Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 9;15(8):979.
doi: 10.3390/ph15080979.

Chelation of Zinc with Biogenic Amino Acids: Description of Properties Using Balaban Index, Assessment of Biological Activity on Spirostomum Ambiguum Cellular Biosensor, Influence on Biofilms and Direct Antibacterial Action

Alla V Marukhlenko  1 , Mariya A Morozova  1 , Arsène M J Mbarga  2 , Nadezhda V Antipova  3 , Anton V Syroeshkin  1 , Irina V Podoprigora  2 , Tatiana V Maksimova  1
Affiliations

Chelation of Zinc with Biogenic Amino Acids: Description of Properties Using Balaban Index, Assessment of Biological Activity on Spirostomum Ambiguum Cellular Biosensor, Influence on Biofilms and Direct Antibacterial Action

Alla V Marukhlenko et al. Pharmaceuticals (Basel). .

Abstract

The complexation of biogenic molecules with metals is the widespread strategy in screening for new pharmaceuticals with improved therapeutic and physicochemical properties. This paper demonstrates the possibility of using simple QSAR modeling based on topological descriptors for chelates study. The presence of a relationship between the structure (J) and lipophilic properties (logP) of zinc complexes with amino acids, where two molecules coordinate the central atom through carboxyl oxygen and amino group nitrogen, and thus form a double ring structure, was predicted. Using a cellular biosensor model for Gly, Ala, Met, Val, Phe and their complexes Zn(AA)2, we experimentally confirmed the existence of a direct relationship between logP and biological activity (Ea). The results obtained using topological analysis, Spirotox method and microbiological testing allowed us to assume and prove that the chelate complex of zinc with methionine has the highest activity of inhibiting bacterial biofilms, while in aqueous solutions it does not reveal direct antibacterial effect.

Keywords: Balaban index; QSAR; antibacterial properties; biosensor Spirostomum ambiguum; coordination biochemistry; laser light scattering; methionine; zinc.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of glycine (a) and its zinc chelate compound—zinc glycinate (b).
Figure 2
Figure 2
Dependence of lipophilicity on Balaban index for amino acids and their chelate compounds with Zn.
Figure 3
Figure 3
Dependence of biological activity (obsEa) and lipophilicity on Balaban index for amino acids (a) and for their chelate compounds with Zn (b).
Figure 4
Figure 4
Comparison of the tested Zn(AA)2 complexes according to their inhibition influence on E. coli biofilm formation (n = 3), black—Zn(Ala)2, blue—Zn(Met)2, green—Zn(Val)2, grey—Zn(Gly)2, orange—Zn(Phe)2. Insert shows mean numerical particle size distribution for control (red) and test solutions of zinc amino acid complexes with SD (n = 3).
Figure 5
Figure 5
Comparison of the mean total particle surface area of the control and the test solution of zinc methioninate depending on the particle size (n = 3), red—control, blue—Zn(Met)2 solution.
Figure 6
Figure 6
Scheme of cell transitions of bacterial culture in the presence of zinc chelate complex, C—single cell, Cn—cellular associates of bacterial culture, C#—dead cells.
Figure 7
Figure 7
Antibiofilm activity of zinc methioninate complex, Staphylococus aureus 1449—circle black, Staphylococcus aureus ATCC 6538—unfilled square black, Staphylococcus simulans 5882—unfilled circle black, Escherichia coli M17—circle blue, Escherichia coli ATCC 25922—unfilled square blue, Streptococcus agalactiae 3984—circle red, Enterococcus cloacae 6392—circle green, Acinetobacter baumannii 5841—circle pink.
Figure 8
Figure 8
Scheme of antibiofilm activity determination on the example of Staphylococcus aureus 1449, Escherichia coli M17 and Streptococcus agalactiae 3984 bacterial strains: 96-well microtiter plate with 99% ethanol after the solubilization of biofilm-bound crystal violet.
See this image and copyright information in PMC

References

    1. Moriwa Y., Suzuki N., Shoji A., Yanagida A. Analysis of complexation interactions between metal ions and drugs under pseudo-physiological pH conditions by a high-throughput screening method using a solid-phase extraction cartridge. Anal. Sci. 2020;36:709–715. doi: 10.2116/analsci.19P413. - DOI - PubMed
    1. Nagy L., Csintalan G., Kálmán E., Sipos P., Szvetnik A. Fémionok és fémkomplexek alkalmazása az orvostudományban I [Applications of metal ions and their complexes in medicine I] Acta Pharm. Hung. 2003;73:221–236. - PubMed
    1. Jurca T., Marian E., Vicaş L.G., Mureşan M., Fritea L. Metal Complexes of Pharmaceutical Substances. In: Sharmin E., Zafar F., editors. Spectroscopic Analyses—Developments and Applications. IntechOpen; London, UK: 2017. - DOI
    1. Sarkar K., Sen K. Some drugs in action: Metal ions do influence the activity! IJPSR. 2015;6:1–13.
    1. Pattan S.R., Pawar S.B., Vetal S.S., Gharate U.D., Bhawar S.B. The scope of metal complexes in drug design—A review. Indian Drugs. 2012;49:5–12. doi: 10.53879/id.49.11.p0005. - DOI

LinkOut - more resources