Atomic physicochemical parameters for three dimensional structure directed quantitative structure‐activity relationships III: Modeling hydrophobic interactions

Ghose, Arup K.; Pritchett, Avis; Crippen, Gordon M.

doi:10.1002/jcc.540090111

Cited by 458 publications

(311 citation statements)

References 12 publications

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“…In this initial evaluation, CYS and SMB were chosen as the most effective antioxidants. These results were confirmed by the values of cLogP calculated by molecular modeling using the method of Ghose-PritchettCrippen (Ghose, Pritchett, Crippen, 1988) showing the influence of lipid solubility on antioxidant activity.…”

Section: Molecular Modeling Studiessupporting

confidence: 65%

See 1 more Smart Citation

Rational use of antioxidants in solid oral pharmaceutical preparations

Celestino

Magalhães

Fraga

et al. 2012

Braz. J. Pharm. Sci.

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Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.Uniterms: Antioxidants/rational use. Excipients/evaluation. Butylated hydroxyanisole/rational use. Butylated hydroxytoluene/rational use. Sodium metabisulfite/rational use. Propyl gallate/rational use. Cysteine/rational use. Simvastatin/tablets/evaluation. Ketoconazole/tablets/evaluation. Atualmente, antioxidantes são usados como excipientes eficientes, que retardam ou inibem o processo de oxidação de moléculas. Excipientes são frequentemente associados a efeitos adversos. Estudos de estabilidade podem ajudar na busca por possíveis soluções para minimizar ou retardar os processos de degradação. A habilidade de prever as reações de oxidação em diferentes fármacos é importante. O estudo foi conduzido com o objetivo de avaliar o uso racional de hidroxianisol butilado (BHA), hidroxitolueno butilado (BHT), metabissulfito sódico (SMB), galato de propila (PG) e cisteína (CYS) em formulações de comprimidos de sinvastatina e cetoconazol. Eles foram avaliados por parâmetros de estabilidade e pela relação entre a eficiência dos antioxidantes e a estrutura química do fármaco. Os resultados foram comparados com testes de DPPH e simulações em computador. BHT f...

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Section: Molecular Modeling Studiessupporting

confidence: 65%

“…The effects of hydrogen bonds between methanol or other polar protic solvent and phenolic antioxidants can also lead to a reduction in their activity (Ghose, Pritchett, Crippen, 1988). In this initial evaluation, CYS and SMB were chosen as the most effective antioxidants.…”

Section: Molecular Modeling Studiesmentioning

confidence: 99%

Rational use of antioxidants in solid oral pharmaceutical preparations

Celestino

Magalhães

Fraga

et al. 2012

Braz. J. Pharm. Sci.

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“…In a previous paper (Lomba et al 2013;Lomba et al 2011) values of the logarithm of 1-octanol/water partition coefficient, log P, were computed in silico using the ALOGP method (Ghose and Crippen 1986;Ghose et al 1988;Viswanadhan et al 1989) with values of -0.14 for LA, -0.17 for ML, 0.38 for EL and 1.36 for BL. We have compared the computed log P values to those predicted with the KowWin method (available on http://esc.syrres.com/esc/est_kowdemo.htm) (Meylan and Howard 1995).…”

Section: Physico-chemical Properties Of Levulinates Related To Toxicitymentioning

confidence: 99%

Ecotoxicity studies of the levulinate ester series

et al. 2014

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Abstract:The increasing interest in the development of novel green solvents has led to the synthesis of benign alternative products with minimized environmental impacts.However, most of published studies on green solvents focus primarily on their physicochemical properties, with limited emphasis on absence of ecotoxicological assessment. In this study, we evaluated the acute ecotoxicity of four levulinates (levulinic acid, methyl levulinate, ethyl levulinate and butyl levulinate) on freshwater algae (Chlamydomonas reinhardtii), bacteria (Vibrio fischeri), daphnids (Daphnia magna) and earthworms (Eisenia foetida) using various dose-response tests. As a general trend, the toxicity of levulinate esters in aquatic exposure (assessed as the EC 50 ) increased as a function of increasing alkyl chain length; accordingly, the most toxic compound for the aquatic organisms was butyl levulinate, followed by ethyl levulinate and methyl levulinate. The most toxic compound for Eisenia foetida (terrestrial exposure) was methyl levulinate, followed by ethyl levulinate, butyl levulinate and levulinic acid; in this case, we observed an inverse relationship between toxicity and alkyl chain length. Based on both the lowest EC 50 found in the aquatic media and the ratio between predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC), we have estimated the maximum allowable values in the 2 environment for these chemicals to be 1.093 mg L -1 for levulinic acid, 2.761 mg L -1 for methyl levulinate, 0.982 mg L -1 for ethyl levulinate and 0.151 mg L -1 for butyl levulinate.

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“…Some properties of the solvents are reported in Table 1. The octanol/water partition coefficient (Ghose et al 1988), viz. the ratio of the concentrations of the solvent in octanol and water equilibrated phases, increases for decreased polarity of the solvent.…”

Section: Dehydration By Organic Solvents and Dimension Changes Measurmentioning

confidence: 99%

Solvent Polarity and Internal Stresses Control the Swelling Behaviour of Green Wood During Dehydration in Organic Solution

Chang¹,

Quignard²,

Renzo³

et al. 2012

BioResources

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The dimensional variations of green wood samples induced by organic solvents have been studied. The solvents used (ethanol, isopropanol, acetone, and acetonitrile) covered a wide range of polarity and were studied pure and in aqueous solutions over a wide range of concentrations. Samples of normal and tension wood of poplar were used in order to minimize the effect of hydrophobic extractives on the wood-solvent interactions. The evolution of wood volume and of tangential strain with the concentration of the organic solvents shows a behavior similar to gels, with a significant swelling for solutions of intermediate polarity. The similarity of volume obtained in water and less polar pure organic solvents strikingly contrasted the different effects of water and organic solvents on dry wood. Low-polarity solvents were extremely effective in the stress release of tension wood, as indicated by the pattern of longitudinal shrinkage. Solvent exchange does not affect the mesoporous structure of the cell walls of tension wood and is a promising way to reduce internal stress in wood products.

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Atomic physicochemical parameters for three dimensional structure directed quantitative structure‐activity relationships III: Modeling hydrophobic interactions

Cited by 458 publications

References 12 publications

Rational use of antioxidants in solid oral pharmaceutical preparations

Rational use of antioxidants in solid oral pharmaceutical preparations

Ecotoxicity studies of the levulinate ester series

Solvent Polarity and Internal Stresses Control the Swelling Behaviour of Green Wood During Dehydration in Organic Solution

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