Synthesis, characterization, antimicrobial and cytotoxic effects of Mn(II), Cu(II), Zn(II) and Bi(III) complexes with hydrazone derivatives of girard’s reagent P and T

Abstract

U ovom radu opisana je sinteza, karakterizacija i kristalna struktura kompleksa 1, nastalog između jona Zn(II) i (E)-1-(2-okso-2-(2-(hinolin-2-ilmetilen)hidrazinil)etil)piridin- -ijum-hlorida (HL1Cl) i kompleksa 2, 3, 4 i 5, nastalih između jona Cu(II), Mn(II), Zn(II) i Bi(III) sa (E)-N,N,N-trimetil-2-okso-2-(2-(1-(tiazol-2-il)etiliden)hidrazinil)etan-1-aminijum hloridom (HL2Cl). Svi kompleksi okarakterisani su rendgenskom strukturnom analizom, elementalnom analizom i IC spektroskopijom. U slučaju kompleksa 1 ligand HL1Cl koordinovan je u deprotonovanom obliku preko hinolinskog atoma azota, azometinskog atoma azota i karbonilnog atoma kiseonika. Ligand HL2Cl u kompleksima 2–4 koordinovan je u deprotonovanom formalno neutralnom cviterjonskom obliku preko NNO donorskog seta atoma, dok u kompleksu 5 ostaje u protonovanoj formi. Ispitana je antimikrobna aktivnost, test na račićima Artemia salina i DPPH test na svim kompleksima. Antimikrobna aktivnost je ispitana na pet sojeva Gram-pozitivnih i pet sojeva Gram-negativnih bakterija, dva soja kvasaca i jednom soju gljivica. Određena je i citotoksična aktivnost prema pet malignih ćelijskih linija (HeLa, A375, MCF7, PC-3 i A549) i jednoj normalnoj ćelijskoj liniji (HaCaT). Nije ispitivana citotoksična aktivnost kompleksa 5 usled njegove hidrolize u rastvoru DMSO. Kompleks 1 pokazao je značajnu antibakterijsku aktivnost posebno prema Gram-negativnim bakterijama, sa aktivnošću sličnoj hloramfenikolu, dok je dinuklearni kompleks 3 pokazao antifungalnu aktivnost sličnog intenziteta sa amfotericinom B. Kompleksi 2 i 3 pokazali su značajnu citotoksičnu aktivnost, pri čemu je aktivnost kompleksa 3 tek neznatno slabija od one koju pokazuje cisplatin prema ćelijama MCF7.In this work synthesis, characterization and crystal structures of 1, Zn(II) complex ([ZnL1(NCS)2]), with (E)-1-(2-oxo-2-(2-(quinolin-2-ylmethylene)hydrazinyl)ethyl)pyridin- -1-ium chloride (HL1Cl) and 2, 3, 4 and 5, Cu(II), Mn(II), Zn(II) and Bi(III) complexes with (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL2Cl) are represented. All complexes are characterized by X-ray crystallographic analysis, elemental analysis and IR spectroscopy. In case of complex 1 hydrazone ligand HL1Cl is coordinated in deprotonated form through the quinoline nitrogen, azomethine nitrogen and carbonyl oxygen atoms. Hydrazone ligand HL2Cl in complexes 2–4 is coordinated in deprotonated formally neutral zwitter-ionic form via NNO donor set atoms, while in complex 5 it remains in protonated form. Antimicrobial activity, brine shrimp assay and DPPH radical scavenging activity of all complexes was evaluated. Antimicrobial activity was tested against a five Gram-negative and five Gram-positive bacteria, two yeasts and one fungal strain. Cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and normal cell line HaCaT was tested as well. Due to hydrolysis that is occurring in DMSO solution of complex 5, this complex was not tested for cytotoxic activity. Complex 1 showed a significant antibacterial activity especially towards Gram-negative bacteria, with intensity similar to chloramphenicol, while the binuclear Mn(II) complex (3) showed antifungal activity of similar intensity as amphotericin B. Complexes 2 and 3 showed a significant cytotoxic activity. The activity of Mn(II) complex (3) is only slightly weaker than that of cisplatin against breast cancer MCF7 cells