A study of conformational states of substrates of isoform 3A4 of cytochrome P450

Grishina, Maria; Потемкин, В. А.; Pogrebnoi, A. A.; Ivshina, N. N.

doi:10.1134/s0006350908050060

Cited by 2 publications

(1 citation statement)

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“…It is shown that the compounds with podand chains in their composition undergo metabolism by cytochrome P450 isoform 3A4. Also using the CiS algorithm to predict the probability of metabolism of pyrimidine derivatives, the quantitative model relating the probability of metabolism of substrates of isoform 3A4 to their structural parameters has previously been developed [17,18].…”

Section: Mechanism Of Action Of Drugs With Podand Chainsmentioning

confidence: 99%

Effect of the structural characteristics of dihydrofolate reductase inhibitors on their metabolic properties

et al. 2012

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The orientation of dihydropyrimidine derivatives containing podand chains is determined in the model receptor using the CiS algorithm. The orientation of compounds with podand chains is compared with the location of compounds without podand chains in the model receptor. The pharmacophore and antipharmacophore parts of the compounds are analyzed. Amino acid residues responsible for the effective interactions of the compounds with podand chains with the binding site of dihydrofolate reductase (DHFR) are identified using the X-ray diffraction data. The mechanism of the action of tuberculostatic compounds with podand chains in their composition is proposed, which assumes the studied molecules to undergo metabolism by cytochrome P450 isoform 3A4 forming metabolites. The most active are the metabolites without the fragments of podand chains, which interact with DHFR. Therefore, the compounds containing podand chains are prodrugs.

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Section: Mechanism Of Action Of Drugs With Podand Chainsmentioning

confidence: 99%