title: Preselection of A- and B- modified d-homo lactone and d-seco androstane derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.
abstract: The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d-homo lactone and d-seco androstane derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d-homo lactone and/or d-seco androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- (3) and 6α,7α-epoxy-1,4-dien-3-one (24) d-homo lactone androstane derivatives, as well as 4-en-3-one (15) d-seco androstane derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer - abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d-homo lactone and d-seco androstane derivatives with antiproliferative activity against breast and prostate cancer cells.
authors: University of Novi Sad, Faculty of Technology Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia. Electronic address: strahko@uns.ac.rs.
authors: Strahinja Z
authors: SZ
authors: Kovačević
authors: University of Novi Sad, Faculty of Technology Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia.
authors: Sanja O
authors: SO
authors: Podunavac-Kuzmanović
authors: University of Novi Sad, Faculty of Technology Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia.
authors: Lidija R
authors: LR
authors: Jevrić
authors: University of Novi Sad, Faculty of Technology Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia.
authors: Vladimir R
authors: VR
authors: Vukić
authors: University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
authors: Marina P
authors: MP
authors: Savić
authors: University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
authors: Evgenija A
authors: EA
authors: Djurendić
mesh_terms: D000731:Androstanes / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D062105:Molecular Docking Simulation; D011471:Prostatic Neoplasms / Q000473:pathology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000731:Androstanes; D007783:Lactones
keywords: Antiproliferative activity; Artificial neural networks; Chemometrics; Molecular docking; QSAR; d-homo lactone and d-seco androstane derivatives