ChemInform Abstract: CONFORMATION OF 7‐CHLORO‐5‐PHENYL‐D5‐3(S)‐METHYLDIHYDRO‐1,4‐BENZODIAZEPIN‐2‐ONE IN SOLUTION

Šunjić, Vitomir; Lisini, A.; Sega, Alessandro; KOVAC, T.; Kajfež, F.; Ruščić, Branko

doi:10.1002/chin.197949076

Cited by 6 publications

(7 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3), in rapid exchange between each other. The M conformer prevailed for chiral benzodiazepines 29 with the (S) absolute configuration at C3 of the seven-membered ring. Thus the M conformation prevailed when diazepam was bound to the albumins.…”

Section: Measurementsmentioning

confidence: 99%

Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Pistolozzi

Bertucci

2008

Chirality

View full text Add to dashboard Cite

Drug binding to albumins from different mammalian species was investigated to disclose evidence of species-dependent stereoselectivity in drug-binding processes and affinities. This aspect is important for evaluating the reliability of extrapolating distribution data among species. The circular dichroism (CD) signal induced by drug binding to the albumins [human serum albumin (HSA), bovine serum albumin (BSA), rat serum albumin (RSA), and dog serum albumin (DSA)] were measured and analyzed. The binding of selected drugs and metabolites to HSA significantly differed from the binding to the other albumins in terms of affinity and conformation of the bound ligands. In particular, phenylbutazone, a marker of site one on HSA, showed a higher affinity for binding to BSA with respect to RSA, HSA, and DSA, respectively. In the case of diazepam, a marker of site two on HSA, the affinity decreased in order from HSA to DSA, RSA, and BSA. The induced CD spectra were similar in terms of energy and band signs, suggesting almost the same conformation for the bound drug to the different albumins. Stereoselectivity was high for the binding of ketoprofen to HSA and RSA. A different sign was observed for the CD spectra induced by the drug to the two albumins because of the prevalence of a different conformation of the bound drug. Interestingly, the same induced CD spectra were obtained using either the racemic form or the (S)-enantiomer. Finally, significant differences were observed in the affinity of bilirubin, being highest for BSA, then decreasing for RSA, HSA, and DSA. A more complex conformational equilibrium was observed for bound bilirubin.

show abstract

Section: Measurementsmentioning

confidence: 99%

Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Pistolozzi

Bertucci

2008

Chirality

View full text Add to dashboard Cite

show abstract

“…21 In another study, it was proposed that the P-conformation is selectively adopted by the (R)-benzodiazepine enantiomers, while the Mconformation is preferred by the (S)-enantiomers. 35 The different types of binding interactions noted between benzodiazepine and ibuprofen enantiomers may reflect different populations for these agents at the various binding regions on HSA.…”

Section: Proposed Model For Ibuprofen -Benzodiazepinementioning

confidence: 99%

Chromatographic analysis of allosteric effects between ibuprofen and benzodiazepines on human serum albumin

2005

View full text Add to dashboard Cite

show abstract

“…5B), in fast exchange between each other, with the M conformer is related to the (S) absolute configuration at C3 of the heptaatomic ring of chiral benzodiazepines. 54 When bound to HSA, DZP is stabilized in its M conformation, as shown by Snatzke and coworkers in 1979. 55,56 Therefore, a well-defined induced CD spectrum is observed upon binding to the stereospecific site on HSA, closely resembling that of a chiral benzodiazepine (Fig.…”

Section: Spectroscopic Investigationmentioning

confidence: 88%

Drug binding to human serum albumin: Abridged review of results obtained with high‐performance liquid chromatography and circular dichroism

2006

View full text Add to dashboard Cite

The drug binding to plasma and tissue proteins are fundamental factors in determining the overall pharmacological activity of a drug. Human serum albumin (HSA), together with a 1 -acid glycoprotein (AGP), are the most important plasma proteins, which act as drug carriers, with drug pharmacokinetic implications, resulting in important clinical impacts for drugs that have a relatively narrow therapeutic index. This review focuses on the combination of biochromatography and circular dichroism as an effective approach for the characterization of albumin binding sites and their enantioselectivity. Furthermore, their applications to the study of changes in the binding properties of the protein arising by the reversible or covalent binding of drugs are discussed, and examples of physiological relevance reported. Perspectives of these studies reside in supporting the development of new drugs, which require miniaturization to facilitate the screening of classes of compounds for their binding to the target protein, and a deeper characterization of the mechanisms involved in the molecular recognition processes.

show abstract

ChemInform Abstract: CONFORMATION OF 7‐CHLORO‐5‐PHENYL‐D5‐3(S)‐METHYLDIHYDRO‐1,4‐BENZODIAZEPIN‐2‐ONE IN SOLUTION

Cited by 6 publications

References 1 publication

Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Chromatographic analysis of allosteric effects between ibuprofen and benzodiazepines on human serum albumin

Drug binding to human serum albumin: Abridged review of results obtained with high‐performance liquid chromatography and circular dichroism

Contact Info

Product

Resources

About