New camptothecin derivatives for generalized oncological chemotherapy: Synthesis, stereochemistry and biology.
Derivatives of SN38 were synthesized that were either monosubstituted at C-5 or C-9 or disubstituted at both C-5 and C-9. Substitution to C-5 led to the generation of pairs of diastereomers (2c-2 h) in a one-pot reaction and was readily separable by HPLC. The absolute configurations of C-5 were established by electronic circular dichroism experiments. Compounds were tested in vitro against human cancer cell lines as well as a normal cell line. The impact of compounds 2a-2j on cancer cells is significant and the IC50 values against the normal cell line are several times higher than that of SN38. Using the Mannich reaction we obtained a new innovative group of derivatives with unique biological properties that preserves the high cytotoxicity in cancer cells and eliminates the acute toxicity to non-neoplastic cells, which can be considered a breakthrough in chemotherapy with the use of topoisomerase I inhibitors from the camptothecin family.
['Naumczuk|Beata|B|', 'Górecki|Marcin|M|', 'Wiktorska|Katarzyna|K|', 'Urbanowicz|Magdalena|M|', 'Sitkowski|Jerzy|J|', 'Lubelska|Katarzyna|K|', 'Milczarek|Małgorzata|M|', 'Bednarek|Elżbieta|E|', 'Bocian|Wojciech|W|', 'Kozerski|Lech|L|']
Synthesis Biological activity ECD spectroscopy SN38 derivatives