title: Synthesis, cytotoxic effect, and structure-activity relationship of Pd(II) complexes with coumarin derivatives.
abstract: We report the influence of the substituent at the N atom of the ligands on the synthesis, biological activity, and stability of Pd(II) complexes of the general formula PdL(2). The compounds adopt a cis or trans configuration with respect to the substituent at the nitrogen atom. Sterically hindered substituents promote the formation of trans isomers, whereas when the nitrogen atom is unsubstituted, cis isomers are formed. The compounds were characterized by elemental analysis, infrared and 1H NMR spectroscopies, and electrospray mass spectrometry. The complexes were also studied using X-ray diffraction and computational DFT methods. Both complexes cis-3a and trans-3c exhibit square-planar geometries around the Pd(II) atom. The cytotoxic effects of these complexes were examined on two human leukemia cell lines, HL-60 and NALM-6. Pd complex cis-3a showed significant cytotoxic activity. The effects exhibited by this complex were comparable to those reported for carboplatin. Loigand 2a was not cytotoxic. Computational analysis carried out at the PB/B3LYP/LACVP**//mPW1PW91/LanL2DZ level showed excellent correlation between the energy difference of the cis and trans isomers and the cytotoxic activity, rendering computations a useful predictive tool for the design of new drugs.
authors.affiliation: Department of Cosmetic Raw Materials Chemistry, Faculty of Pharmacy, Medical University of Łódź, Łódź, Poland. elora@ich.pharm.am.lodz.pl
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Budzisz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Małecka
authors.forename: Ingo-Peter
authors.initials: IP
authors.lastname: Lorenz
authors.forename: Peter
authors.initials: P
authors.lastname: Mayer
authors.forename: Renata A
authors.initials: RA
authors.lastname: Kwiecień
authors.forename: Piotr
authors.initials: P
authors.lastname: Paneth
authors.forename: Urszula
authors.initials: U
authors.lastname: Krajewska
authors.forename: Marek
authors.initials: M
authors.lastname: Rózalski
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D003374:Coumarins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D009944:Organoplatinum Compounds; C030123:coumarin; D009584:Nitrogen