Untitled

Потемкин, В. А.; Grishina, Maria; Belik, A. V.; Чупахин, О. Н.

doi:10.1023/a:1015744707357

Cited by 9 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The suggested approach is based on the combination of 4D/3D QSAR algorithms-BiS/MC (multiconformational) 1 [11][12][13][14] and ConGO (www.modelchem.ru) [14,15]. The first algorithm, BiS/MC, permits multiconformational study of biologically active compounds and selection of conformers responsible for the binding of a molecule with the receptor [e.g., [16][17][18] (Figs.…”

Section: Description Of the Paradigm Suggested For Pattern Recognitiomentioning

confidence: 99%

A new paradigm for pattern recognition of drugs

Потемкин

Grishina

2008

J Comput Aided Mol Des

View full text Add to dashboard Cite

A new paradigm is suggested for pattern recognition of drugs. The approach is based on the combined application of the 4D/3D quantitative structure-activity relationship (QSAR) algorithms BiS and ConGO. The first algorithm, BiS/MC (multiconformational), is used for the search for the conformers interacting with a receptor. The second algorithm, ConGO, has been suggested for the detailed study of the selected conformers' electron density and for the search for the electron structure fragments that determine the pharmacophore and antipharmacophore parts of the compounds. In this work we suggest using a new AlteQ method for the evaluation of the molecular electron density. AlteQ describes the experimental electron density (determined by low-temperature highly accurate X-ray analysis) much better than a number of quantum approaches. Herein this is shown using a comparison of the computed electron density with the results of highly accurate X-ray analysis. In the present study the desirability function is used for the first time for the analysis of the effects of the electron structure in the process of pattern recognition of active and inactive compounds. The suggested method for pattern recognition has been used for the investigation of various sets of compounds such as DNA-antimetabolites, fXa inhibitors, 5-HT(1A), and alpha(1)-AR receptors inhibitors. The pharmacophore and antipharmacophore fragments have been found in the electron structures of the compounds. It has been shown that the pattern recognition cross-validation quality for the datasets is unity.

show abstract

Section: Description Of the Paradigm Suggested For Pattern Recognitiomentioning

confidence: 99%

A new paradigm for pattern recognition of drugs

Потемкин

Grishina

2008

J Comput Aided Mol Des

View full text Add to dashboard Cite

show abstract

“…[5][6][7][8][9][10][11][12] On the other hand the Al 3ϩ ion forms the complexes of the highest stability with the ligands containing hard donor groups (i.e. basic negatively charged oxygen atoms).…”

Section: )mentioning

confidence: 99%

“…Thus, the reduced bio-availability of the quinolones in the presence of Al may be explained by chelation between Al 3ϩ ion and the 3-carboxyl and 4-oxo functional groups of the quinolones. [5][6][7][8][9][10][11][12] Besides the reduction of the bioavailability and activity of quinolones the interactions between aluminum ion and quinolones have significant effect on metabolism of aluminum in human organism. Numerous investigations have shown that aluminum can be regarded as detrimental and in particular neurotoxic element.…”

mentioning

confidence: 99%

“…4) To explain the observed phenomenon one may take into account that number of forms in which quinolones may exist in solution (neutral, cationic, zwitterionic and anionic) as well as vicinity of carbonyl and carboxyl groups make them the suitable ligands for hard acid metal ions, in particular for Al 3ϩ . [5][6][7][8][9][10][11][12] On the other hand the Al 3ϩ ion forms the complexes of the highest stability with the ligands containing hard donor groups (i.e. basic negatively charged oxygen atoms).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Solution Equilibria between Aluminum(III) Ion and some Fluoroquinolone Family Members. Spectroscopic and Potentiometric Study

Đjurdjević

Joksović

Jelić

et al. 2007

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Fluorinated quinolones are antibacterial agents which chemically, may be regarded as weak substituted heterocyclic amino acids. These drugs primarily find use in the treatment of urinary and respiratory infections. Fluoroquinolones exhibit strong activity against Gram-negative and some Gram-positive bacteria, though many anaerobic strains are resistant.1) Fleroxacin and moxifloxacin are fluoroquinolone family members which belong to 2nd and 4th generation of these drugs, respectively (Chart 1).In clinical practice often, fluoroquinolones are administered concomitantly with other drugs which may contain metal ions. The presence of metal ions from e.g. metal based antacids or multivitamin formulations may significantly affect the activity of quinolones since they can readily bind several divalent or trivalent metal ions.2) Complexation alters solubility, lypophilicity, antimicrobial activity and protein binding of quinolones. The solubility of all ionic quinolone complexes is much greater than that of molecular complexes which are only sparingly soluble.3) Some metal-quinolone complexes show antimicrobial activity comparable to that or free quinolone but in some cases the activity is increased or lowered. Mg 2ϩ and Al 3ϩ were found to decrease the activity of quinolones whereas Fe 3ϩ and Zn 2ϩ complexes exhibit greater activity.2) Clinical investigations have shown that concomitant intake of fluoroquinolones and aluminum-containing antacids results in reduced maximal plasma concentration accompanied by the decrease in AUC. Both effects lead to the decreased bioavailability of the drug, down to 40%. 4)To explain the observed phenomenon one may take into account that number of forms in which quinolones may exist in solution (neutral, cationic, zwitterionic and anionic) as well as vicinity of carbonyl and carboxyl groups make them the suitable ligands for hard acid metal ions, in particular for Al 3ϩ . [5][6][7][8][9][10][11][12] On the other hand the Al 3ϩ ion forms the complexes of the highest stability with the ligands containing hard donor groups (i.e. basic negatively charged oxygen atoms). Thus, the reduced bio-availability of the quinolones in the presence of Al may be explained by chelation between Al 3ϩ ion and the 3-carboxyl and 4-oxo functional groups of the quinolones. [5][6][7][8][9][10][11][12] Besides the reduction of the bioavailability and activity of quinolones the interactions between aluminum ion and quinolones have significant effect on metabolism of aluminum in human organism. Numerous investigations have shown that aluminum can be regarded as detrimental and in particular neurotoxic element.13) Patients with high tissue and serum level of aluminum may develop blood, bone or brain diseases which may be linked to the excess of aluminum.14)The presence of fluoroquinolones may influence Al absorption through the formation of Al-complexes which may be stable enough to produce a sufficient decrease in free Al 3ϩ concentration so that a significant amount of the poorly solu-

show abstract

“…Hence, to solve the problem of molecular orientation within a receptor cavity, it is necessary to determine the cumulative field for an ensemble of molecules. This problem can be solved with 3D QSAR algorithm BiS [13][14][15][16][17]. The applicability of this algorithm to the analysis of biological activity was earlier tested on a substantial amount of ensembles of compounds.…”

Section: Introductionmentioning

confidence: 99%

Modeling of drug molecule orientation within a receptor cavity in the BiS algorithm framework

2007

Self Cite

View full text Add to dashboard Cite

The BiS algorithm is suggested for modeling the drug molecule orientation within a receptor cavity. It is based on the assumption of complementarity of the field created by biologically active compounds and the field of the responsive receptor. The comparison of predicted orientations of various biologically active compounds on the relevant receptors with the data of X-ray structural studies (Protein Data Bank) reveals that the results obtained with this approach surpasses those reported in the literature. The suggested technique made it possible to elucidate the details of the action mechanism of DNA antimetabolites, dihydrofolate reductase inhibitors. The dependence of the activity on the structural parameters of "ligandreceptor" complexes is determined.

show abstract

Untitled

Cited by 9 publications

References 0 publications

A new paradigm for pattern recognition of drugs

A new paradigm for pattern recognition of drugs

Solution Equilibria between Aluminum(III) Ion and some Fluoroquinolone Family Members. Spectroscopic and Potentiometric Study

Modeling of drug molecule orientation within a receptor cavity in the BiS algorithm framework

Contact Info

Product

Resources

About