News Update on Antimalarial Research: Aug – 2019

Antimalarial drug resistance

Malaria, the foremost rife and most pernicious parasitic illness of humans, is calculable to kill between one and 2 million individuals, primarily youngsters, each year. Resistance has emerged to all or any categories of antiprotozoal medicine except the artemisinins and is accountable for a recent increase in malaria-related mortality, significantly in continent. The American state novo emergence of resistance may be prevented by the utilization of antimalarial combos. Artemisinin-derivative combos area unit significantly effective, since they act speedily and area unit well tolerated and extremely effective. Widespread use of those medicine may roll back protozoal infection. [1]

Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.

A rapid, semiautomated microdilution technique was developed for mensuration the activity of potential antimalarial drug medication against polite intraerythrocytic asexual  styles of the human Plasmodium vivax Plasmodium falciparum. Microtitration plates were wont to prepare serial dilutions of the compounds to be tested. Parasites, obtained from continuous stock cultures, were subcultured in these plates for forty two h. Inhibition of uptake of a radiolabeled macromolecule precursor by the parasites served because the indicator of antimalarial drug activity. Results of recurrent measurements of activity with antimalarial drug, quinine, and therefore the investigational new drug antimalarial drug incontestable  that the tactic is sensitive and precise. many further antimalarial drug medication and compounds of interest were tested in vitro, and therefore the results were in keeping with obtainable in vivo knowledge. the employment of P. falciparum isolates with far-famed status to antimalarial drug medication conjointly permissible analysis of the cross-resistance potential of every compound tested. The applications and expectations of this new check system among a drug development program are mentioned. [2]

Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs

A mevalonate-independent pathway of isoprenoid synthesis gift in Plasmodium falciparum was shown to represent an efficient target for therapy of protozoal infection. This pathway includes 1-deoxy-D-xylulose 5-phosphate (DOXP) as a key matter. The presence of 2 genes coding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid synthesis in P. falciparum depends on the DOXP pathway. This pathway is maybe situated within the apicoplast. The recombinant P. falciparumDOXP reductoisomerase was stifled by fosmidomycin and its spinoff, FR-900098. each medicine suppressed the in vitro growth of multidrug-resistant P. falciparum strains. when medical care with these medicine, mice infected with the gnawer protozoal infection parasiteP. vinckei were cured. [3]

Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy

Glucose is a necessary nutrient for Plasmodium falciparum and strong glycolytic activity is indicative of viable parasites. mistreatment nuclear magnetic resonance spectroscopic analysis, we have a tendency to show that P. falciparum infected erythrocytes consume ~20 times a lot of aldohexose, and trophozoites metabolise ~6 times a lot of aldohexose than ring stage parasites. The glycolytic activity, and thus parasite viability, are often measured at intervals a amount of 2 h to 5 h, mistreatment this technique. This facilitates antimalarial drug bioactivity screening on ring and sporozoan stage parasites, completely. we have a tendency to demonstrate this mistreatment potent and mechanistically distinct antimalarial drug compounds like antimalarial drug, atovaquone, cladosporin, DDD107498 and artemisinin. Our findings indicate that ring stage parasites are inherently a lot of tolerant to antimalarial drug inhibitors, a feature which can facilitate emergence of drug resistance. Thus, there’s a requirement to get novel antimalarial drug compounds, that are potent and quick acting against ring stage parasites. The nuclear magnetic resonance technique rumored here will facilitate the identification of such molecules. [4]

Assessment of Spectroscopic Interaction of Lamivudine/Metronidazole with Dihydroartemisinin – Piperaquine Antimalarial Tablet

In vitro interactions between dihydroartemisinin (DHA) or piperaquine (PQ) parts of antiprotozoal dihydroartemisinin-piperaquine (DP) with lamivudine/metronidazole were studied victimization Fourier rework infrared qualitative analysis (FTIR). One mg of either of 3TC or antiprotozoal was mixed with one mg of crushed and pulverised stateless person pill and therefore the admixture pelletized with twenty mg restrainer (KBr) powder. The pellets were scanned at a pair of mm/s over wavenumber region of 4000 to five hundred cm-1. The bond vibrations of DHA and PQ were in step with the reference literature values. 3TC shifted (C=O) bond stretching of DHA from 1735 to 1649 cm-1 and (O-H) stretching from 2926 to 2922 cm-1. The endoperoxide bond vibration was shifted from 875 to 866 cm-1. 3TC conjointly shifted the characteristic aromatic (C-H) bending of PQ from 775 to 796 cm-1. The aromatic and acyclic  (C-N) stretchings were shifted from 1367 to 1384 cm-1 and 1274 to 1278 cm-1, severally. antiprotozoal shifted the (C=O) stretching of DHA from 1735 to 1643 cm-1 and lactone (C-O-O-C) stretching from 875 to 883 cm-1. The (O-H) stretching was shifted from 2926 to 2935 cm-1. Piperaquine aromatic (C-H) bending was shifted from 775 to 727 cm-1 whereas aromatic (C-Cl) stretching vibration from 1145 to 1143 cm-1. The undulation spectra shifts caused by 3TC and antiprotozoal on the characteristic spectra vibration of DHA and PQ were adjudged insignificant. There was no in vitro interaction between lamivudine/metronidazole and therefore the actives of stateless person pill. The medicine might not cause any biopharmaceutical implications on co-administration with stateless person pill. [5]

Reference

[1] White, N.J., 2004. Antimalarial drug resistance. The Journal of clinical investigation, 113(8), pp.1084-1092. (Web Link)

[2] Desjardins, R.E., Canfield, C.J., Haynes, J.D. and Chulay, J.D., 1979. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrobial agents and chemotherapy, 16(6), pp.710-718. (Web Link)

[3] Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Türbachova, I., Eberl, M., Zeidler, J., Lichtenthaler, H.K. and Soldati, D., 1999. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science, 285(5433), pp.1573-1576. (Web Link)

[4] Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy

Rupali Shivapurkar, Tejashri Hingamire, Akshay S. Kulkarni, P. R. Rajamohanan, D. Srinivasa Reddy & Dhanasekaran Shanmugam

Scientific Reportsvolume 8, Article number: 18076 (2018) (Web Link)

[5] Awofisayo, S. O., Alphonsus Ifiok, F., Jonathan, N. A., Igwe, C. N. and Ojobor, P. D. (2018) “Assessment of Spectroscopic Interaction of Lamivudine/Metronidazole with Dihydroartemisinin – Piperaquine Antimalarial Tablet”, Journal of Advances in Medicine and Medical Research, 27(10), pp. 1-7. doi: 10.9734/JAMMR/2018/28517. (Web Link)

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