title: Synthesis and biological evaluation of some 17-picolyl and 17-picolinylidene androst-5-ene derivatives.
abstract: Starting from dehydroepiandrosterone (1) 17-picolyl (2), 17-picolinylidene (7), 17-picolinylidene-16-one (10 and 11), and 17-picolyl-16-one (15) derivatives of androst-5-ene were synthesized in one, two, four and five steps respectively. By the Oppenauer oxidation or dehydration of 2, 7, 10, and 11 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the corresponding A and B ring modified derivatives 3, 5, 6, 8, 9, and 12-14 were obtained. The structure of 2 was unambiguously proved by the appropriate X-ray structural analysis. Compounds 3, 5, 9, 12-14 showed inhibitory activity against the enzyme aromatase. Antibacterial activity, toxicity to brine shrimp Artemia salina, antitumor activity against three tumor cell lines (human cervix carcinoma HeLa cells, human melanoma FemX cells, and human myelogenous leukemia K562 cells) and toxicity against peripheral blood mononuclear cells were evaluated. Three tested compounds, namely 11, 13, and 15, showed strong activity against all three cell lines, the IC(50) values being in the range of 4-10 microM.
authors.affiliation: Department of Chemistry, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 3, Serbia. kpg@ih.ns.ac.yu
authors.forename: Katarina M Penov
authors.initials: KM
authors.lastname: Gasi
authors.forename: Maja Dj Djurendić
authors.initials: MDj
authors.lastname: Brenesel
authors.forename: Evgenija A
authors.initials: EA
authors.lastname: Djurendić
authors.forename: Marija N
authors.initials: MN
authors.lastname: Sakac
authors.forename: Janos J
authors.initials: JJ
authors.lastname: Canadi
authors.forename: Jovana J
authors.initials: JJ
authors.lastname: Daljev
authors.forename: Thomas
authors.initials: T
authors.lastname: Armbruster
authors.forename: Silvana
authors.initials: S
authors.lastname: Andrić
authors.forename: Dusan M
authors.initials: DM
authors.lastname: Sladić
authors.forename: Tatjana T
authors.initials: TT
authors.lastname: Bozić
authors.forename: Irena T
authors.initials: IT
authors.lastname: Novaković
authors.forename: Zorica D
authors.initials: ZD
authors.lastname: Juranić
mesh_terms: D000736:Androstenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C518804:3-acetoxy-17-picolinylideneandrost-5-ene-16-one; C518805:3-acetoxy-17-picolinylmethylandrost-5-ene-16-one; C518803:3-hydroxy-17-picolinylideneandrost-5-ene-16-one; D000736:Androstenes; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D001141:Aromatase