Anti-Helicobacter pylori activity and Structure-Activity Relationship study of 2-Alkylthio-5-(nitroaryl)-1,3,4-thiadiazole Derivatives

Document Type: Research article

Authors

1 Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, IR Iran.

2 1- Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, IR Iran. 2- Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz 71345, IR Iran.

3 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, IR Iran.

4 Department of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, IR Iran.

5 Department of Microbiology, Faculty of Sciences, University of Tehran, IR Iran.

6 1- Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, IR Iran. 2- Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, IR Iran.

Abstract

Nitro-containing heteroaromatic derivatives structurally related to nitroimidazole (Metronidazole) are being extensively evaluated against Helicobacter pylori isolates. On the other hand, 1,3,4-thiadiazole derivatives have also demonstrated promising antibacterial potential. In present study, we evaluated anti-H. pylori activity of novel hybrid molecules bearing nitroaryl and 1,3,4-thiadiazole moieties.
Anti-H. pylori activity of novel 5-(5-nitroaryl)-1,3,4-thiadiazole derivatives bearing different bulky alkylthio side chains at C-2 position of thiadiazole ring, were assessed against three different metronidazole resistant H. pylori isolates by paper disk diffusion method.
Most of the compounds demonstrated moderate to strong inhibitory response especially at 25 μg/disk. The structure-activity relationship study of the compounds demonstrated that introduction of different alkylthio moieties at C-2 position of thiadiazole ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring. The promising compound of this scaffold, bearing 1-methyl-5-nitroimidazole moiety at C-5 and α-methylbenzylthio side chain at C-2 position of thiadiazole ring, showed strong inhibitory response against metronidazole resistant H. pylori isolates at 12.5 μg/disk (the inhibition zone diameter at all evaluated concentrations (12.5-100 μg/disk) is > 50 mm).
Novel 5-(5-nitroaryl)-1,3,4-thiadiazole scaffold bearing different C-2 attached thio-pendant moieties with promising anti-H. pylori potential were identified. Among different nitroheterocycles, 5-nitrofuran and 5-nitroimidazole moieties were preferable for the substitution at C-5 position of 1,3,4-thiadiazole ring. Introduction of different alkylthio side chains at C-2 position of central ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring.

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