title: New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities.
abstract: The reactions of 17α-hydroxyprogesterone with Lawesson's reagent (LR) in toluene, CH(2)Cl(2) and/or CCl(4) gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D (1)H-(13)C spectra (HSQC and HMBC) and homonuclear 2D spectra (NOESY) enabled complete (1)H and (13)C assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-453 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia salina, were evaluated. All tested compounds showed strong antifungal activity.
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. nkrstic@chem.bg.ac.rs
authors.forename: Natalija M
authors.initials: NM
authors.lastname: Krstić
authors.forename: Mira S
authors.initials: MS
authors.lastname: Bjelaković
authors.forename: Vladimir D
authors.initials: VD
authors.lastname: Pavlović
authors.forename: Koen
authors.initials: K
authors.lastname: Robeyns
authors.forename: Zorica D
authors.initials: ZD
authors.lastname: Juranić
authors.forename: Ivana
authors.initials: I
authors.lastname: Matić
authors.forename: Irena
authors.initials: I
authors.lastname: Novaković
authors.forename: Dušan M
authors.initials: DM
authors.lastname: Sladić
mesh_terms: D000736:Androstenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001156:Artemia / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000187:drug effects
chemical_list: D000736:Androstenes; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents