An in silico evaluation of the ADMET profile of the StreptomeDB database

Ntie‐Kang, Fidele

doi:10.1186/2193-1801-2-353

Cited by 140 publications

(64 citation statements)

References 45 publications

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“…Sketching of the 3D structures of the compounds was done using the builder module of the MOE software (CCG, Montreal). Energy minimisation was subsequently carried out using a previously described protocol [35–39], using the MMFF94 forcefield [40], reaching a gradient of 0.01 kcal/mol. The energy minimized structures were then saved (in mol2 format).…”

Section: Experimental Pharmacokinetic Profilingmentioning

confidence: 99%

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Nyongbela¹,

Ntie‐Kang²,

Hoye³

et al. 2017

Nat. Prod. Bioprospect.

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The antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1–6), isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is reported. The study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The in silico method employed a total of 46 descriptors, calculated using Schrödinger QikProp software. 18 of these molecular descriptors that are often used to predict DMPK profiles of drug-like molecules have been selected for discussion. In vitro experimental assessment of metabolic stability made use of human liver microsomes, which was used to correlate theoretical predictions with experimental findings. Overall, the test compounds have been found to have acceptable physicochemical properties and fall within the ranges associated with “drug-like” molecules. Moreover, the compounds exhibited minimal degradation in incubations with human liver microsomes. Although some of these compounds have been reported previously (1, 2, 4 and 5), this is the first report on their antiparasitic activities, as well as assessment of their DMPK profiles. These results have therefore provided a window for further development of this novel class of sesquiterpene molecules as potential antiparasitic drugs.Graphical Abstract Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-017-0125-y) contains supplementary material, which is available to authorized users.

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Section: Experimental Pharmacokinetic Profilingmentioning

confidence: 99%

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Nyongbela¹,

Ntie‐Kang²,

Hoye³

et al. 2017

Nat. Prod. Bioprospect.

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“…and Ph.D. theses and online databases. 54,75 The information gathered is discussed under the main compound classes, as presented below and summarised in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Compounds from African Medicinal Plants with Activities against Protozoal Diseases: Schistosomiasis, Trypanosomiasis and Leishmaniasis

Cv¹,

Ntie‐Kang²,

Sh.³

et al. 2018

Preprint

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An absolute configuration of 5R seems to decrease activity of the compound IntroductionProtozoa may be considered as microscopic, essentially single-celled, eukaryotic organisms that are free-living or parasitic (obtaining their food by eating other organisms or their products) in nature. Parasitic protozoal diseases continue to be a cause of considerable morbidity and mortality globally. 1,2Parasitic protozoal diseases include malaria, 3,4 trypanosomiasis (African sleeping sickness and Chagas disease), 5-7 leishmaniasis 8 and schistosomiasis. 9,10 They threaten almost one-third of the world's population, the most numerous incidents being recorded in over 100 Tropical and developing countries and territories, Figure 1. 11,12 Malaria, for example, was reported by the WHO, to be responsible for approximately 214 million sickness cases and 438,000 deaths globally in 2017. 13 The African region recorded the most death-related cases, especially amongst infants below the age of 5 and pregnant women. Schistosomiasis, caused by parasites of the Schistosoma genus are responsible for about 200 million sickness cases and about 280,000 death-related incidents annually worldwide.9,10,14 Only one drug (praziquantel) has been proven to be effective in the treatment of human schistosomiasis, with no vaccine available or in development so far.15-21 Serious concerns about drug selectivity and resistance were raised in 2013 when over 30 million people were treated in Sub-Saharan Africa. 20 Moreover, observed resistance and reduced efficiency of praziquantel in laboratory strains have prompted the search for alternative therapeutic strategies. Trypanosomiasis, which represents several diseases caused by parasites of the genus Trypanosoma, is also of interest. 5,27,29 This disease, which is much arguably the most important disease of man and domesticated animals, accounts for over 8 million reported annual cases globally, especially in the tropical regions of Latin America and Africa. 30,31 Although the present number of cases seems negligible on a worldwide scale, great socioeconomic effects on the endemic areas by this disease are forecast if inadequate attention (both at the communal, national, and international levels) is not given. 7,29,[32][33][34] Leishmaniasis is caused by parasites of the Leishmania type, which is also transmitted by certain types of sandflies. 35,36 The diseases are reported by the WHO to be responsible for about 1 million new cases leading to approximately 30,000 deaths annually on a global scale. The major cause is linked to environmental changes A R T I C L E I N F O A B S T R A C TArticle history:English abstract: Parasitic diseases continue represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug di...

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“…The Lipinski rule of five was further used to evaluate lipophilicity and water solubility, the rule requires that, for a compound to have good lipophilicity it should have no more than 5 MlogP value (MlogP ≤ 5). The predicated BBB filter indicated low for all derivatives suggesting that they may not permeate to the brain and thus not causing damage to the central nervous system, the computed log BB fell with the recommended range (−3 to 1) for log BB [37]. Oral bioavailability was predicated by using Madin-Darby canine kidney (MDCK) cell permeability, the recommended range for MDCK is <25 poor and >500 great.…”

Section: Pharmacokinetic (Admet) Analysismentioning

confidence: 99%

Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes

Shadrack¹,

Ndesendo²

2017

CMB

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Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, Cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.

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An in silico evaluation of the ADMET profile of the StreptomeDB database

Cited by 140 publications

References 45 publications

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Compounds from African Medicinal Plants with Activities against Protozoal Diseases: Schistosomiasis, Trypanosomiasis and Leishmaniasis

Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes

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