Synthesis, Characterization, and Molecular Docking Against a Receptor Protein FimH of Escherichia coli (4XO8) of Thymidine Derivatives

  • Asraful Alam University of Chittagong
  • Mohammed Anowar Hosen University of Chittagong
  • Anowar Hosen University of Dhaka
  • Yuki Fujii Nagasaki International University
  • Yasuhiro Ozeki Yokohama City University
  • Sarkar Mohammad Abe Kawsar University of Chittagong
Keywords: Thymidine, synthesis, Escherichia coli, molecular docking, DFT, inhibitor, lectin protein (FimH)

Abstract

Abstract. Thymidine is known as a progenitor of nucleosides that have significant biological activity. The widening importance of nucleoside derivatives as unrivaled potential antimicrobial and therapeutic agents has attracted contemplation to the synthesis of thymidine derivatives. In the present study, thymidine was treated with various acyl halides to produce 5ʹ-O-acyl thymidine derivatives by direct acylation method with an excellent yield. To obtain newer products for antimicrobial assessment studies, the 5ʹ-O-thymidine derivatives were further modified into three series of 3ʹ-O-acyl thymidine derivatives containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were elucidated by analyzing their physicochemical, elemental, and spectroscopic data. Additionally, the X-ray powder diffraction (XRD) of these acylated products was studied. For the computational investigation, we have selected eight synthesized thymidine derivatives, which have notable antibacterial activity, and performed molecular docking against bacterial lectin protein FimH of Escherichia coli (4XO8) to suggest a potent inhibitor against bacterial function. Molecular docking was performed using AutoDock Vina to calculate the binding affinities and interactions between the antibacterials and the FimH E. coli (4XO8). It was found that the selected thymidine derivatives have strongly interacted mainly with Tyr48, Tyr137, Asp140, Arg98, Gln133, Phe1, Asn23, Asn135, Lys76, Asp47, Ile13, and Ile52 residues. In silico pharmacokinetic properties were also predicted to search their absorption, metabolism, excretion, and toxicity. This computational examination showed that these thymidine derivatives might be used as potential inhibitors against the promising antibacterial activity for future studies.

 

Resumen. Se prepararon varios derivados 5ʹ-O-acil timidínicos por acilación directa con rendimientos excelentes que fueron transformados en tres series de derivados 3ʹ-O-acil timidínicos con una amplia variedad de funcionalidades. Estos compuestos fueron la base de un estudio de docking dirigido a la lectina bacteriana FimH de Escherichia coli (4XO8) con la finalidad de proponer un inhibidor contra esta función bacteriana.

Author Biographies

Asraful Alam, University of Chittagong

Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science

Mohammed Anowar Hosen, University of Chittagong

Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science

Anowar Hosen, University of Dhaka

Centre for Advanced Research in Sciences

Yuki Fujii, Nagasaki International University

Laboratory of Functional Morphology, Graduate School of Pharmaceutical Sciences

Yasuhiro Ozeki, Yokohama City University

Laboratory of Glycobiology and Marine Biochemistry, Department of Life and Environmental System Science, Graduate School of NanoBiosciences

Sarkar Mohammad Abe Kawsar, University of Chittagong

Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science

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Published
02-22-2021