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Current Topics in Medicinal Chemistry

Author(s): Sachin Jangra, Gayathri Purushothaman, Kapil Juvale, Srimadhavi Ravi, Aishwarya Menon, Vijay Thiruvenkatam and Sivapriya Kirubakaran*

DOI: 10.2174/1568026619666190227212334

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

Page: [376 - 382] Pages: 7

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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.

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