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Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors

[ Vol. 19 , Issue. 5 ]

Author(s):

Sachin Jangra, Gayathri Purushothaman, Kapil Juvale, Srimadhavi Ravi, Aishwarya Menon, Vijay Thiruvenkatam and Sivapriya Kirubakaran*   Pages 376 - 382 ( 7 )

Abstract:


Background & Objective: Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori. Inosine 5′-monophosphate dehydrogenase (IMPDH), a metabolic enzyme plays a significant role in cell proliferation and cell growth. It catalyses guanine nucleotide synthesis. IMPDH enzyme has been exploited as a target for antiviral, anticancer and immunosuppressive drugs. Recently, bacterial IMPDH has been studied as a potential target for treating bacterial infections. Differences in the structural and kinetic parameters of the eukaryotic and prokaryotic IMPDH make it possible to target bacterial enzyme selectively.

Methods: In the current work, we have synthesised and studied the effect of substituted 3-aryldiazenyl indoles on Helicobacter pylori IMPDH (HpIMPDH) activity. The synthesised molecules were examined for their inhibitory potential against recombinant HpIMPDH.

Results: In this study, compounds 1 and 2 were found to be the most potent inhibitors amongst the database with IC50 of 0.8 ± 0.02µM and 1 ± 0.03 µM, respectively.

Conclusion: When compared to the most potent known HpIMPDH inhibitor molecule C91, 1 was only four-fold less potent and can be a good lead for further development of selective and potent inhibitors of HpIMPDH.

Keywords:

Helicobacter pylori, Inosine 5 ′-monophosphate dehydrogenase (IMPDH), Indole, Azo compounds, Enzymatic studies, Bacteria.

Affiliation:

Chemistry, Indian Institute of Technology Gandhinagar, Gujarat, Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat, Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat, Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat

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