Synthesis of new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives as anti-MRSA and anti-H. pylori agents

Abstract

In this work, we have synthesized twenty five new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives bearing an aryl or heteroaryl methylene group on position 5 of thiazolidinone and evaluated their antimicrobial activity against Gram-positive and -negative bacteria as well as three metronidazole resistant Helicobacter pylori strains. Most of the compounds were very potent towards tested Gram-positive bacteria and showed an antibacterial efficacy substantially greater than ampicillin as the reference drug. However, no effectiveness was observed for the Gram-negative microorganisms. The compounds 9, 20 and 29 exhibited strong antimicrobial activity against Helicobacter pylori strains (inhibition zone > 30 mm) in 100 μg/disc and (inhibition zone > 20 mm) in 50 μg/disc. Taking these findings together, it seems that these potent antibacterial derivatives could be considered as promising agents for developing new anti-infectious drugs against microorganisms resistant to currently available antibiotics.

Keywords: 4-Thiazolidinone; Antibacterial activity; Gram-positive; Helicobacter pylori; Nitrofuran; Thiadiazole.

Fig. 1

The design of target compounds by incorporating 4-thiazolidinone, 1,3,4-thiadiazole and 5-nitrofuran rings

Scheme 1

Synthesis of 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives 7–31. Reagents and conditions: a) Thiosemicarbazide, Ethanol, Hydrochloric Acid, Reflux, 1.5 h, b) Ferric Ammonium Sulfate, Water, Reflux 24 h, c) Chloroacetyl Chloride, Toluene, 80–90 °C, 3 h, d) Ammonium thiocyanate, Ethanol, reflux, 3 h, e) ArCHO, Sodium Acetate, Acetic Acid, Reflux, 24 h