Structure-activity relationship and cytotoxicity of the new thiosemicarbazide derivatives and their Cu(II) complexes against prostate and melanoma cancer cells.

Autor: Rogalewicz B; Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland. Electronic address: bartlomiej.rogalewicz@dokt.p.lodz.pl., Pitucha M; Independent Radiopharmacy Unit, Faculty of Pharmacy, Medical University of Lublin, Chodzki 4a, 20-093, Lublin, Poland., Świątkowski M; Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland., Humeniuk E; Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b, 20-093, Lublin, Poland., Adamczuk G; Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b, 20-093, Lublin, Poland., Drózd M; Independent Radiopharmacy Unit, Faculty of Pharmacy, Medical University of Lublin, Chodzki 4a, 20-093, Lublin, Poland., Karczmarzyk Z; Department of Chemistry, University of Siedlce, 3 Maja 54, 08-110, Siedlce, Poland., Kuśmierek E; Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland., Strzelec K; Institute of Polymer & Dye Technology, Faculty of Chemistry, Lodz University of Technology, Stefanowskiego 12/16, 90-924, Lodz, Poland., Raducka A; Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland., Wysocki W; Department of Chemistry, University of Siedlce, 3 Maja 54, 08-110, Siedlce, Poland., Olender A; Chair and Department of Medical Microbiology, Medical University of Lublin, Chodzki 1, 20-093, Lublin, Poland., Kozub A; Department of Bioanalytics, Faculty of Biomedicine, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland., Kowalczuk D; Chair and Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland., Poleszak E; Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Chodzki 1, 20-093, Lublin, Poland., Czylkowska A; Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland. Electronic address: agnieszka.czylkowska@p.lodz.pl.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 May; Vol. 755, pp. 109955. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1016/j.abb.2024.109955
Abstrakt: In this study, eighteen new ligands (B1-B18) containing a thiosemicarbazide core were synthesized and characterized in terms of physicochemical properties, molecular docking and in vitro biological activity. The structures of eleven ligands were investigated using X-Ray diffraction and Hirschfeld Surface analysis. To study the structure-activity relationship, the organic ligands contained pyridin-2-ylmethyl, pyridin-3-ylmethyl or pyridin-4-ylmethyl moieties and various substituents. Their pharmakokinetic profiles and molecular docking results suggest high potential as new drug candidates. The complexing ability of the selected organic ligands was also evaluated, yielding five new Cu(II) complexes (Cu(B1)Cl 2 , Cu(B4)Cl 2 , Cu(B10)Cl 2 , Cu(B17)Cl 2 , Cu(B18)Cl 2 ). The obtained results suggest the formation of the polymeric structures. All organic ligands and Cu(II) complexes were tested for anticancer activity against prostate and melanoma cancer cells (PC-3, DU-145, LNCaP, A375, G-361, SK-MEL-28) and normal fibroblasts (BJ), as well as antimicrobial activity against six selected bateria strains. Among B1-B18 compounds, B3, B5, B9, B10, B12 and B14 exhibited cytotoxic activity. The studied Cu(II) complexes were in general more active, with Cu(B1)Cl 2 exhibiting antincancer activity agains all three prostate cancer cells and Cu(B10)Cl 2 reaching the IC 50 value equal to 88 μM against G-361 melanoma cells. Several compounds also exhibited antimicrobial activity against gram-positive and gram-negative bacteria. It was found that the type of specific substituents, especially the presence of -chloro and -dichloro substituents had a greated impact on the cytotoxicity than the position of the nitrogen atom in the pyridylacetyl moiety.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: