Synthesis and Anti-Helicobacter pylori Activity of 4-(Coumarin-3-yl)thiazol-2-ylhydrazone Derivatives Franco Chimenti, a Bruna Bizzarri, a * Adriana Bolasco, a Daniela Secci, a Paola Chimenti, a Arianna Granese, a Simone Carradori, a Melissa D’Ascenzio, a M. Maddalena Scaltrito, b and Francesca Sisto b a Dipartimento di Chimica e Tecnologie del Farmaco, University ‘‘La Sapienza,’’ P.le A. Moro 5, 00185 Rome, Italy b Dipartimento di Sanita ` Pubblica-Microbiologia-Virologia, Universita ` degli Studi di Milano, via Pascal 36, 20133 Milan, Italy *E-mail: bruna.bizzarri@uniroma1.it Received January 13, 2010 DOI 10.1002/jhet.464 Published online 20 August 2010 in Wiley Online Library (wileyonlinelibrary.com). A novel class of coumarin-thiazole conjugated systems (1–31) were synthesized by Hantzsch conden- sation between a-bromo-3-acetyl coumarin and several thiosemicarbazone intermediates. This scaffold was also evaluated for selective antibacterial activity against 20 isolates of H. pylori clinical strains, including four metronidazole resistant ones. J. Heterocyclic Chem., 47, 1269 (2010). INTRODUCTION Helicobacter pylori are spiral-shaped Gram-negative bacteria with polar flagella that live near the surface of the human gastric mucosa. They have evolved specific mechanisms to avoid the bactericidal acid environment in the gastric lumen to survive near, to attach to, and to communicate with the human gastric epithelium and host immune system. This interaction sometimes results in severe gastric pathology. In fact, H. pylori infection is indeed the most known risk factor for the development of gastroduodenal ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori infections are difficult to cure and success- ful treatment generally requires the simultaneous som- ministration of several antibacterial agents. Antibiotic resistance has resulted in unsatisfactory eradication with dual and now triple therapy in many countries. Newer antibiotics and changes in dosing and duration of therapy may overcome resistant strains but may only provide limited improvement in eradication rates [1–3]. In our previous works [4,5] and from the analysis of the structure of natural coumarins reported as potent anti-H. pylori agents [6], we have pointed out that the coumarin ring might play an important role in determin- ing activity and seemed to be crucial for the selective antimicrobial activity of such compounds. Recently, we have synthesized and chemically and biologically char- acterized some new conjugated coumarin-thiazole sys- tems, which were endowed with interesting industrial properties and especially antimicrobial activity on H. pylori clinical strains [7]. Furthermore, interest in these structures has renewed due to the recent discovery of their promising antibacte- rial, antifungal, and antimycobacterial activity [8–11]. Moving from these indications, in this report we described the synthesis and selective antimicrobial evalu- ation of a new series of 4-(coumarin-3-yl)thiazol-2-ylhy- drazone derivatives which differ for the electronic and steric characteristics on the hydrazone nitrogen (aliphatic chains, cycloaliphatic moiety, and heterocyclic rings). RESULTS AND DISCUSSION The coumarin-thiazole derivatives (1–30) were pre- pared in high yields (69–99%) according to a protocol V C 2010 HeteroCorporation November 2010 1269