Synthesis of some steroidal oximes, lactams, thiolactams and their antitumor activities

• Published in: Steroids Vol. 72; no. 5; pp. 406 - 414
• Main Authors: Krstic, Natalija M., Bjelakovic, Mira S., Zizak, Zeljko, Pavlovic, Mirjana D., Juranic, Zorica D., Pavlovic, Vladimir D.
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 01.05.2007; Elsevier; Elsevier Science
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Apoptosis - drug effects; Biochemistry & Molecular Biology; Biological and medical sciences; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Endocrinology & Metabolism; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; K562 Cells; Lactams - chemical synthesis; Lactams - chemistry; Lactams - pharmacology; Leukocytes, Mononuclear - metabolism; Life Sciences & Biomedicine; Oximes - chemical synthesis; Oximes - chemistry; Oximes - pharmacology; Science & Technology; Steroidal lactams; Steroidal oximes; Steroidal thiolactams; Steroids - chemical synthesis; Steroids - chemistry; Steroids - pharmacology; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacology; Vertebrates: endocrinology; Steroidal thiolactams; Steroidal lactams; Steroidal oximes; Antiproliferative activity; AUTOANTIBODIES; APOPTOSIS; steroidal thiolactams; ANALOGS; antiproliferative activity; steroidal oximes; steroidal lactams; CELL-DEATH; 5-ALPHA-REDUCTASE; 19-NOR-10-AZASTEROIDS; PATHWAY; 5 ALPHA-REDUCTASE; INHIBITORS; Antineoplastic agent; Biosynthesis
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2007.02.005

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.