Title of article :
Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents
Author/Authors :
Faghih-Mirzaei, Ehsan Department of Medicinal Chemistry - Faculty of Pharmacy - Kerman University of Medical Sciences, Kerman, Iran , Seifi, Mohammad Department of Chemistry - Faculty of Sciences - Islamic Azad University of Najafabad, Najafabad, Isfahan, Iran , Abaszadeh, Mehdi Pharmaceutics Research Center - Institute of Neuropharmacology - Kerman University of Medical Sciences, Kerman, Iran , Zomorodian, Kamiar Department of Medical Mycology and Parasitology - Basic Sciences in Infectious Diseases Research Center - School of Medicine - Shiraz University of Medical Sciences, Shiraz, Iran , Helali, Helia Department of Medical Mycology and Parasitology - Basic Sciences in Infectious Diseases Research Center - School of Medicine - Shiraz University of Medical Sciences, Shiraz, Iran
Abstract :
A novel one-pot two step tandem reaction for the synthesis of indolizine-1-carbonitrile
derivatives (5a-i) was identified. The route comprises 1,3-dipolar cycloaddition reaction of
aromatic aldehyde derivatives (1a-i), malononitrile (2) and 1-(2-(4-bromophenyl)-2-oxoethyl)-
2-chloropyridin-1-ium (4) under ultrasound irradiation at room temperature in the presence of
triethylamine at acetonitrile. The product compounds were tested against bacteria and fungi. It
was revealed that compound 5b had the most antifungal activity (range MICs = 8–32 μg/mL)
and compound 5g had the most antibacterial activity (range MICs = 16–256 μg/mL). Molecular
docking of compounds (5a-i) into fungal 14α-demethylase and bacterial protein tyrosine
phosphatase active sites were also performed and probable binding mode of compounds 5b and
5g were determined.
Keywords :
Molecular docking , Antibacterial activity , Antifungal activity , Ultrasound irradiation , 1,3-Dipolar cycloaddition , Indolizine-1-carbonitriles
