Synthesis of some steroidal oximes, lactams, thiolactams and their antitumor activities.
The antiproliferative activity of previously synthesized (Z)-cholest-4-en-6-one oxime (1), (E)-cholest-4-en-6-one oxime (2), 7-aza-B-homocholest-4-en-6-one (3) and 6-aza-B-homocholest-4-en-7-one (4) and newly synthesized 6-thioxo-7-aza-B-homocholest-4-ene (5) and 6-aza-7-thioxo-B-homocholest-4-ene (6) was tested for their possible effects against two human tumor cell lines, cervical carcinoma (HeLa) and chronic myelogenous leukemia (K-562). Compounds 1-6, exerted a dose-dependent antiproliferative effect toward cell lines used in experimental design, showing high selectivity in their action for tumor cells in comparison to normal immunocompetent cells (non-stimulated PBMC and PHA-stimulated PBMC). Compounds 2, 3 and 4 exhibited a very high but selective antitumor activity, by inducing apoptosis in sensitive, for that purpose targeted tumor cell line (HeLa cells). Low toxic effect upon both non-stimulated, and PHA stimulated PBMCs from control, healthy volunteers, has been detected for compounds 1, 2, 3 and 4. The possible reasons for profound differences in the effects of this spectrum of steroidal compounds between tumor cell lines and normal stimulated and non-stimulated PBMCs are discussed. The molecular mechanisms for apoptotic events in HeLa cell line are suggested. The guidelines for further research are underlined.
Krstić
Natalija M
NM
Center for Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, P.O. Box 473, 11001 Belgrade, Serbia. nkrstic@chem.bg.ac.yu
Bjelaković
Mira S
MS
Zizak
Zeljko
Z
Pavlović
Mirjana D
MD
Juranić
Zorica D
ZD
Pavlović
Vladimir D
VD
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D007769:Lactams; D010091:Oximes; D013256:Steroids; D013438:Sulfhydryl Compounds