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Molecular docking studies on analogues of quercetin with d-alanine:d-alanine ligase of Helicobacter pylori

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Abstract

Helicobacter pylori (Hp) is a human pathogen associated with myriad of diseases such as gastritis, peptic ulceration, piles and gastric cancer. The resistance of Hp against antimicrobial agents has increased just as that of other pathogens worldwide, thus emphasizing an urgent need for developing new antibacterial agents. The d-alanine:d-alanine ligase (Ddl, EC 6.3.2.4) has been considered as a putative antimicrobial drug target and a lot of inhibitor screening efforts have been made. Quercetin, a member of the flavonoids, characterized by a flavone nucleus composed of two benzene rings linked through a heterocyclic pyrone ring is reported to possess antibacterial activity against H. pylori Ddl (HpDdl) enzyme. In this milieu, we have performed molecular docking analysis of quercetin and its analogues at the active site of HpDdl. Some of the screened compounds showed better affinity and interaction with HpDdl enzyme. The docking analysis and absorption, distribution, metabolism and toxicity study forward few of them as plausible lead molecule or a novel class of drugs with enhanced pharmacological properties.

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Acknowledgments

The authors thank Department of Biotechnology (DBT), Government of India for providing Bioinformatics Infrastructure Facility and Vice-Chancellor, Tezpur University for support in carrying out this research work. Rocktotpal Konwarh also acknowledges the receipt of his Senior Research Fellowship from DBT, New Delhi.

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Correspondence to Salam Pradeep Singh or Niranjan Karak.

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Singh, S.P., Konwarh, R., Konwar, B.K. et al. Molecular docking studies on analogues of quercetin with d-alanine:d-alanine ligase of Helicobacter pylori . Med Chem Res 22, 2139–2150 (2013). https://doi.org/10.1007/s00044-012-0207-7

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Keywords

  • Antimicrobial agent
  • Antibacterial activity
  • Flavonoids
  • Molecular docking