Int J Pharma Res Health Sci. 2019; 7 (6): 3111-16
3111
IIIIIIIII© International Journal of Pharma Research and Health Sciences. All rights reserved
DOI:10.21276/ijprhs.2019.06.08
Kumar Sambhav et al. CODEN (USA)-IJPRUR, e-ISSN: 2348-6465
Original Article
In-silico Design of Covalently Bonding Catechol based
Urease Inhibitors as Potential Candidates for
Treatment of Helicobacter pylori Infection
Kumar Sambhav Chopdar
1
, Ganesh Chandra Dash
2
, Pranab Kishor Mohapatra
3
, Binata
Nayak
4
, Mukesh Kumar Raval
5, #, *
1
Department of Zoology, Rajendra College, Balangir, Odisha 767002, India.
2
Department of Chemistry, APS College, Roth, Balangir, Odisha 767061, India.
3
Department of Chemistry, CV Raman College of Engineering, Bhubaneswar, Odisha 752054, India.
4
School of Life Sciences, Sambalpur University, Sambalpur, Odisha 768019, India.
5
Department of Chemistry, Gangadhar Meher University, Sambalpur, Odisha 768004, India.
ARTICLE INFO ABSTRACT
______
1. INTRODUCTION
Importance of the role of urease in microbial pathogenicity
in general and Helicobacter pylori (H. Pylori) induced
gastro-duodenal infection in particular is well established [1-
7]. Urease inhibitors may serve as a drug candidate for
remedy to urease related pathogenic conditions. In spite of
International Journal of Pharma Research and Health Sciences
Available online at www.pharmahealthsciences.net
Received: 19 Nov 2019
Accepted: 29 Dec 2019
Corresponding author *
Mukesh Kumar Raval
Department of Chemistry, GangadharMeher University,
Sambalpur, Odisha 768004, India.
# Present Address: Stone Building, Opposite Mission School,
Balangir, Odisha 767001, India
E-mail ID: mraval@yahoo.com
Design and synthesis of novel urease inhibitors are gaining importance now days with
specific context as a remedy to Helicobacter pylori infection. Toxicity and hydrolytic profile of
urease inhibitors are deciding factors for success of in vivo and clinical trials. An attempt is
made to design covalently bound inhibitors through C-S bond between aromatic ring carbon
and sulfur (SG) atom of Cys321 in H. pylori urease, 1e9y. Catechol and p-benzoquinone are
known to form such covalent linkage. The catechol ring substituted with an alkyl chain
ending with a functional group with potentiality to bind to Ni (II) atoms are designed in silico.
These designed inhibitors at one end form covalent linkage at Cys321 at the mouth of the
active site while link to Ni (II) deep down the site on the other end. These types of molecules
with both ends sticky may serve as highly potent inhibitors of urease hence potent drug
candidates against H. pylori infection. The docking scores and acceptable ADMET
parameters are also considered in the design. The compounds may serve as novel covalent
inhibitors with high specificity, high potency and low toxicity.
Key words: Urease inhibitors, covalently bound ligands, Helicobacter pylori, Catechol.