroartemisinin under physiologically relevant conditions: implications for clinical treatment and pharmacokinetic and in vitro assays
    Parapini S, Olliaro P, Navaratnam V, Taramelli D, Basilico N
    Antimicrob Agents Chemother, 2015 Jul;59(7):4046-52.
    PMID: 25918150 DOI: 10.1128/AAC.00183-15
    Artemisinins are peroxidic antimalarial drugs known to be very potent but highly chemically unstable; they degrade in the presence of ferrous iron, Fe(II)-heme, or biological reductants. Less documented is how this translates into chemical stability and antimalarial activity across a range of conditions applying to in vitro testing and clinical situations. Dihydroartemisinin (DHA) is studied here because it is an antimalarial drug on its own and the main metabolite of other artemisinins. The behaviors of DHA in phosphate-buffered saline, plasma, or erythrocyte lysate at different temperatures and pH ranges were examined. The antimalarial activity of the residual drug was evaluated using the chemosensitivity assay on Plasmodium falciparum, and the extent of decomposition of DHA was established through use of high-performance liquid chromatography with electrochemical detection analysis. The role of the Fe(II)-heme was investigated by blocking its reactivity using carbon monoxide (CO). A significant reduction in the antimalarial activity of DHA was seen after incubation in plasma and to a lesser extent in erythrocyte lysate. Activity was reduced by half after 3 h and almost completely abolished after 24 h. Serum-enriched media also affected DHA activity. Effects were temperature and pH dependent and paralleled the increased rate of decomposition of DHA from pH 7 upwards and in plasma. These results suggest that particular care should be taken in conducting and interpreting in vitro studies, prone as their results are to experimental and drug storage conditions. Disorders such as fever, hemolysis, or acidosis associated with malaria severity may contribute to artemisinin instability and reduce their clinical efficacy.
    Matched MeSH terms: Antimalarials/chemistry*
  8. 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: Antimalarials/chemistry*
  9. Physico-chemical effects of the major quassinoids in a standardized Eurycoma longifolia extract (Fr 2) on the bioavailability and pharmacokinetic properties, and their implications for oral antimalarial activity
    Low BS, Teh CH, Yuen KH, Chan KL
    Nat Prod Commun, 2011 Mar;6(3):337-41.
    PMID: 21485270
    A simple validated LC-UV method for the phytochemical analysis of four bioactive quassinoids, 13alpha(21)-epoxyeurycomanone (EP), eurycomanone (EN), 13alpha,21-dihydroeurycomanone (ED) and eurycomanol (EL) in rat plasma following oral (200 mg/kg) and intravenous administration (10 mg/kg) of a standardized extract Fr 2 of Eurycoma longifolia Jack was developed for pharmacokinetic and bioavailability studies. The extract Fr 2 contained 4.0%, 18.5%, 0.7% and 9.5% of EP, EN, ED and EL, respectively. Following intravenous administration, EP displayed a relatively longer biological half-life (t1/2 = 0.75 +/- 0.25 h) due primarily to its lower elimination rate constant (k(e)) of 0.84 +/- 0.26 h(-1)) when compared with the t1/2 of 0.35 +/- 0.04 h and k(e) of 2.14 +/- 0.27 h(-1), respectively of EN. Following oral administration, EP showed a higher C(max) of 1.61 +/- 0.41 microg/mL over that of EN (C(max) = 0.53 +/- 0.10 microg/mL). The absolute bioavailability of EP was 9.5-fold higher than that of EN, not because of chemical degradation since both quassinoids were stable at the simulated gastric pH of 1. Instead, the higher log K(ow) value of EP (-0.43) contributed to greater membrane permeability over that of EN (log K(ow) = -1.46) at pH 1. In contrast, EL, being in higher concentration in the extract than EP, was not detected in the plasma after oral administration because of substantial degradation by the gastric juices after 2 h. Similarly, ED, being unstable at the acidic pH and together with its low concentration in Fr 2, was not detectable in the rat plasma. In conclusion, upon oral administration of the bioactive standardized extract Fr 2, EP and EN may be the only quassinoids contributing to the overall antimalarial activity; this is worthy of further investigation.
    Matched MeSH terms: Antimalarials/chemistry*
  10. Developing a validated liquid chromatography-mass spectrometric method for the simultaneous analysis of five bioactive quassinoid markers for the standardization of manufactured batches of Eurycoma longifolia Jack extract as antimalarial medicaments
    Teh CH, Murugaiyah V, Chan KL
    J Chromatogr A, 2011 Apr 8;1218(14):1861-77.
    PMID: 21367427 DOI: 10.1016/j.chroma.2011.02.014
    An extensive comparative study on the electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) mass spectrometry using automated flow injection analysis (FIA), was performed on eurycomanone (1), 13α(21)-epoxyeurycomanone (2), eurycomanol (3), eurycomanol-2-O-β-d-glucopyranoside (4), and 13,21-dihydroeurycomanone (5), the bioactive markers isolated from Eurycoma longifolia. The effects of eluent mixture (methanol or acetonitrile in water) and acidic modifiers (acetic acid, formic acid and trifluoroacetic acid) on the ionization efficiency of the markers were also investigated. The ESI in the positive ion mode with methanol containing 0.1% (v/v) acetic acid was selected for the subsequent optimization of nebulizer pressure, dry gas flow, dry gas temperature and capillary voltage to improve the sensitivity of the total ion chromatogram (TIC). Fragmentation of the analytes was further investigated by varying the capillary exit offset voltage and fragmentation amplitude in positive mode of ESI. The detection limits (LODs) were determined in isolation mode (selected ion monitoring, SIM). Their limits of detection (LODs) ranged between 0.03 and 0.1μgmL(-1) while the intra-day and inter-day precisions were less than 5.72% and 4.82%, respectively. The method was next applied for the simultaneous analysis of the markers to standardize various batches of manufactured extracts of E. longifolia for potential use as antimalarial products. Multiple Reaction Monitoring (MRM) mode was used for the quantification of analytes which gave protonated molecular ion, [M+H](+). For those without pseudo-molecular ions, SIM mode was used to quantify the analytes. The batches contained 5.65-9.95% of eurycomanone (1), 5.21-19.75% of eurycomanol (3) and 7.59-19.95% of eurycomanol-2-O-β-d-glucopyranoside (4) as major quassinoids whereas, 13α(21)-epoxyeurycomanone (2), and 13,21-dihydroeurycomanone (5) were much lower in concentrations of 0.78-3.90% and 0.47-1.76%, respectively.
    Matched MeSH terms: Antimalarials/chemistry*
  11. Sustainable Dissolution Performance of a Carrier Tailored Electrospun
    Teoh XY, Yeoh Y, Yoong LK, Chan SY
    Pharm Res, 2020 Jan 07;37(2):28.
    PMID: 31912250 DOI: 10.1007/s11095-019-2734-0
    PURPOSE: This study aims to conduct an impact investigation in the hydrophobic-hydrophilic balance as an important factor for dissolution improvement of a hydrophilic carrier-based solid dispersion system.

    METHODS: Polymeric carriers with different hydrophobic to hydrophilic ratios were used to prepare several electrospun solid dispersion formulations. Physicochemical properties and surface morphology of the samples were assessed using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), polarized light microscopy, Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD) and Scanning Electron Microscopy (SEM). Dissolution study was conducted in a non-sink condition to assess the drug release.

    RESULTS: Incorporation of a higher amount of hydrophilic component showed an improvement in formulating a fully amorphous system based on XRPD, yet the dissolution rate increment showed no significant difference from the lower. Hence, the degree of crystallinity is proven not to be the crucial factor contributing to dissolution rate improvement. The presence of a concomitant hydrophobic component, however, showed ability in resisting precipitation and sustaining supersaturation.

    CONCLUSION: Hydrophobicity in a binary carrier system plays an important role in achieving and maintaining the supersaturated state particularly for an amorphous solid dispersion. Graphical Abstract.

    Matched MeSH terms: Antimalarials/chemistry*
  12. Current progress in antimalarial pharmacotherapy and multi-target drug discovery
    Tibon NS, Ng CH, Cheong SL
    Eur J Med Chem, 2020 Feb 15;188:111983.
    PMID: 31911292 DOI: 10.1016/j.ejmech.2019.111983
    Discovery and development of antimalarial drugs have long been dominated by single-target therapy. Continuous effort has been made to explore and identify different targets in malaria parasite crucial for the malaria treatment. The single-target drug therapy was initially successful, but it was later supplanted by combination therapy with multiple drugs to overcome drug resistance. Emergence of resistant strains even against the combination therapy has warranted a review of current antimalarial pharmacotherapy. This has led to the development of the new concept of covalent biotherapy, in which two or more pharmacophores are chemically bound to produce hybrid antimalarial drugs with multi-target functionalities. Herein, the review initially details the current pharmacotherapy for malaria as well as the conventional and novel targets of importance identified in the malaria parasite. Then, the rationale of multi-targeted therapy for malaria, approaches taken to develop the multi-target antimalarial hybrids, and the examples of hybrid molecules are comprehensively enumerated and discussed.
    Matched MeSH terms: Antimalarials/chemistry
  13. Fulltext Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
    Mphahlele MJ, Mmonwa MM, Choong YS
    Molecules, 2017 Jul 02;22(7).
    PMID: 28671598 DOI: 10.3390/molecules22071099
    A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides with trifluoroacetic anhydride. The prepared compounds were evaluated for potential in vitro antiplasmodial properties. Preliminary results from antiplasmodial activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum revealed that a combination of 2-(4-flurophenyl)- and 5-(4-fluorophenyl) or 2-(4-flurophenyl)- and 4-fluorostyryl groups in compounds 3(a,f) and 4(a,g), for example, is required for biological activity for both series of compounds. Their possible mode of action against the plasmodial parasite is explained theoretically through molecular docking of the most active compounds against the parasite lactate dehydrogenase (pLDH). These compounds were docked at the entrance of NAD+ in pLDH presumably hindering entry of lactate to cause the observed inhibition effect of pLDH. The four compounds were found to exhibit low toxicity against monkey kidney Vero cells at the highest concentrations tested.
    Matched MeSH terms: Antimalarials/chemistry
  14. Fulltext Gancidin W, a potential low-toxicity antimalarial agent isolated from an endophytic Streptomyces SUK10
    Zin NM, Baba MS, Zainal-Abidin AH, Latip J, Mazlan NW, Edrada-Ebel R
    Drug Des Devel Ther, 2017;11:351-363.
    PMID: 28223778 DOI: 10.2147/DDDT.S121283
    Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated from the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg-1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 μg kg-1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model.
    Matched MeSH terms: Antimalarials/chemistry
  15. New alkaloids from Phoebe scortechinii
    Awang K, Mukhtar MR, Mustafa MR, Litaudon M, Shaari K, Mohamad K, et al.
    Nat Prod Res, 2007 Jul 10;21(8):704-9.
    PMID: 17616898
    The leaves of the Phoebe scortechinii (Gamb.) Kochummen Comb. Nov. (Lauraceae), afforded one new proaporphine-tryptamine dimer; (-)-phoebescortechiniine (1), along with two known ones; phoebegrandine A and phoebegrandine B. The proaporphine, tetrahydropronuciferine (2), was isolated for the first time as a natural product. The alkaloids were elucidated primarily by means of high field NMR and HRMS.
    Matched MeSH terms: Antimalarials/chemistry
  16. ent-Dioncophylleine A and related dehydrogenated naphthylisoquinoline alkaloids, the first Asian dioncophyllaceae-type alkaloids, from the "new"plant species Ancistrocladus benomensis
    Bringmann G, Dreyer M, Kopff H, Rischer H, Wohlfarth M, Hadi HA, et al.
    J Nat Prod, 2005 May;68(5):686-90.
    PMID: 15921410
    Three new fully dehydrogenated naphthylisoquinoline alkaloids, the 7,1'-coupled ent-dioncophylleine A (3a), the likewise 7,1'-coupled 5'-O-demethyl-ent-dioncophylleine A (4), and the 7,8'-linked dioncophylleine D (5), have been isolated from the leaves of the recently described Malaysian highland liana Ancistrocladusbenomensis. All of them lack an oxygen function at C-6; this so-called Dioncophyllaceae-type structural subclass had previously been found only in naphthylisoquinoline alkaloids from West and Central African plants. Moreover, compounds 3a and 4 are the first fully dehydrogenated, i.e., only axially chiral, naphthylisoquinoline alkaloids of this type that are optically active; compound 5, by contrast, is fully racemic, due to its configurationally unstable biaryl axis. The structural elucidation was achieved by spectroscopic and chiroptical methods. Biological activities of these alkaloids against different protozoan parasites are described.
    Matched MeSH terms: Antimalarials/chemistry
  17. Fulltext Ferroquine and its derivatives: new generation of antimalarial agents
    Wani WA, Jameel E, Baig U, Mumtazuddin S, Hun LT
    Eur J Med Chem, 2015 Aug 28;101:534-51.
    PMID: 26188909 DOI: 10.1016/j.ejmech.2015.07.009
    Malaria has been teasing human populations from a long time. Presently, several classes of antimalarial drugs are available in market, but the issues of toxicity, lower efficacy and the resistance by malarial parasites have decreased their overall therapeutic indices. Thus, the search for new promising antimalarials continues, however, the battle against malaria is far from over. Ferroquine is a derivative of chloroquine with antimalarial properties. It is the most successful of the chloroquine derivatives. Not only ferroquine, but also its derivatives have shown promising potential as antimalarials of clinical interest. Presently, much research is dedicated to the development of ferroquine derivatives as safe alternatives to antimalarial chemotherapy. The present article describes the structural, chemical and biological features of ferroquine. Several classes of ferroquine derivatives including hydroxyferroquines, trioxaferroquines, chloroquine-bridged ferrocenophanes, thiosemicarbazone derivatives, ferrocene dual conjugates, 4-N-substituted derivatives, and others have been discussed. Besides, the mechanism of action of ferroquine has been discussed. A careful observation has been made into pharmacologically significant ferroquine derivatives with better or equal therapeutic effects to that of chloroquine and ferroquine. A brief discussion of the toxicities of ferroquine derivatives has been made. Finally, efforts have been made to discuss the current challenges and future perspectives of ferroquine-based antimalarial drug development.
    Matched MeSH terms: Antimalarials/chemistry
  18. Exploring Promising Immunomodulatory Potential of Natural and Synthetic 1,3-Diphenyl-2-propen-1-one Analogs: A Review of Mechanistic Insight
    Safdar MH, Hasan H, Afzal S, Hussain Z
    Mini Rev Med Chem, 2018;18(12):1047-1063.
    PMID: 29173165 DOI: 10.2174/1389557517666171123212039
    The immune system is an intricate and coordinated nexus serving as a natural defense to preclude internal and external pathogenic insults. The deregulation in the natural balance of immunological functions as a consequence of either over expression or under expression of immune cells tends to cause disruption of homeostasis in the body and may lead to development of numerous immune system disorders. Chalcone moieties (1,3-diphenyl-2-propen-1-one) have been well-documented as ideal lead compounds or precursors to design a wide range of pharmacologically active agents to down-regulate various immune disorders. Owing to their unique structural and molecular framework, these α, β-unsaturated carbonyl-based moieties have also gained remarkable recognition due to their other multifarious pharmacological properties including antifungal, anti-inflammatory, anti-malarial, antibacterial, anti-tuberculosis, and anticancer potential. Though a great number of methodologies are currently being employed for their synthesis, this review mainly focuses on the natural and synthetic chalcone derivatives that are exclusively synthesized via Claisen-Schmidt condensation reaction and their immunomodulatory prospects. We have critically reviewed the literature and provided convincing evidence for the promising efficacy of chalcone derivatives to modulate functioning of various innate and adaptive immune players including granulocytes, mast cells, monocytes, macrophages, platelets, dendritic cells, natural killer cells, and T-lymphocytes.
    Matched MeSH terms: Antimalarials/chemistry
  19. Smart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluation
    Shah SM, Ullah F, Khan S, Shah SM, de Matas M, Hussain Z, et al.
    Drug Des Devel Ther, 2016;10:3837-3850.
    PMID: 27920499
    Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena(®) DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C-8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena(®) DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.
    Matched MeSH terms: Antimalarials/chemistry*
  20. Fulltext Median lethal dose, antimalarial activity, phytochemical screening and radical scavenging of methanolic Languas galanga rhizome extract
    Al-Adhroey AH, Nor ZM, Al-Mekhlafi HM, Mahmud R
    Molecules, 2010 Nov 16;15(11):8366-76.
    PMID: 21081857 DOI: 10.3390/molecules15118366
    The methanolic extract of Languas galanga rhizomes was investigated for antimalarial activity against Plasmodium berghei (NK65) infections in mice. The median lethal dose was determined to ascertain the safety of the extract in ICR mice of both sexes. The antimalarial activities during early and established infections, as well as the prophylactic activity were evaluated. Phytochemical screening and radical scavenging activity of the extract were also investigated to elucidate the possible mechanism of the antimalarial properties. The acute oral toxicity (LD₅₀) of Languas galanga extract in mice was established to be 4.998 mg/kg. The extract of Languas galanga rhizomes demonstrated significant antiplasmodial activity in all the three models of the antimalarial evaluations. Phytochemical screening revealed the presence of some vital antiplasmodial constituents such as terpenoids and flavonoids. The extract also exhibited a moderate capacity to scavenge the free radicals. The rhizome extract of Languas galanga thus possesses antimalarial activity, which explains the rational usage of this plant in traditional Malaysian medicine.
    Matched MeSH terms: Antimalarials/chemistry*
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