Synthesis, structural, cytotoxic and pharmacokinetic evaluation of some thiosemicarbazone derivatives

Abstract

Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one‐pot synthesis method. The structures were characterized by elemental analysis, IR, 1H NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single‐crystal X‐ray diffraction. The findings showed that the metal atom adopts a slightly distorted square‐pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular O─H···O and C─H···O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake‐flask method, another pharmacokinetic parameter. The findings showed that the IC50 values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies.

Iron(III) complexes based on tetradentate thiosemicarbazones: Synthesis, characterization, radical scavenging activity andin vitrocytotoxicity on K562, P3HR1 and JURKAT cells

“…[67] Two of them metabolized by cytochrome P450 (CYP) enzymes are cytotoxic in IC 50 values of 1.34-5.13 μM range against Caco2, HCT116, Hep3B, HepG2 cancerous cell lines from different origins. [68] Another analogous complex has been reported to exhibit usable cytotoxicity on HT-29 and HeLa cells in the 11-16 μM range of IC 50 by binding to DNA with 10 5 of intrinsic constant. [61] When the structure-activity relationship is evaluated, it was seen that the cytotoxic performances of Fe2, Fe5, and Fe8 having 4-OCH 3 group were superior to the others.…”

Thiosemicarbazone Derivatives Act as Potent Urease Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study

“…The biological versatility of thiosemicarbazones as antimalarial, antibacterial, anticancer, antifungal, antitumor, and urease inhibitor made them multifaceted and potent agents. [10][11][12][13][14][15][16][17][18] It was also observed that different series of molecular structures showing close homology with urea/thiourea moiety, such as the (thio)semicarbazones, [19,20] N-phenyl thiosemicarbazones, [21] hydrazones [22] led to urease inhibitory activity. [23] The structure of some of the reported thiosemicarbazone derivatives as urease inhibitors is presented in Figure 1b.…”

“…Thiosemicarbazone family are interesting molecules from a medicinal chemistry viewpoint because of their broad range of biological activities. The biological versatility of thiosemicarbazones as antimalarial, antibacterial, anticancer, antifungal, antitumor, and urease inhibitor made them multifaceted and potent agents [10–18] . It was also observed that different series of molecular structures showing close homology with urea/thiourea moiety, such as the (thio)semicarbazones, [19,20] N‐phenyl thiosemicarbazones, [21] hydrazones [22] led to urease inhibitory activity [23] .…”