title: Theoretical investigations and density functional theory based quantitative structure-activity relationships model for novel cytotoxic platinum(IV) complexes.
abstract: Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure-activity relationships must be drawn. Herein, we report on theoretical and QSAR investigations of a series of 53 novel bis-, tris-, and tetrakis(carboxylato)platinum(IV) complexes, synthesized and tested for cytotoxicity in our laboratories. The hybrid DFT functional wb97x was used for optimization of the structure geometry and calculation of the descriptors. Reliable and robust QSAR models with good explanatory and predictive properties were obtained for both the cisplatin sensitive cell line CH1 and the intrinsically cisplatin resistant cell line SW480, with a set of four descriptors.
authors.affiliation: Institute of Inorganic Chemistry,  University of Vienna , Währinger Strasse 42, A-1090 Vienna, Austria.
authors.forename: Hristo P
authors.initials: HP
authors.lastname: Varbanov
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Alexander
authors.initials: A
authors.lastname: Roller
authors.forename: Frank
authors.initials: F
authors.lastname: Jensen
authors.forename: Mathea Sophia
authors.initials: MS
authors.lastname: Galanski
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D016190:Carboplatin / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005021:Ethylamines / Q000737:chemistry / Q000494:pharmacology; D005029:Ethylenediamines / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology; D000077150:Oxaliplatin; D010984:Platinum; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005021:Ethylamines; D005029:Ethylenediamines; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; C053989:nedaplatin; D016190:Carboplatin; D002945:Cisplatin