Erratum: Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors

Zhao, Yuan H.; Le, Joelle; Abraham, Michael H.; Hersey, Anne; Eddershaw, Peter; Luscombe, Chris; Butina, Darko; Beck, Gordon; Sherborne, Brad; Cooper, Ian; Platts, James Alexis

doi:10.1002/jps.10118

Cited by 9 publications

(6 citation statements)

References 221 publications

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“…Human Intestinal Absorption (HIA) and Caco-2 permeability are good indicators of drug absorbance in the intestines and Caco-2 monolayers respectively. Human Intestinal Absorption data are the sum of bioavailability and absorption evaluated from the ratio of excretion or cumulative excretion in urine, bile and feces [29]. The predicted percentages of intestinal absorption are excellent for all the compounds tested, with values above 97% in all cases.…”

Section: Physico-chemical and Absorption Properties Calculationsmentioning

confidence: 93%

Selenocyanates and diselenides: A new class of potent antileishmanial agents

Plano

Baquedano

Moreno-Mateos

et al. 2011

European Journal of Medicinal Chemistry

120

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Section: Physico-chemical and Absorption Properties Calculationsmentioning

confidence: 93%

Selenocyanates and diselenides: A new class of potent antileishmanial agents

Plano

Baquedano

Moreno-Mateos

et al. 2011

European Journal of Medicinal Chemistry

120

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“…Others have emphasized the importance of keeping hydrogen-bonding or polar surface area to a minimum. − In some cases, utilization of a specific transporter, which has structure−activity relationships of its own, is necessary . In addition to published models, several vendors offer computer programs for predicting permeability or bioavailability; for example, Cerius2, , Idea, Absolv, − QikProp, QMPRPlus, VolSurf, , and OraSpotter…”

Section: Introductionmentioning

confidence: 99%

A Bioavailability Score

2005

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Responding to a demonstrated need for scientists to forecast the permeability and bioavailability (F) properties of compounds before their purchase, synthesis, or advanced testing, we have developed a score that assigns the probability that a compound will have F > 10% in the rat. Neither the rule-of-five, log P, log D, nor the combination of the number of rotatable bonds and polar surface area successfully categorized compounds. Instead, different properties govern the bioavailability of compounds depending on their predominant charge at biological pH. The fraction of anions with >10% F falls from 85% if the polar surface area (PSA) is < or = 75 A(2), to 56% if 75 < PSA < 150 A(2), to 11% if PSA is > or = 150 A(2). On the other hand, whereas 55% of the neutral, zwitterionic, or cationic compounds that pass the rule-of-five have >10% F, only 17% of those that fail have > 10% F. This same categorization distinguishes compounds that are poorly permeable from those that are permeable in Caco-2 cells. Further validation is provided with human bioavailability values from the literature.

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“…A drug penetrates membranes through passive diffusion, active transport and paracellular transport (Knöpfel et al 2019 ) and various in silico tools are available to calculate percentage HIA as a sum of bioavailability and absorption. HIA is evaluated from the ratio of excretion or cumulative excretion in urine, bile and feces (Zhao et al 2002 ) and permeability of a compound to either Caco-2 cells or MDCK cells. MDCK cells predict oral drug absorption with high accuracy.…”

Section: Discussionmentioning

confidence: 99%

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models

et al. 2023

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The global spread of multi-drug resistant P. falciparum , P. vivax , and P. malariae strains and absence of long-term effective vaccine makes chemotherapy the mainstay of malaria control strategies in endemic settings. The Mossman’s assay and the Organization for Economic Co-operation and Development (OECD), 2001 guideline 423, were used to determine the cytotoxicity and acute oral toxicity of a novel hybrid drug, artesunate-3-Chloro-4(4-chlorophenoxy) aniline (ATSA), in vitro and in vivo, respectively. A modified Desjardins method was used to screen for antiplasmodial activity using P. falciparum (3D 7 and W 2 ) strains in vitro. The Peter’s 4-day suppressive tests (4DTs) was used to evaluate the in vivo antimalaria activity using P. berghei ANKA strain, lumefantrine resistant (LuR), and piperaquine resistant (PQR) P. berghei lines. In silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles was assayed using PreADMET online prediction tool. The reference drug in all experiments was artesunate (ATS). Statistical significance between ATSA’s activities in treated and control mice was evaluated by one-way analysis of variance (ANOVA). Results show that inhibitory concentrations-50 (IC 50 ) of ATSA is 11.47 ± 1.3 (3D 7 ) and 1.45 ± 0.26 (W 2 ) against 4.66 ± 0.93 (3D 7 ) and 0.60 ± 0.15 (W 2 ) ng/ml of ATS with a selective index of 2180.91(3D 7 ) and a therapeutic index (TI) of > 71). No mortalities were observed in acute oral toxicity assays and mean weight differences for test and controls were statistically insignificant ( P > 0.05). The in vivo activity of ATSA was above 40% with effective dosage-50 (ED 50 ) of 4.211, 2.601, and 3.875 mg/kg body weight against P. berghei ANKA , LuR, and PQR lines, respectively. The difference between treated and control mice was statistically significant ( P < 0.05). ATSA has high intestinal absorption (HIA) > 95% and has medium human ether-a-go-go related gene (hERG) K + channel inhibition risks. Preclinical and clinical studies on ATSA are recommended to evaluate its value in developing novel drugs for future management of multi-drug resistant malaria parasites.

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Erratum: Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors

Cited by 9 publications

References 221 publications

Selenocyanates and diselenides: A new class of potent antileishmanial agents

Selenocyanates and diselenides: A new class of potent antileishmanial agents

A Bioavailability Score

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models

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