Synthesis of certain new fused pyranopyrazole and pyranoimidazole incorporated into 8-hydroxyquinoline through a sulfonyl bridge at position 5 with evaluation of their in-vitro antimicrobial and antiviral activities
Emad M. Kassem1, Eslam R. El-Sawy2, Howaida I. Abd-Alla2, Adel H. Mandour2, Dina Abdel-Mogeed1, Mounir M. El-Safty3
1 Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza, Egypt
2 Department of Chemistry of Natural Compounds, National Research Centre, Dokki, Giza, Egypt
3 Central Laboratory for Evaluation of Veterinary Biologics, Abbassia, Cairo, Egypt
Eslam R. El-Sawy
Department of Natural Compounds Chemistry, National Research Centre, 12311 Dokki, Giza
Source of Support: None, Conflict of Interest: None
Background and objectives
Heterocyclic systems with a quinoline nucleus display a wide spectrum of biological activities such as antimicrobial and antiviral activities. The aim of the present study was the synthesis of new fused pyranopyrazoles, 5a-e and 6a-e, and pyranoimidazoles, 10a-e and 11a-e, incorporated to 8-hydroxyquinoline through a sulfonyl bridge at position 5 and evaluation of their antimicrobial and antiviral activities.
The synthesis of the titled quinoline derivatives was achieved through cyclization of 8-hydroxyquinoline-5-sulfonyl chloride (1) with 2º-acetyl-2-cyanoacetohydrazide, 2-cyanoacetic acid hydrazide, and 3-amino-5-pyrazolone to afford 2, 3, and 4, respectively. Moreover, reaction of 1 with glycine gives 7, which on heterocyclization with ammonium thiocyanate yielded the 2-thioxoimidazolidin-2-one derivative 8. Cyclocondensation reaction of 3, 4, 8, and 9 with different arylidene malononitriles afforded fused systems, 5a-e, 6a-e, 10a-e, and 11a-e, respectively. The synthesized compounds were evaluated for their in-vitro antimicrobial activity using the disc diffusion method. In addition, they were evaluated for their in-vitro antiviral activity against avian paramyxovirus type 1 (APMV-1) and laryngotracheitis virus (LTV).
Results and conclusion
In-vitro antimicrobial activity of the newly synthesized compounds included an inhibitory effect toward the growth of Escherichia coli and Pseudomonas aeruginosa (Gram-negative bacteria). Furthermore, of the six selected compounds (2, 3, 4, 7, 8 and 9) tested for their antiviral activity, compounds 2, 3, and 4 at a concentration range of 3–4 µg/ml showed marked viral inhibitory activity for APMV-1 of 5000 tissue culture infected dose fifty (TCID50) and LTV of 500 TCID50 in Vero cell cultures on the basis of their cytopathic effect. Chicken embryo experiments show that compounds 2, 3, and 4 possess high antiviral activity in vitro, with inhibitory concentration fifty (IC50) ranging from 3 to 4 µg/egg against avian APMV-1 and LTV and toxic concentration fifty (CC50) ranging from 200 to 300 µg/egg.