In vitro testing of cyto- and genotoxicity of new porphyrin water-soluble metal derivatives.
Porphyrins and porphyrin derivatives have an outstanding potential for discovery of novel pharmacological agents due to their ability for numerous chemical modifications and a variety of mechanisms of biological effects. New water-soluble Ag and Zn derivatives of tetrachloride meso-tetra (4-N-oxiethylpyridyl) porphyne were synthesized. Cyto- and genotoxicity of these substances were tested in vitro by the vital dye (trypan blue) exclusion and the micronucleus tests, respectively. Both metalloporphyrins were shown to be cytotoxic for Cos-7 (fibroblast-like African green monkey kidney cells transformed by simian virus 40 [SV40]), DU 145 (epithelial-like cells of human prostate carcinoma), and K-562 (human chronic myeloid leukemia cells) cell lines. At the same time they did not cause chromosome fragmentation in K-562 cell line at as high concentrations as IC(50) (20 micromol/L for Ag and 70 micromol/L for Zn derivative). Thus, the metalloporphyrins tested meet at least two important demands to potential anticancer drugs as they combine the cytotoxicity with low genotoxicity. The three in vitro tumor models used are relevant to further in vitro and in vivo preclinical investigation of the studied metalloporphyrins as potential chemotherapeutics.
Gasparyan
Gennadi
G
Department of Genetics and Cytology, Yerevan State University, Yerevan, Armenia. gena@ysu.am
Hovhannisyan
Galina
G
Ghazaryan
Robert
R
Sahakyan
Lida
L
Tovmasyan
Artak
A
Grigoryan
Rusanna
R
Sarkissyan
Natalia
N
Haroutiunian
Samvel
S
Aroutiounian
Rouben
R
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D020014:K562 Cells; D008665:Metalloporphyrins / Q000633:toxicity*; D015162:Micronucleus Tests; D012995:Solubility; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D014867:Water