title: Antitumor activity of newly synthesized oxo and ethylidene derivatives of bile acids and their amides and oxazolines.
abstract: Bile acid derivatives with modifications in side chain and modifications on steroid skeleton were synthetized and their antitumor activity against five human cancer cell lines was investigated. Modifications in side chain include amid group, formed in reaction with 2-amino-2-methylpropanol, and 4,4-dimethyloxazoline group, obtained after cyclization of amides. In the steroid skeleton oxo groups were introduced in position 7 (2, 2a, 2b) and 7,12 (3, 3a, 3b). Ethylidene groups were introduced regio- and stereoselectively on C-7, and/or without stereoselectivity on C-3 by Wittig reaction. By combination of these modifications, a series of 19 bile acid derivatives were synthesized. Compounds containing both C-7 ethylidene and C-12 carbonyl groups (6, 6a, 6b) shown very good antitumor activity with IC50<5µM. Altering carboxylic group to amide or oxazoline group has positive effect on cytotoxicity. Different molecular descriptors were determined in silico and after principal component analysis was found that molecular descriptor BLTF96 can be used for fast assessment of experimental cytotoxicity of bile acid derivatives.
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: srdjan.bjedov@dh.uns.ac.rs.
authors.forename: Srđan
authors.initials: S
authors.lastname: Bjedov
authors.affiliation: Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Institutski put 4, 21204 Sremska Kamenica, Serbia.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Jakimov
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljka 3, 21000 Novi Sad, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Pilipović
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljka 3, 21000 Novi Sad, Serbia.
authors.forename: Mihalj
authors.initials: M
authors.lastname: Poša
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovića 3, 21000 Novi Sad, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Sakač
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry; D011412:Propanolamines / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D001647:Bile Acids and Salts; D010080:Oxazoles; D011412:Propanolamines; C057549:4,4-dimethyloxazoline; C006551:2-amino-2-methyl-1-propanol
keywords: Amide; Antitumor activity; Bile acid; Ethylidene; Oxazoline; Wittig reaction