Novel thiosemicarbazide derivatives with 4-nitrophenyl group as multi-target drugs: α-glucosidase inhibitors with antibacterial and antiproliferative activity

Maciej Wos; Małgorzata Miazga-Karska; Agnieszka A Kaczor; Katarzyna Klimek; Zbigniew Karczmarzyk; Dorota Kowalczuk; Waldemar Wysocki; Grazyna Ginalska; Zofia Urbanczyk-Lipkowska; Maja Morawiak; Monika Pitucha

doi:10.1016/j.biopha.2017.07.049

Novel thiosemicarbazide derivatives with 4-nitrophenyl group as multi-target drugs: α-glucosidase inhibitors with antibacterial and antiproliferative activity

Biomed Pharmacother. 2017 Sep:93:1269-1276. doi: 10.1016/j.biopha.2017.07.049.

Affiliations

¹ Department of Organic Chemistry, Medical University, 4A Chodzki St., PL-20093, Lublin, Poland.
² Department of Biochemistry and Biotechnology, Medical University,1 Chodzki St., PL-20093, Lublin, Poland.
³ Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Medical University,1 Chodzki St., PL-20093, Lublin, Poland; University of Eastern Finland, School of Pharmacy, Department of Pharmaceutical Chemistry, Yliopistonranta 1, P.O. Box 1627, FI-70211, Kuopio, Finland.
⁴ Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54 St., PL-08110, Siedlce, Poland.
⁵ Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4 St., PL-20090, Lublin, Poland.
⁶ Institute of Organic Chemistry, Polish Academy of Sciences,Kasprzaka 44/52 St., PL-01224, Warsaw, Poland.
⁷ Department of Organic Chemistry, Medical University, 4A Chodzki St., PL-20093, Lublin, Poland. Electronic address: monika.pitucha@umlub.pl.

PMID: 28747001
DOI: 10.1016/j.biopha.2017.07.049

Abstract

A series of thiosemicarbazides with 4-nitrophenyl group was obtained in the reaction of carboxylic acid hydrazides with isothiocyanates. All compounds were checked for their antibacterial and antiproliferative activity. Our results have shown that derivatives 6-8 possessed antibacterial activity against S. aureus, S. epidermidis, S. mutans and S. sanguinis, moderate cytotoxicity and good therapeutic safety in vitro. Additionally, compounds 1 and 4 significantly inhibited A549, HepG2 and MCF-7 cell division. Moreover, PASS software indicated that newly obtained compounds are potential α-glucosidase inhibitors. This was confirmed by in vitro studies. To investigate the mode of interaction with the molecular target compounds were docked to glucose binding site of the enzyme and exhibited a similar binding mode as glucose.

Keywords: Antibacterial activity; Antiproliferative activity; Molecular docking; Thiosemicarbazide; α-glucosidase inhibitor.

MeSH terms

A549 Cells
Anti-Bacterial Agents / pharmacology*
Bacteria / drug effects
Binding Sites
Cell Line
Cell Proliferation / drug effects*
Glycoside Hydrolase Inhibitors / pharmacology*
Hep G2 Cells
Humans
MCF-7 Cells
Molecular Docking Simulation
Nitrophenols / pharmacology*
Semicarbazides / pharmacology*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Glycoside Hydrolase Inhibitors
Nitrophenols
Semicarbazides
4-nitrophenyl
thiosemicarbazide