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Open AccessArticle

Synthesis, Crystal Structure, and Biological Activity of a Multidentate Calix[4]arene Ligand Doubly Functionalized by 2-Hydroxybenzeledene-Thiosemicarbazone

Department of Inorganic Chemistry, Faculty of Chemistry, University of Tabriz, 5166616471 Tabriz, Iran
Centre of Excellence in Biocrystallography, Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy
Drug Applied Research Center, Tabriz University of Medical Sciences, 5154853431 Tabriz, Iran
Authors to whom correspondence should be addressed.
Academic Editors: Mario Berberan-Santos and Paula M. Marcos
Molecules 2020, 25(2), 370;
Received: 11 November 2019 / Revised: 10 January 2020 / Accepted: 14 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Calixarene Complexes: Synthesis, Properties and Applications)
The design and synthesis of a novel tert-butyl-calix[4]arene functionalized at 1, 3 positions of the lower rim with two terminal 2-hydroxybenzeledene-thiosemicarbazone moieties is reported. The new ligand with multi-dentate chelating properties was fully characterized by several techniques: ESI-Mass spectroscopy, FT-IR, 1H-NMR, and single crystal X-ray diffraction. The solid state structure confirms that the calix[4]arene macrocycle has the expected open cone conformation, with two opposite phenyl rings inclined outwards with large angles. The conformation of the two alkoxythiosemicarbazone arms produces a molecule with a C2 point group symmetry. An interesting chiral helicity is observed, with the two thiosemicarbazone groups oriented in opposite directions like a two-blade propeller. A water molecule is encapsulated in the center of the two-blade propeller through multiple H-bond coordinations. The antibacterial, antifungal, anticancer, and cytotoxic activities of the calix[4]arene-thiosemicarbazone ligand and its metal derivatives (Co2+, Ni2+, Cu2+, and Zn2+) were investigated. A considerable antibacterial activity (in particular against E. coli, MIC, and MBC = 31.25 μg/mL) was observed for the ligand and its metal derivatives. Significant antifungal activities against yeast (C. albicans) were also observed for the ligand (MIC = 31.25 μg/mL and MBC = 125 μg/mL) and for its Co2+ derivative (MIC = 62.5 μg/mL). All compounds show cytotoxicity against the tested cancerous cells. For the Saos-2 cell line, the promising anticancer activity of ligand L (IC50 < 25 μg/mL) is higher than its metal derivatives. The microscopic analysis of DAPI-stained cells shows that the treated cells change in morphology, with deformation and fragmentation of the nuclei. The hemo-compatibility study demonstrated that this class of compounds are suitable candidates for further in vivo investigations. View Full-Text
Keywords: thiosemicarbazone; calix[4]arene; metal complex; X-ray structure; antimicrobial; anticancer thiosemicarbazone; calix[4]arene; metal complex; X-ray structure; antimicrobial; anticancer
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MDPI and ACS Style

Bahojb Noruzi, E.; Shaabani, B.; Geremia, S.; Hickey, N.; Nitti, P.; Kafil, H.S. Synthesis, Crystal Structure, and Biological Activity of a Multidentate Calix[4]arene Ligand Doubly Functionalized by 2-Hydroxybenzeledene-Thiosemicarbazone. Molecules 2020, 25, 370.

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