Molecular Insight of the Possible Inhibition Mechanism of Therapeutic Cephalosporin Derivatives against Human Glutathione Reductase Enzyme

Muhammet Karaman

doi:10.17776/csj.678045

EN

Molecular Insight of the Possible Inhibition Mechanism of Therapeutic Cephalosporin Derivatives against Human Glutathione Reductase Enzyme

Abstract

Glutathione reductase is a key enzyme for glutathione metabolism. Inhibition of the enzyme activity related to various health problems. Therefore, determination of inhibitors of the enzyme and its possible inhibition mechanism are quite important. Some cephalosporins have exhibited potent inhibitory effect against human glutathione reductase (hGR). In order to understand the inhibition mechanism of the cephalosporins, we carried out molecular docking studies with Glide docking and Induced-fit Docking methods. Binding sites of hGR were predicted and the best suitable binding site of the drugs was identified with the Glide docking method. The binding affinity of the drugs was calculated with the induced-fit docking method. The best binding site of the drugs was detected as a part of the catalytic active site for Cefoperazone, Cefodizime, and Ceftazidime, dimerization site for Cefotaxime, Ceftriaxone, and Cefuroxime, and aromate binding site for Ceftizoxime. The Binding affinity of the Cefoperazone was calculated as -10.643 kcal/mol. The results have indicated that hGR enzyme would be inhibited with different mechanisms because of its several druggable sites. These findings would be helpful for designing new inhibitors for hGR enzyme and understanding of potential inhibition mechanism of its other known inhibitors.

Keywords

References

[1] Johnson A.E., Antibiotics, Am. J. Nurs., 50(11) (1950) 688-690.
[2] McManus M.C., Mechanisms of bacterial resistance to antimicrobial agents, Am J Health Syst Pharm, 54(12) (1997) 1420-1433; quiz 1444-1426.
[3] Hancock R.E., Peptide antibiotics, Lancet, 349(9049) (1997) 418-422.
[4] Poehlsgaard J., Douthwaite S., The bacterial ribosome as a target for antibiotics, Nature Reviews Microbiology, 3(11) (2005) 870-881.
[5] Spratt B.G., Resistance to antibiotics mediated by target alterations, Science, 264(5157) (1994) 388-393.
[6] Maxwell A., DNA gyrase as a drug target, Trends in Microbiology, 5(3) (1997) 102-109.
[7] Ahmad S.I., Kirk S.H., Eisenstark A., Thymine metabolism and thymineless death in prokaryotes and eukaryotes, Annual Review of Microbiology, 52 (1998) 591-625.
[8] Berdy J., Recent developments of antibiotic research and classification of antibiotics according to chemical structure, Adv Appl Microbiol, 18(0) (1974) 309-406.

[9] Maddison J.E., Watson A.D.J., Elliott J., Antibacterial drugs. In small animal climical pharmacology, 2nd ed. Philadelphia: Elsevier, 2008; 145-185.
[10] Farrington M., Antibacterial drugs. Clinical Pharmacology, 11th ed. London: Elsevier, 2012; 173-190.
[11] Watkins R. R., Bonomo R. A., β- Lactam antibiotics Anti-infective therapy, 4th ed. Amsterdam: Elsevier, 2017;1203-1216.e2.
[12] Moellering R.C., Swartz M.N., Drug therapy: the newer cephalosporins, N. Engl. J. Med., 294 (1976) 24-28.
[13] Mehta D., Sharma A.K., Cephalosporins: A review on imperative class of antibiotics, Molecular Pharmacology, 2016 (1) (2015) 1-6.
[14] Hughes D. L., Patent review of manufacturing routes to fifth-generation cephalosporin drugs. Part 1, Ceftolozane. Organic Process Research & Development, 21(3) (2017) 430-443.
[15] Deleve L.D., Kaplowitz N., Importance and regulation of hepatic glutathione, Seminars in Liver Disease, 10(4) (1990) 251-266.
[16] Anderson M.E., Glutathione: an overview of biosynthesis and modulation, Chemico-Biological Interactions, 112 (1998) 1-14.
[17] Karaman M., Akkemik E., Budak H. and Ciftci M., In vitro effects of some drugs on human erythrocyte glutathione reductase, Journal of Enzyme Inhibition and Medicinal Chemistry, 27(1) (2012) 18-23.
[18] Meister A., Anderson M.E., Glutathione, Annu Rev Biochem, 52 (1983) 711-760.
[19] Lii C.K., Chai Y.C., Zhao W., Thomas J.A. and Hendrich S., S-Thiolation and irreversible oxidation of sulfhydryls on carbonic-anhydrase-iii during oxidative stress - a method for studying protein modification in intact-cells and tissues, Archives of Biochemistry and Biophysics, 308(1) (1994) 231-239.
[20] Schirmer R.H., Krauth-Siegel R.L., Schulz G.E., Coenzymes and cofactors, New York: Vol. 3: John Wiley and Sons, 1989; 553-559.
[21] Senturk M., Kufrevioglu O.I. , Ciftci M., Effects of some antibiotics on human erythrocyte glutathione reductase: an in vitro study, Journal of Enzyme Inhibition and Medicinal Chemistry, 23(1) (2008) 144-148.
[22] Erat M., Sakiroglu H., Ciftci M., Effects of some antibiotics on glutathione reductase activities from human erythrocytes in vitro and from rat erythrocytes in vivo, Journal of Enzyme Inhibition and Medicinal Chemistry, 20 (1) (2005) 69-74.
[23] Dershwitz M., Novak R.F., Lack of inhibition of glutathione-reductase by un-nitrated derivatives of nitrofurantoin, Biochemical and Biophysical Research Communications, 92(4) (1980) 1313-1319.
[24] Ekinci D., Cankaya M., Gul I. and Coban T.A., Susceptibility of cord blood antioxidant enzymes glutathione reductase, glutathione peroxidase and glutathione S-transferase to different antibiotics: in vitro approach, J Enzyme Inhib Med Chem., 28(4) (2013) 824-829.
[25] Protein Preparation Wizard; Epik, Schrödinger, LLC, New York, NY, 2016; Impact, Schrödinger, LLC, New York, NY, 2016; Prime, Schrödinger, LLC, New York, NY, 2019.
[26] Kalin R., Koksal Z., Kalin P., Karaman M., Gulcin I. and Ozdemir, H. In vitro effects of standard antioxidants on lactoperoxidase enzyme-A molecular docking approach, J Biochem. Mol. Toxicol. (2019) e22421.
[27] Bayrak, C., Taslimi, P., Karaman, H. S., Gulcin, I. and Menzek A., The first synthesis, carbonic anhydrase inhibition and anticholinergic activities of some bromophenol derivatives with S including natural products, Bioorg Chem., 85 (2019) 128-139.
[28] SiteMap, Schrödinger, LLC, New York: NY. (2019).
[29] Bal S., Kaya R., Gok Y., Taslimi P., Aktas A., Karaman M. and Gulcin I., Novel 2-methylimidazolium salts: Synthesis, characterization, molecular docking, and carbonic anhydrase and acetylcholinesterase inhibitory properties, Bioorg Chem. (2019) 103468.
[30] LigPrep, Schrödinger, LLC, New York: NY. (2019).
[31] Taslimi P., Turkan F., Cetin A., Burhan H., Karaman M., Bildirici I., Gulcin I. and Sen F., Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials, Bioorg Chem, 92 (2019) 103213.
[32] Glide, Schrödinger, LLC, New York, NY (2019).
[33] Yigit B., Kaya R., Taslimi P., Isik Y., Karaman M., Yigit M., Ozdemir I. and Gulcin I. Imidazolinium chloride salts bearing wingtip groups: Synthesis, molecular docking and metabolic enzymes inhibition, J Mol Struct, 1179 (2019) 709-718.
[34] Turkan F., Cetin A., Taslimi P., Karaman H. S. and Gulcin I., Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives, Arch Pharm (Weinheim), 352(6) (2019) e1800359.
[35] Induced Fit Docking protocol; Glide, Schrödinger, LLC, New York, NY, 2016; Prime, Schrödinger, LLC, New York, NY. (2019).
[36] Bayindir S., Caglayan C., Karaman M. and Gulcin I., The green synthesis and molecular docking of novel N-substituted rhodanines as effective inhibitors for carbonic anhydrase and acetylcholinesterase enzymes, Bioorg Chem, 90 (2019) 103096.
[37] Erat M., Ciftci M., Effect of melatonin on enzyme activities of glutathione reductase from human erythrocytes in vitro and from rat erythrocytes in vivo, Eur J Pharmacol, 537(1-3) (2006) 59-63.
[38] Senturk M., Gulcin I., Ciftci M. and Kufrevioglu O.I., Dantrolene inhibits human erythrocyte glutathione reductase, Biological & Pharmaceutical Bulletin, 31(11) (2008) 2036-2039.
[39] Senturk M., Kufrevioglu O.I. and Ciftci M., Effects of some analgesic anaesthetic drugs on human erythrocyte glutathione reductase: an in vitro study, J Enzyme Inhib Med Chem, 24(2) (2009) 420-424.
[40] Akkemik E., Senturk M., Ozgeris F.B., Taser P., Ciftci M., In vitro eff ects of some drugs on human erythrocyte glutathione reductase, Turk J Med Sci, 42(2) (2011) 235-241.
[41] Friesner R.A., Banks J.L., Murphy R.B., Halgren T.A., Klicic J.J., Mainz D.T., Repasky M.P., Knoll E.H., Shelley M., Perry J.K., Shaw D.E., Francis P. and Shenkin P.S., Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy, J Med Chem, 47(7) (2004) 1739-1749.
[42] Sherman W., Beard H.S. and Farid R., Use of an induced fit receptor structure in virtual screening, Chem Biol Drug Des, 67(1) (2006) 83-84.
[43] Berkholz D.S., Faber H.R., Savvides S.N. and Karplus P.A., Catalytic cycle of human glutathione reductase near 1 A resolution, J Mol Biol, 382(2) (2008) 371-384.
[44] Sustmann R., Sicking W., Schulz G.E., The Active Site of Glutathione Reductase: An Example of Near Transition‐State Structures. Angew., Chem. Int. Ed. Eng., 28 (1989) 1023-1025.
[45] Nordhoff A., Tziatzios C., Van den Broek J. A., Schott M.K., Kalbitzer H.R., Becker K., Schubert D. and Schirmer R.H., Denaturation and reactivation of dimeric human glutathione reductase--an assay for folding inhibitors, Eur J Biochem, 245(2) (1997) 273-282.
[46] Kasozi D.M., Gromer S., Adler H., Zocher K., Rahlfs S., Wittlin S., Fritz-Wolf K., Schirmer R.H. and Becker K., The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue, Redox Rep, 16(4) (2011) 154-165.

Details

Primary Language

English

Subjects

Structural Biology

Journal Section

Research Article

Authors

Muhammet Karaman ^*
0000-0002-0155-3390
Türkiye

Publication Date

December 29, 2020

Submission Date

January 21, 2020

Acceptance Date

June 29, 2020

Published in Issue

Year 2020 Volume: 41 Number: 4

DOI

https://doi.org/10.17776/csj.678045

IZ

https://izlik.org/JA53HC24DY

Cite

RIS / Bibtex

APA

Karaman, M. (2020). Molecular Insight of the Possible Inhibition Mechanism of Therapeutic Cephalosporin Derivatives against Human Glutathione Reductase Enzyme. Cumhuriyet Science Journal, 41(4), 747-755. https://doi.org/10.17776/csj.678045