Synthesis and preliminary screening for the biological activity of some steroidal Δ 4 -unsaturated semicarbazone derivatives

• Published in: Steroids Vol. 148; p. 36
• Main Authors: Živković, Marijana B, Novaković, Irena T, Matić, Ivana Z, Sladić, Dušan M, Krstić, Natalija M
• Format: Journal Article
• Language: English
• Published: United States 01-08-2019
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Artemia - drug effects; Aspergillus - drug effects; Cell Proliferation - drug effects; Clostridium - drug effects; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Jurkat Cells; K562 Cells; Microbial Sensitivity Tests; Molecular Conformation; Pseudomonas aeruginosa - drug effects; Semicarbazones - chemical synthesis; Semicarbazones - chemistry; Semicarbazones - pharmacology; Stereoisomerism; Steroids - chemical synthesis; Steroids - chemistry; Steroids - pharmacology; Structure-Activity Relationship; 3-Oxo-α,β-unsaturated steroids; Carbazate esters; Semicarbazones; Biological activity
• ISSN: 1878-5867

Eleven new steroidal mono- and bis(semicarbazones) 2a-e, 4d and 3a-e have been prepared starting from various 3-oxo-α,β-unsaturated steroids. Mono-semicarbazones 2a-e were further subjected to ethyl chloroacetate in boiling absolute ethanol but, instead of expected intramolecular cyclocondensation reaction products, the new carbazate esters 5a-e were obtained. The structures of all synthesized compounds and identification of each E/Z isomer were deduced by elemental analysis, HRMS, NMR, and IR spectroscopy. Preliminary screening for the cytotoxic activity in vitro of the new compounds has been conducted against three cancer cell lines, K562, Jurkat and HeLa cells. HeLa cells were the most sensitive while K562 cells were the least sensitive to the cytotoxic action of the novel steroid derivatives. Compounds 2e, 3c and 5e were found to have the best but still moderate cytotoxic effects. All tested compounds showed very weak antimicrobial activities. These results demonstrate that the replacement of thioxo group with carbonyl group in steroidal hydrazone derivatives resulted in decrease in their biological activity.