Modeling of purine derivatives transport across cell membranes based on their partition coefficient determination and quantum chemical calculations.
Mercaptopurine (6-MP), thioguanine (6-TG), and azathioprine (AZA) are purine antimetabolites introduced as anticancer or immunosuppressive drugs decades ago. Methylated AZA, called MAZA, is among the investigational drugs. The present study compares MAZA to the widely recognized drugs AZA, 6-MP, and 6-TG with respect to the ability of being transported across cell membranes. The obtained octanol/water phases partition coefficients and results of quantum chemical calculations predict the following sequence of hydrophobicity: MAZA > AZA > 6-TG > 6-MP.
Quantum Chemistry Group, Faculty of Chemistry, A. Mickiewicz University, 6 Grunwaldzka Street, 60-780 Poznań, Poland. hoffmann@man.poznan.pl
Marcin
M
Hoffmann
Maria
M
Chrzanowska
Tadeusz
T
Hermann
Jacek
J
Rychlewski
D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D001379:Azathioprine / Q000737:chemistry / Q000493:pharmacokinetics; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D015122:Mercaptopurine / Q000737:chemistry / Q000493:pharmacokinetics; D011687:Purines / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013866:Thioguanine / Q000737:chemistry / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D011687:Purines; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine