Design of a Thiosemicarbazide-Functionalized Calix[4]arene Ligand and Related Transition Metal Complexes: Synthesis, Characterization, and Biological Studies

Ehsan Bahojb Noruzi; Mahsa Kheirkhahi; Behrouz Shaabani; Silvano Geremia; Neal Hickey; Fioretta Asaro; Patrizia Nitti; Hossein Samadi Kafil

doi:10.3389/fchem.2019.00663

Design of a Thiosemicarbazide-Functionalized Calix[4]arene Ligand and Related Transition Metal Complexes: Synthesis, Characterization, and Biological Studies

Front Chem. 2019 Oct 9:7:663. doi: 10.3389/fchem.2019.00663. eCollection 2019.

Authors

Ehsan Bahojb Noruzi¹, Mahsa Kheirkhahi¹, Behrouz Shaabani¹, Silvano Geremia², Neal Hickey², Fioretta Asaro², Patrizia Nitti², Hossein Samadi Kafil³

Affiliations

¹ Department of Inorganic Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.
² Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy.
³ Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

In this study, we synthesized a new thiosemicarbazide-functionalized calix[4]arene L and its Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺ transition metal complexes. For characterization several techniques were employed: Fourier-transform infrared (FT-IR), ¹H nuclear magnetic resonance (NMR), ¹³C-NMR, ¹⁵N-NMR, correlation spectroscopy (COZY), nuclear Overhauser enhancement spectroscopy (NOESY), electrospray ionization (ESI)-mass spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and elemental analysis. To explore the capability of the thiosemicarbazide function hosted on a calix[4]arene scaffold for growth inhibition of bacteria, fungi, and cancerous tumor cells, a series of biological evaluations were performed. For L, the antimicrobial tests revealed a higher antibacterial activity against gram-positive Bacillus subtilis and a lower activity against gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), whereas the gram-positive Staphylococcus aureus shows resistance. All examined metal derivatives show an enhancement of the antibacterial activity against gram-negative E. coli bacteria, with a more significant improvement for the Ni²⁺ and Zn²⁺ complexes. MTT assays showed a considerable in vitro anticancer activity of Co²⁺, Ni²⁺, and Cu²⁺ complexes against Saos-2 bone cancer cell lines. The activity is ascribable to the inorganic ions rather than calixarene ligand. Hemolysis assay results demonstrated that all compounds have high blood compatibility.

Keywords: anticancer; antimicrobial; calix[4]arene; ligand; thiosemicarbazide; transition metal complex.