Cytotoxic action of conjugates of alpha-fetoprotein and epidermal growth factor with photoheme, chlorines, and phthalocyanines.
Covalently bound conjugates of alpha-fetoprotein (AFP) and epidermal growth factor (EGF) with photoheme (PH), 3-desvinyl-3-formylchlorine p6 (Chl p6), chlorine e6 (Chl e6), aluminum disulfochloride phthalocyanine (PC(Al)), and cobalt octa-4,5-carboxyphthalocyanine (teraphthal, TP(Co)) were synthesized. Their molar ratios were 1:4 for AFP-cytotoxin conjugates (cf. 1:10 for AFP-TP(Co)) and 1:2 for EGF conjugates (cf. 1:1 for EGF-PC(Al)). Dark toxicity of both protein conjugates with PH, chlorines, and PC(Al) was much lower than their phototoxicity. Studies on phototoxicity demonstrated that PC(Al) conjugates with AFP and EGF and also EGF-Chl p6 were the most effective. The cytotoxic activity (CTA) of AFP-PC(Al) and EGF-Chl p6 was 80% and of EGF-PC(Al) 64% higher than the CTA of the free drugs. Conjugates with TP(Co) were much more toxic on their activation with ascorbic acid (AA): in the presence of AA the CTA of AFP-TP(Co) and of EGF-TP(Co) was 19 and 61.1% higher, respectively, than the CTA of the free TP(Co).
Savitsky
A A
AA
Moscow Research Institute of Medical Ecology, Moscow, 113149, Russia. sergsev@aha.ru
Gukasova
N V
NV
Gumanov
S G
SG
Feldman
N B
NB
Luk'yanets
E A
EA
Mironov
A F
AF
Yakubovskaya
R I
RI
Lutsenko
S V
SV
Severin
S E
SE
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002713:Chlorine / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D006418:Heme / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry; D054833:Isoindoles; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D000509:alpha-Fetoproteins; D006418:Heme; D002713:Chlorine; D004815:Epidermal Growth Factor; C013647:phthalocyanine