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Prioritization of anti-malarial hits from nature: chemo-informatic profiling of natural products with in vitro antiplasmodial activities and currently registered anti-malarial drugs

, : Prioritization of anti-malarial hits from nature: chemo-informatic profiling of natural products with in vitro antiplasmodial activities and currently registered anti-malarial drugs. Malaria Journal 15(): 50-50

A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). Natural products with in vitro antiplasmodial activities (NAA) were compiled from various sources. These natural products were sub-divided into four groups based on inhibitory concentration (IC50). Key molecular descriptors and physicochemical properties were computed for these compounds and analysis of variance used to assess statistical significance amongst the sets of compounds. Molecular similarity analysis, estimation of drug-likeness, in silico pharmacokinetic profiling, and exploration of structure-activity landscape were also carried out on these sets of compounds. A total of 1040 natural products were selected and a total of 13 molecular descriptors were analysed. Significant differences were observed among the sub-groups of NAA and CRAD for at least 11 of the molecular descriptors, including number of hydrogen bond donors and acceptors, molecular weight, polar and hydrophobic surface areas, chiral centres, oxygen and nitrogen atoms, and shape index. The remaining molecular descriptors, including clogP, number of rotatable bonds and number of aromatic rings, did not show any significant difference when comparing the two compound sets. Molecular similarity and chemical space analysis identified natural products that were structurally diverse from CRAD. Prediction of the pharmacokinetic properties and drug-likeness of these natural products identified over 50% with desirable drug-like properties. Nearly 70% of all natural products were identified as potentially promiscuous compounds. Structure-activity landscape analysis highlighted compound pairs that form 'activity cliffs'. In all, prioritization strategies for the NAA were proposed. Chemo-informatic profiling of NAA and CRAD have produced a wealth of information that may guide decisions and facilitate anti-malarial drug development from natural products. Articulation of the information provided within an interactive data-mining environment led to a prioritized list of NAA.

PMID: 26823078

DOI: 10.1186/s12936-016-1087-y

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Kehler, M.D.; Hadjistavropoulos, H.D., 2008: Is health anxiety a significant problem for individuals with multiple sclerosis?. Although symptoms of anxiety and depression are often present in individuals with Multiple Sclerosis (MS), less is known about the role of health anxiety in this population. This study investigated the relationship between health anxiety and copin...

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Morimoto, Y.; Kubo, S.; Shuto, T.; Tanaka, H.; Hirohashi, K.; Yamamoto, T.; Yamada, R.; Kinoshita, H., 2002: Power Doppler ultrasonographic diagnosis of small hepatocellular carcinomas. Power Doppler ultrasonography can evaluate the hemodynamics of intrahepatic tumors. The ability of power Doppler ultrasonography to detect small hepatocellular carcinomas and estimate the differentiation of the tumor by the patterns of intranodula...

Lopez Carvajal, A.; Grijalva Contreras, L.; Valenzuela Ruiz, J.; Juarez Gonsalez, R.; Robles Contreras, F., 1996: Identification and quantification of damage to raisins by pest insects in northwestern Mexico. Hortscience 31(4): 678

Lewis, K.M.; Amatya, K.; Coffman, M.F.; Ollendick, T.H., 2015: Treating nighttime fears in young children with bibliotherapy: evaluating anxiety symptoms and monitoring behavior change. Children's nighttime fears are a normal part of child development and are transient for most children, but result in considerable distress for others. The present study evaluated a 4-week bibliotherapy intervention designed to treat young chi...

Hamann, B., 1972: Experiences with the "DANA-Super" intrauterine pessary in marital and sexual counseling at Berlin-Buch. Zentralblatt für Gynakologie 94(46): 1563-1568

Norton R.A.; Behan Pelletier V.M., 1991: Calcium carbonate and calcium oxalate as cuticular hardening agents in oribatid mites acari oribatida. Hardening of adult oribatid mite cuticle by the deposition of crystalline calcium salts is demonstrated by a combination of X-ray diffraction and X-ray dispersion methods, in conjunction with experimental acid decalcification. Calcite (calium carb...

Oswald; Bechhoefer; Libchaber; Lequeux, 1987: Pattern formation behind a moving cholesteric-smectic-A interface. Physical Review. A, General Physics 36(12): 5832-5838

Roark, R.C., 1932: A Digest of the Literature of Derris (Deguelia) Species used as Insecticides, 1747-1931. This is an extremely comprehensive literary review on the derris genus of plants and is composed from world-wide publications. After a short introduction, the bibliography is dealt with in alphabetical (author) order, each of the 456 titles being...

Clissold, G.K.; Metz, E.A., 1966: Evaluation--a tangible process. Nursing Outlook 14(3): 41-45