Inhibitors of Glucosamine-6-phosphate Synthase As Potential Antimicrobials or Antidiabetics - Synthesis and Properties

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Jul 8

PMID 35801410

Authors

Joanna Stefaniak

Michal G Nowak

Marek Wojciechowski

Slawomir Milewski

Andrzej S Skwarecki

Affiliations

Soon will be listed here.

Abstract

Glucosamine-6-phosphate synthase (GlcN-6-P synthase) is known as a promising target for antimicrobial agents and antidiabetics. Several compounds of natural or synthetic origin have been identified as inhibitors of this enzyme. This set comprises highly selective l-glutamine, amino sugar phosphate or transition state intermediate -enolamine analogues. Relatively low antimicrobial activity of these inhibitors, poorly penetrating microbial cell membranes, has been improved using the pro-drug approach. On the other hand, a number of heterocyclic and polycyclic compounds demonstrating antimicrobial activity have been presented as putative inhibitors of the enzyme, based on the results of molecular docking to GlcN-6-P synthase matrix. The most active compounds of this group could be considered promising leads for development of novel antimicrobial drugs or antidiabetics, provided their selective toxicity is confirmed.

Citing Articles

In-vitro antibacterial and antibiofilm activities and in-silico analysis of a potent cyclic peptide from a novel Streptomyces sp. strain RG-5 against antibiotic-resistant and biofilm-forming pathogenic bacteria.

Driche E, Badji B, Mathieu F, Zitouni A Arch Microbiol. 2024; 206(11):450.

PMID: 39476249 DOI: 10.1007/s00203-024-04174-2.

Synthesis, pharmacological evaluation, and study of new 3-furan-1-thiophene-based chalcones as antibacterial and anticancer agents.

Abdula A, Mohsen G, Jasim B, Jabir M, Rushdi A, Baqi Y Heliyon. 2024; 10(11):e32257.

PMID: 38947436 PMC: 11214363. DOI: 10.1016/j.heliyon.2024.e32257.

Logic programming-based Minimal Cut Sets reveal consortium-level therapeutic targets for chronic wound infections.

Mahout M, Carlson R, Simon L, Peres S NPJ Syst Biol Appl. 2024; 10(1):34.

PMID: 38565568 PMC: 10987626. DOI: 10.1038/s41540-024-00360-6.

A Metabolome and Microbiome Analysis of Acute Myeloid Leukemia: Insights into the Carnosine-Histidine Metabolic Pathway.

Wu B, Xu Y, Tang M, Jiang Y, Zhang T, Huang L Toxics. 2024; 12(1).

PMID: 38250970 PMC: 10821349. DOI: 10.3390/toxics12010014.

Design, Synthesis, Antimicrobial Properties, and Molecular Docking of Novel Furan-Derived Chalcones and Their 3,5-Diaryl-∆-pyrazoline Derivatives.

Mahdi I, Abdula A, Jassim A, Baqi Y Antibiotics (Basel). 2024; 13(1).

PMID: 38247580 PMC: 10812776. DOI: 10.3390/antibiotics13010021.

References

Vijesh A, Isloor A, Prabhu V, Ahmad S, Malladi S . Synthesis, characterization and anti-microbial studies of some novel 2,4-disubstituted thiazoles. Eur J Med Chem. 2010; 45(11):5460-4. DOI: 10.1016/j.ejmech.2010.07.048. View

Skwarecki A, Milewski S, Schielmann M, Milewska M . Antimicrobial molecular nanocarrier-drug conjugates. Nanomedicine. 2016; 12(8):2215-2240. DOI: 10.1016/j.nano.2016.06.002. View

Sujith K, Rao J, Shetty P, Kalluraya B . Regioselective reaction: synthesis and pharmacological study of Mannich bases containing ibuprofen moiety. Eur J Med Chem. 2009; 44(9):3697-702. DOI: 10.1016/j.ejmech.2009.03.044. View

Shyma P, Kalluraya B, Peethambar S, Telkar S, Arulmoli T . Synthesis, characterization and molecular docking studies of some new 1,3,4-oxadiazolines bearing 6-methylpyridine moiety for antimicrobial property. Eur J Med Chem. 2013; 68:394-404. DOI: 10.1016/j.ejmech.2013.07.019. View

Neuss N, Molloy B, Shah R, DeLaHiguera N . The structure of anticapsin, a new biologically active metabolite of Streptomyces griseoplanus. Biochem J. 1970; 118(4):571-5. PMC: 1179253. DOI: 10.1042/bj1180571. View

Raczynska J, Olchowy J, Konariev P, Svergun D, Milewski S, Rypniewski W . The crystal and solution studies of glucosamine-6-phosphate synthase from Candida albicans. J Mol Biol. 2007; 372(3):672-88. DOI: 10.1016/j.jmb.2007.07.002. View

Li L, Shao M, Peng P, Yang C, Song S, Duan F . High expression of GFAT1 predicts unfavorable prognosis in patients with hepatocellular carcinoma. Oncotarget. 2017; 8(12):19205-19217. PMC: 5386678. DOI: 10.18632/oncotarget.15164. View

Ren S, Shao Y, Zhao X, Hong C, Wang F, Lu X . Integration of Metabolomics and Transcriptomics Reveals Major Metabolic Pathways and Potential Biomarker Involved in Prostate Cancer. Mol Cell Proteomics. 2015; 15(1):154-63. PMC: 4762514. DOI: 10.1074/mcp.M115.052381. View

Pawlak D, Stolarska M, Wojciechowski M, Andruszkiewicz R . Synthesis, anticandidal activity of N(3)-(4-methoxyfumaroyl)-(S)-2,3-diaminopropanoic amide derivatives--novel inhibitors of glucosamine-6-phosphate synthase. Eur J Med Chem. 2014; 90:577-82. DOI: 10.1016/j.ejmech.2014.12.007. View

10.

Shah R, Neuss N, Gorman M, Boeck L . Isolation, purification, and characterization of anticapsin. Jpn J Antibiot. 1970; 23(6):613-7. View

11.

Marco-Contelles J, Molina M, Anjum S . Naturally occurring cyclohexane epoxides: sources, biological activities, and synthesis. Chem Rev. 2004; 104(6):2857-99. DOI: 10.1021/cr980013j. View

12.

Mouilleron S, Badet-Denisot M, Badet B, Golinelli-Pimpaneau B . Dynamics of glucosamine-6-phosphate synthase catalysis. Arch Biochem Biophys. 2010; 505(1):1-12. DOI: 10.1016/j.abb.2010.08.008. View

13.

Molloy B, LIVELY D, GALE R, Gorman M, Boeck L . A new dipeptide antibiotic from Streptomyces collinus, Lindenbein. J Antibiot (Tokyo). 1972; 25(2):137-40. DOI: 10.7164/antibiotics.25.137. View

14.

Bearne S . Active site-directed inactivation of Escherichia coli glucosamine-6-phosphate synthase. Determination of the fructose 6-phosphate binding constant using a carbohydrate-based inactivator. J Biol Chem. 1996; 271(6):3052-7. View

15.

Milewski S, Chmara H, Andruszkiewicz R, Borowski E, Zaremba M, Borowski J . Antifungal peptides with novel specific inhibitors of glucosamine 6-phosphate synthase. Drugs Exp Clin Res. 1988; 14(7):461-5. View

16.

Srinivasan V, Sandhya N, Sampathkumar R, Farooq S, Mohan V, Balasubramanyam M . Glutamine fructose-6-phosphate amidotransferase (GFAT) gene expression and activity in patients with type 2 diabetes: inter-relationships with hyperglycaemia and oxidative stress. Clin Biochem. 2007; 40(13-14):952-7. DOI: 10.1016/j.clinbiochem.2007.05.002. View

17.

Jose G, Suresha Kumara T, Nagendrappa G, Sowmya H, Jasinski J, Millikan S . New polyfunctional imidazo[4,5-C]pyridine motifs: synthesis, crystal studies, docking studies and antimicrobial evaluation. Eur J Med Chem. 2014; 77:288-97. DOI: 10.1016/j.ejmech.2014.03.019. View

18.

Buse M . Hexosamines, insulin resistance, and the complications of diabetes: current status. Am J Physiol Endocrinol Metab. 2005; 290(1):E1-E8. PMC: 1343508. DOI: 10.1152/ajpendo.00329.2005. View

19.

Melagraki G, Afantitis A, Igglessi-Markopoulou O, Detsi A, Koufaki M, Kontogiorgis C . Synthesis and evaluation of the antioxidant and anti-inflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts. Eur J Med Chem. 2009; 44(7):3020-6. DOI: 10.1016/j.ejmech.2008.12.027. View

20.

Oliveira I, Allonso D, Fernandes T, Lucena D, Ventura G, Dias W . Enzymatic and structural properties of human glutamine:fructose-6-phosphate amidotransferase 2 (hGFAT2). J Biol Chem. 2020; 296:100180. PMC: 7948480. DOI: 10.1074/jbc.RA120.015189. View