Interaction with serum albumin as a factor of the photodynamic efficacy of novel bacteriopurpurinimide derivatives.
Optimization of the chemical structure of antitumor photosensitizers (PSs) is aimed at increasing their affinity to a transport protein, albumin and irreversible light-induced tumor cell damage. Bacteriopurpurinimide derivatives are promising PSs thanks to their ability to absorb light in the near infrared spectral region. Using spectrophotometry, we show that two new bacteriopurpurinimide derivatives with different substituents at the N atoms of the imide exocycle and the pyrrole ring A are capable of forming non-covalent complexes with human serum albumin (HSA). The association constant (calculated with the Benesi-Hildebrand equation) for N-ethoxybacteriopurpurinimide ethyloxime (compound 1) is higher than that for the methyl ether of methoxybacteriopurpurinimide (compound 2) (1.18×10(5) M-1 vs. 1.26×10(4) M(-1), respectively). Molecular modeling provides details of the atomic interactions between 1 and 2 and amino acid residues in the FA1 binding site of HSA. The ethoxy group stabilizes the position of 1 within this site due to hydrophobic interaction with the protein. The higher affinity of 1 for HSA makes this compound more potent than 2 in photodynamic therapy for cultured human colon carcinoma cells. Photoactivation of 1 and 2 in cells induces rapid (within a few minutes of irradiation) necrosis. This mechanism of cell death may be efficient for eliminating tumors resistant to other therapies.
N.M. Emanuel Institute of Biochemical Physics, Kosygina Str., 4, Moscow, 119334, Russia.
Akimova
A
Akimova
Petersburg Nuclear Physics Institute, Orlova Roscha, Gatchina, Leningrad district, 188300, Russia ; St.Petersburg State Polytechnical University, Politekhnicheskaya Str., 29, St. Petersburg, 195251, Russia.
G N
GN
Rychkov
M.V. Lomonosov Moscow State University of Fine Chemical Technologies, Prospekt Vernadskogo, 86, Moscow, 119571, Russia.
M A
MA
Grin
N.N. Blokhin Russian Cancer Research Center, Kashirskoe Shosse, 24, Moscow, 115478, Russia.
N A
NA
Filippova
N.M. Emanuel Institute of Biochemical Physics, Kosygina Str., 4, Moscow, 119334, Russia.
G V
GV
Golovina
N.M. Emanuel Institute of Biochemical Physics, Kosygina Str., 4, Moscow, 119334, Russia.
N A
NA
Durandin
N.M. Emanuel Institute of Biochemical Physics, Kosygina Str., 4, Moscow, 119334, Russia.
A M
AM
Vinogradov
Georgian Technical University, Kostava Str., 77, Tbilisi, 0175, Georgia.
T A
TA
Kokrashvili
M.V. Lomonosov Moscow State University of Fine Chemical Technologies, Prospekt Vernadskogo, 86, Moscow, 119571, Russia.
A F
AF
Mironov
N.N. Blokhin Russian Cancer Research Center, Kashirskoe Shosse, 24, Moscow, 115478, Russia.
A A
AA
Shtil
N.M. Emanuel Institute of Biochemical Physics, Kosygina Str., 4, Moscow, 119334, Russia.
V A
VA
Kuzmin
albumin; association constant; cancer; necrosis; photodynamic therapy; photosensitizers