PASS prediction, molecular docking and pharmacokinetic studies of acyl substituted bioactive galactopyranoside esters as antibacterial agents

Authors

  • Sarkar Mohammad Abe Kawsar Lab of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong
  • Mebarka Ouassaf Group of Computational and Medicinal Chemistry, Laboratory of Molecular Chemistry and Environment Laboratory, University of Biskra, Biskra
  • Samir Chtita Laboratory of Physical Chemistry of Materials, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, BP7955 Sidi Othmane, Casablanca
  • Aishi Barua Jui Lab of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong
  • Salah Belaidi Group of Computational and Medicinal Chemistry, Laboratory of Molecular Chemistry and Environment Laboratory, University of Biskra, Biskra

Keywords:

methyl-β-D-galactopyranoside (MDG), molecular docking, antibacterial agents, pharmacokinetic, PASS

Abstract

Currently, methyl-β-D-galactopyranoside (MDG) esters have become a focus of attention due to their promising biological and pharmacokinetic properties and could be a good choice in unraveling the global issue of pathogenic multidrug resistance. Structural modification of MDG can improve its mode of biological activity. In line with these efforts, a series of previously synthesized MDG esters were designed and evaluated by Prediction of Activity Spectra for Substances (PASS), molecular docking simulation, and pharmacokinetic depiction. Encouraging PASS activity was observed for several aliphatic and aromatic MDG esters, and antibacterial efficacy was more promising than other features. In support, molecular docking studies were performed against the macrolide phosphotransferase enzyme MPH to identify a potential allosteric binding site for these esters. Molecular docking indicated that the shape of the MDG esters and their ability to form multiple electrostatic and hydrogen bonds with the active site corresponds to the binding modes of other minor-groove binders. Pharmacokinetic predictions were also performed to evaluate the absorption, metabolism, and toxic properties of MDG esters. These findings demonstrate that MDG esters are promising for use as biocompatible antibacterial agents in the future.

References

Tyers, M.; Wright, G. D. Drug combinations: A strate-gy to extend the life of antibiotics in the 21st Century. Nature Rev. Microbiol. 2019, 17 (3), 144–155.

https://doi.org/10.1038/s41579-018-0141-x.

Amin, M. R.; Yasmin, F.; Hosen, M. A.; Dey, S.; Mahmud, S.; Saleh, M. A.; Hasan, I.; Fujii, Y.; Yama-da, M.; Ozeki, Y.; Kawsar, S. M. A. Synthesis, antimi-crobial, anticancer, PASS, molecular docking, molecu-lar dynamic simulations and pharmacokinetic predic-tions of some methyl β-D-galactopyranoside analogs. Molecules 2021, 26 (22), 1–25.

https://doi.org/10.3390/molecules26227016.

Amin, M. R.; Yasmin, F.; Dey, S.; Mahmud, S.; Saleh, Emran, T. B.; Hasan, I.; Rajia, S.; Ogawa, Y.; Fujii, Y.; Yamada, M.; Ozeki, Y.; Kawsar, S. M. A. Methyl β-D-galactopyranoside esters as potential inhibitors for SARS-CoV-2 protease enzyme: synthesis, antimicro-bial, PASS, molecular docking, molecular dynamics simulations and quantum computations. Glycoconju-gate J. 2021, 38 (5), 1–30. https://doi.org/10.1007/s10719-021-10039-3.

Tong, S. Y.; David, J. S.; Eichenberger, E.; Holland, T. L.; Fowler, V. G. J. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifesta-tions, and management. Clin. Microbiol. Rev. 2015, 28 (3), 603–661. https://doi.org/10.1128/cmr.00134-14.

Noble, S. M.; Gianetti B. A.; Witchley, J. N. Candida albicans cell-type switching and functional plasticity in the mammalian host. Nat. Rev. Microbiol. 2017, 15 (2), 96–108. https://doi.org/10.1038/nrmicro.2016.157.

Hosen, M. A.; Alam, A.; Islam, M.; Fujii, Y.; Ozeki, Y.; Kawsar, S. M. A. Geometrical optimization, PASS prediction, molecular docking, and in silico ADMET studies of thymidine derivatives against FimH adhesin of Escherichia coli. Bulg. Chem. Commun. 2021, 53 (3), 327–342. http://doi.org/10.34049/bcc.53.3.5375.

Golkar, T.; Zeliński, M.; Berghuis, A. B. Look and outlook on enzyme-mediated macrolide resistance. Front. Microbiol. 2018, 9 (1942), 1–15.

https://doi.org/10.3389/fmicb.2018.01942.

Noreen, N. K.; Daniel, C. J.; Zarek, S. S. Synthesis, kinetics and inhibition of Escherichia coli Heptosyl-transferase I by monosaccharide analogues of Lipid A. Bioorg. Med. Chem. Lett. 2018, 28 (4), 594–600. https://doi.org/10.1016/j.bmcl.2018.01.040.

Kawsar, S. M. A.; Faruk, M. O.; Rahman, M. S.; Fujii, Y.; Ozeki Y. Regioselective synthesis, characteriza-tion, and antimicrobial activities of some new mono-saccharide derivatives. Sci. Pharm. 2014, 82 (1), 1–20. https://doi.org/10.3797/scipharm.1308-03.

Misbah, M. M. H.; Ferdous, J.; Bulbul, M. Z. H.; Chowdhury, T. S.; Dey, S.; Hasan, I.; Kawsar, S. M. A. Evaluation of MIC, MBC, MFC and anticancer ac-tivities of acylated methyl β-D-galactopyranoside Es-ters. Int. J. Biosci. 2020, 16 (4), 299–309.

https://doi.org/10.12692/ijb/16.4.299-309.

Mirajul, M. I.; Arifuzzaman, M.; Monjur, M. R.; Atiar, M. R.; Kawsar, S. M. A. Novel methyl 4,6-O-benzylidene--D-glucopyranoside derivatives: synthe-sis, structural characterization and evaluation of anti-bacterial activities. Hacettepe J. Biol. Chem. 2019, 47 (2), 153–164. https://doi.org/10.15671/hjbc.622038.

Yasmin, F.; Amin, M. R.; Hosen, M. A.; Bulbul, M. Z. H.; Dey, S.; Kawsar, S. M. A. Monosaccharide deriva-tives: synthesis, antimicrobial, PASS, antiviral and mo-lecular docking studies against SARS-COV-2 Mpro in-hibitors. Cellu. Chem. Technol. 2021, 55 (5-6), 477–499. https://doi.org/0.1126/science.1059820

Bertozzi C. R.; Kiessling, L. L. Chemical Glycobiolo-gy. Science 2001, 291 (5512), 2357–2364.

https://doi.org/10.1126/science.1059820.

Chen S.; Fukuda, M. Cell type-specific roles of carbo-hydrates in tumor metastasis. Meth. Enzymol. 2006, 416, 371–380. https://doi.org/10.1016/S0076-6879(06)16024-3.

Kawsar, S. M. A.; Hamida, A. A.; Sheikh, A. U.; Hossain, M. K.; Shagir, A. C.; Sanaullah, A. F. M.; Manchur, M. A.; Imtiaj, H.; Ogawa, Y.; Fujii, Y.; Koide, Y.; Ozeki, Y. Chemically modified uridine molecules incorporating acyl residues to enhance anti-bacterial and cytotoxic activities. Int. J. Org. Chem. 2015, 5 (4), 232–245. https://doi.org/10.4236/ijoc.2015.54023.

Shagir, A. C.; Bhuiyan, M. M. R.; Ozeki Y.; Kawsar, S. M. A. Simple and rapid synthesis of some nucleo-side derivatives: structural and spectral characteriza-tion. Curr. Chem. Lett. 2016, 5 (2), 83–92.

https://doi.org/10.5267/j.ccl.2015.12.001.

Kawsar, S. M. A.; Islam, M.; Jesmin, S.; Manchur, M. A.; Hasan, I.; Rajia, S. Evaluation of the antimicrobial activity and cytotoxic effect of some uridine deriva-tives. Int. J. Biosci. 2018, 12 (6), 211–219. https://doi.org/10.12692/ijb/12.6.211-219.

Rana, K. M.; Ferdous, J.; Hosen, A.; Kawsar, S. M. A. Ribose moieties acylation and characterization of some cytidine analogs. J. Sib. Fed. Univ. Chem. 2020, 13 (4), 465–478. https://doi.org/10.17516/1998-2836-0199.

Bulbul, M. Z. H.; Chowdhury, T. S.; Misbah, M. M. H.; Ferdous, J.; Dey, S.; Hasan, I.; Fujii, Y.; Ozeki, Y.; Kawsar, S. M. A. Synthesis of new series of pyrimi-dine nucleoside derivatives bearing the acyl moieties as potential antimicrobial agents. Pharmacia 2021, 68 (1), 23–34. https://doi.org/10.3897/pharmacia.68.e56543.

Devi, S. R.; Jesmin, S.; Rahman, M.; Manchur, M. A.; Fujii, Y.; Kanaly, R. A.; Ozeki, Y.; Kawsar, S. M. A. Microbial efficacy and two step synthesis of uridine derivatives with spectral characterization. Acta Pharm. Sci. 2019, 57 (1), 47–68.

https://doi.org/10.23893/1307-2080.APS.05704.

Arifuzzaman, M.; Islam, M. M.; Rahman, M. M.; Mo-hammad, A. R.; Kawsar, S. M. A. An efficient ap-proach to the synthesis of thymidine derivatives con-taining various acyl groups: characterization and anti-bacterial activities. ACTA Pharm. Sci. 2018, 56 (4), 7–22. https://doi.org/10.23893/1307-2080.APS.05622.

Maowa, J.; Alam, A.; Rana, K. M.; Dey, S.; Hosen, A.; Fujii, Y.; Hasan, I.; Ozeki, Y.; Kawsar, S. M. A. Syn-thesis, characterization, synergistic antimicrobial prop-erties and molecular docking of sugar modified uri-dine derivatives. Ovidius Univ. Ann. Chem. 2021, 32 (1), 6–21. https://doi.org/10.2478/auoc-2021-0002.

Bulbul, M. Z. H.; Hosen, M. A.; Ferdous, J.; Chow-dhury, T. S.; Misbah, M. M. H.; Kawsar, S. M. A. Thermochemical, DFT study, physicochemical, mo-lecular docking and ADMET predictions of some modified uridine derivatives. Int. J. New Chem. 2021, 8 (1), 88–110. https://doi.org/10.22034/ijnc.2020.131337.1124.

Maowa, J.; Hosen, M. A.; Alam, A.; Rana, K. M.; Fu-jii, Y.; Ozeki, Y.; Kawsar, S. M. A. Pharmacokinetics and molecular docking studies of uridine derivatives as SARS- CoV-2 Mpro inhibitors. Phys. Chem. Res. 2021, 9 (3), 385–412. https://doi.org/10.22036/pcr.2021.264541.1869.

Alam, A.; Hosen, M. A.; Hosen, A.; Fujii, Y.; Oze-ki, Y.; Kawsar, S. M. A. Synthesis, characterization, and molecular docking against a receptor protein FimH of Escherichia coli (4XO8) of thymidine derivatives. J. Mex. Chem. Soc. 2021, 65 (2), 256–276.

https://doi.org/10.29356/jmcs.v65i1.1464.

Kawsar, S. M. A.; Hosen, M. A. An optimization and pharmacokinetic studies of some thymidine deriva-tives. Turkish Comp. Theo. Chem. 2020, 4 (2), 59–66.

https://doi.org/10.33435/tcandtc.718807.

Kawsar, S. M. A.; Hosen, M. A.; Fujii, Y.; Ozeki, Y. Thermochemical, DFT, molecular docking and phar-macokinetic studies of methyl β-D-galactopyranoside esters. J. Comput. Chem. Mol. Model. 2020, 4 (4), 452–462. https://doi.org/10.25177/JCCMM.4.4.RA.10663.

Kumaresan, S.; Senthilkumar, V.; Stephen, A. B. S. GC-MS analysis and PASS-assisted prediction of bio-logical activity spectra of extract of Phomopsis sp. iso-lated from Andrographis paniculata. World J. Pharm. Res. 2015, 4 (1), 1035–1053.

Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.; Izmaylov, A. F.; Sonnenberg, J. L.; Wil-liams-Young, D.; Ding, F.; Lipparini, F.; Egidi, F.; Go-ings, J.; Peng, B.; Petrone, A.; Henderson, T.; Rana-singhe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.; Montgomery, J. A., Jr; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov, V. N.; Keith, T. A.; Ko-bayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J. Gaussian 16, Revision C.01; Gaussian, Inc., Wallingford CT, USA, 2016.

Laskowski, R. A.; Swindells, M. B. LigPlot+: multiple ligand–protein interaction diagrams for drugn discov-ery. J. Chem. Inf. Model. 2011, 51 (10), 2778–2786. https://doi.org/10.1021/ci200227u.

Marvig, R. L.; Søndergaard, M. S. R.; Damkiær, S.; Høiby, N.; Johansen, H. K.; Molin, S.; Jelsbak, L. Mu-tations in 23S RRNA confer resistance against Azithromycin in Pseudomonas aeruginosa. Antimi-crob. Agents Chemother. 2012, 56 (8), 4519–4521.

https://doi.org/10.1128/AAC.00630-12.

Fong, D. H.; Burk, D. L.; Blanchet, J.; Yan, A. Y.; Berghuis, A. M. Structural basis for kinase-mediated macrolide antibiotic resistance. Structure 2017, 25 (5), 750–761. https://doi.org/10.1016/j.str.2017.03.007.

Marvin, ChemAxon.

https://chemaxon.com/products/marvin.

Frank, J. The ribosome–a macromolecular machine par excellence. Chem. Biol. 2000, 7 (6), R133–141.

https://doi.org/10.1016/S1074-5521(00)00127-7.

Pires, D. E. V.; Blundell, T. L.; Ascher, B. D. pkCSM: Predicting small-molecule pharmacokinetic and toxici-ty properties using graph-based signatures. J. Med. Chem. 2015, 58 (9), 4066–4072.

https://doi.org/10.1021/acs.jmedchem.5b00104.

Fouedjou, R. T.; Chtita, S.; Bakhouch, M.; Belaidi, S.; Ouassaf, M.; Djoumbissie, L. A.; Tapondjou, L. A.; Qais, F. A. Cameroonian medicinal plants as potential candidates of SARS-CoV-2 inhibitors. J. Biomol. Struct. Dyn. 2021, 28, 1–15.

https://doi.org/10.1080/07391102.2021.1914170.

A. Alam, K. M. Rana, M. A. Hosen, S. Dey, B. Bezba-ruah, S. M. A. Kawsar, Modified thymidine deriva-tives as potential inhibitors of SARS-CoV: PASS, in vitro antimicrobial, physicochemical and molecular docking studies, Phys. Chem. Res. 2022, 10 (3), 391–409. https://doi.org/10.22036/PCR.2022.317494.1996 .

Ouassaf, M.; Belaidi, S.; Mogren, M.; Mogren, A.; Chtita, S.; Khan, S.; Htar, T. A. Docking-scoring ap-proach to identify effective antiviral 2,5-diaminoBenzophenone derivatives against the main protease of SARS-CoV-2. J. King Saud Univ. Sci. 2021, 33, 101352. https://doi.org/10.1016/j.jksus.2021.101352.

Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development. Adv. Drug Deliv. Rev. 2001, 46, 3–25. https://doi.org/10.1016/s0169-409x(00)00129-0.

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Published

2022-05-17

How to Cite

Kawsar, S. M. A., Ouassaf, M., Chtita, S., Jui, A. B., & Belaidi, S. (2022). PASS prediction, molecular docking and pharmacokinetic studies of acyl substituted bioactive galactopyranoside esters as antibacterial agents. Macedonian Journal of Chemistry and Chemical Engineering, 41(1). Retrieved from https://mjcce.org.mk/index.php/MJCCE/article/view/2403

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Theoretical Chemistry