Synthesis, biological evaluation and docking studies of trans-stilbene methylthio derivatives as cytochromes P450 family 1 inhibitors
PBN-AR
Instytucja
Instytut Chemii Bioorganicznej Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Chemical Biology & Drug Design (25pkt w roku publikacji)
ISSN
1747-0277
EISSN
1747-0285
Wydawca
WILEY-BLACKWELL
DOI
URL
Rok publikacji
2017
Numer zeszytu
6
Strony od-do
1226-1236
Numer tomu
90
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
en
cytochromes P450 family 1
molecular docking
trans-resveratrol analogues
Streszczenia
Język
en
Treść
Cytochromes P450 family 1 (CYP1) are responsible for the metabolism of procarcinogens, for example polycyclic aromatic hydrocarbons and aromatic and heterocyclic amines. The inhibition of CYP1 activity is examined in terms of chemoprevention and cancer chemotherapy. We designed and synthesized a series of trans-stilbene derivatives possessing a combination of methoxy and methylthio functional groups attached in different positions to the trans-stilbene skeleton. We determined the effects of synthesized compounds on the activities of human recombinant CYP1A1, CYP1A2 and CYP1B1 and, to explain the variation of inhibitory potency of methoxystilbene derivatives and their methylthio analogues, we employed computational analysis. The compounds were docked to CYP1A1, CYP1A2 and CYP1B1 binding sites with the use of Accelrys Discovery Studio 4.0 by the CDOCKER procedure. For CYP1A2 and CYP1B1, values of scoring functions correlated well with inhibitory potency of stilbene derivatives. All compounds were relatively poor inhibitors of CYP1A2 that possess the most narrow and flat enzyme cavity among CYP1s. For the most active CYP1A1 inhibitor, 2-methoxy-4-methylthio-trans-stilbene, a high number of molecular interactions was observed, although the interaction energies were not distinctive.
Inne
System-identifier
PX-5a27e83bd5dec453891d95be
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