Synthesis of two novel thioacridinic derivatives and comparison of their in vitro biological activities.
Two novel compounds, 3-amino-9-(diethylaminoethylthio) acridine and 9-diethylaminoethylthioacridine, were synthesized and characterized. They were shown to be cytotoxic against K562 and Raji cell lines. A concentration of 10(-5) M killed around 40% of the cells after 3 h time of incubation. Intercalation into DNA was more efficient when a protonated nitrogen was present in a side chain of the ring system. At the cytotoxic concentrations (10(-5) M, 10(-6) M), inhibition of nucleic acid synthesis in K562, Raji cell lines and human leukocytes has been shown. The results presented suggest that the cytotoxicity and the inhibition of nucleic acid synthesis of the two compounds studied are inversely related to their intercalating capability into the DNA helix.
Groupe d'Etudes et Recherches en Chimie Thérapeutique Organique et Physique, Faculté de Pharmacie, Marseille, France.
R
R
Mannani
J P
JP
Galy
D
D
Sharples
J
J
Barbe
Y
Y
Barra
D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000609:Aminoacridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D005454:Fluorescence Polarization; D006801:Humans; D007364:Intercalating Agents; D007700:Kinetics; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects; D013696:Temperature
D000166:Acridines; D000609:Aminoacridines; D007364:Intercalating Agents; C064451:9-diethylaminoethylthioacridine; C064450:3-amino-9-(diethylaminoethylthio)acridine; D012313:RNA; D004247:DNA