title: Steroid dimers-in vitro cytotoxic and antimicrobial activities.
abstract: The in vitro cytotoxic activity of previously synthesized steroid dimers with different spacer group (sulfide, trithiolane ring or phosphorotrithioate) and the substituent at C-17 position was tested for their possible effects against following human tumor cell lines: cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562) and two human breast cancer cell lines (MDA-MB-361 and MDA-MB-453). These compounds, applied at micromolar concentrations, exhibited cytotoxic activity of different intensity (compared with cisplatin as a control), modality and selectivity in these malignant cell lines. The best activity against all four cell cancer lines was exhibited by dimer-sulfides. All screened compounds exerted concentration-dependent cytotoxic activity against leukemia K562 cells. The compounds which exerted the most pronounced cytotoxic action exhibited notably higher cytotoxic activities against K562, HeLa and MDA-MB-453 cells in comparison to resting and PHA-stimulated PBMC, pointing to a significant selectivity in their antitumor actions. Examination of the mechanisms of cytotoxicity on leukemia K562 cells revealed pro-apoptotic action of each of the investigated compounds applied at concentrations 2IC50. The most prominent pro-apoptotic action was exhibited by dimer-sulfide of cholest-4-en-3-one. Furthermore, almost all of the tested compounds at IC50 concentrations induced G1 phase cell cycle arrest in K562 cells. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp Artemia salina, were evaluated. There was no antibacterial activity. The best antifungal activity was exhibited against Saccharomyces cerevisiae by dimers linked with trithiolane ring, indicating a selective activity of investigated compounds.
authors.affiliation: Center for Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, P.O. Box 473, 11001 Belgrade, Serbia. Electronic address: nkrstic@chem.bg.ac.rs.
authors.forename: Natalija M
authors.initials: NM
authors.lastname: Krstić
authors.affiliation: Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia. Electronic address: ivanamatic@sbb.rs.
authors.forename: Ivana Z
authors.initials: IZ
authors.lastname: Matić
authors.affiliation: Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia. Electronic address: juranicz@ncrc.ac.rs.
authors.forename: Zorica D
authors.initials: ZD
authors.lastname: Juranić
authors.affiliation: Center for Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, P.O. Box 473, 11001 Belgrade, Serbia. Electronic address: irenan2003@yahoo.com.
authors.forename: Irena T
authors.initials: IT
authors.lastname: Novaković
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, P.O. Box 158, 11001 Belgrade, Serbia. Electronic address: dsladic@chem.bg.ac.rs.
authors.forename: Dušan M
authors.initials: DM
authors.lastname: Sladić
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001156:Artemia / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000890:Anti-Infective Agents; D013256:Steroids
keywords: Antimicrobial activity; Caspase; Cell cycle analysis; Cell death; Cytotoxic activity; Steroid dimers