Synthesis and biological evaluation of novel benzyl piperazine derivatives of 5-(5-nitroaryl)-1,3,4-thiadiazoles as Anti-Helicobacter pylori agents.
OBJECTIVE
Helicobacter pylori is recognized as the main cause of gastritis and gastroduodenal ulcers and classified as class 1 carcinogen pathogen. Different 1,3,4-thiadiazole derivatives bearing 5-nitroaryl moiety have been shown considerable anti- H. pylori activity. In attempt to find new and potent derivatives of described scaffold, a new series of 1-(substituted benzyl)-4-(5-(5-nitroaryl-2-yl)-1,3,4-thiadiazol-2-yl)piperazine derivatives were synthesized and evaluated against three metronidazole-resistant isolates of H. pylori using paper disk diffusion bioassay test.


METHODS
The title compounds were prepared through the reaction of 1-(5-(5-nitroaryl-2-yl)-1,3,4-thiadiazol-2-yl) piperazine 5a-b and substituted benzyl chloride in DMF. The inhibitory activity of the new derivatives 6a-q against three metronidazole-resistant isolates of H. pylori was evaluated by the disc diffusion method and compared with the commercially available standard drug metronidazole.


CONCLUSIONS
The results of SAR study indicated that the potency and anti-H. pylori activity profile of synthesized derivatives is mainly attributed to the substituted nitroaryl moiety at the C-5 position of 1,3,4-thiadiazole ring. Most of 1,3,4-thiadiazole derivatives bearing 5-nitrofuran moiety at C-5 position of central thiadiazole ring, demonstrated more promising anti-H. pylori than the 5-nitrothiophen counterpart.


CONCLUSIONS
The most potent nitrofuran derivative containing 3-methoxybenzyl piperazine pendant at the C-2 position of 1,3,4-thiadiazole ring (compound 6i), demonstrated strong anti-H. pylori potential at studied concentrations 100-25 μg/disk (IZD > 20 mm) against all studied metronidazole- resistant isolates of H. pylori.
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran. ashafiee@ams.ac.ir.
Negar
N
Mohammadhosseini
Parastoo
P
Saniee
Ameneh
A
Ghamaripour
Hassan
H
Aryapour
Farzaneh
F
Afshar
Najmeh
N
Edraki
Farideh
F
Siavoshi
Alireza
A
Foroumadi
Abbas
A
Shafiee