Novel 5-Nitrofuran-Tagged Imidazo-Fused Azines and Azoles Amenable by the Groebke–Blackburn–Bienaymé Multicomponent Reaction: Activity Profile against ESKAPE Pathogens and Mycobacteria
Alexander Sapegin,
Elizaveta Rogacheva,
Lyudmila Kraeva,
Maxim Gureev,
Marine Dogonadze,
Tatiana Vinogradova,
Petr Yablonsky,
Saeed Balalaie,
Sergey V. Baykov,
Mikhail Krasavin
Affiliations
Alexander Sapegin
Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia
Elizaveta Rogacheva
Pasteur Institute of Epidemiology and Microbiology, 14 Mira Street, Saint Petersburg 197101, Russia
Lyudmila Kraeva
Pasteur Institute of Epidemiology and Microbiology, 14 Mira Street, Saint Petersburg 197101, Russia
Maxim Gureev
Laboratory of Chemoinformatics and Bioinformatics, Sechenov First Moscow State Medical University, Moscow 119435, Russia
Marine Dogonadze
Saint Petersburg Research Institute of Phthisiopulmonology, 2-4 Ligovsky Prospekt, Saint Petersburg 191036, Russia
Tatiana Vinogradova
Saint Petersburg Research Institute of Phthisiopulmonology, 2-4 Ligovsky Prospekt, Saint Petersburg 191036, Russia
Petr Yablonsky
Saint Petersburg Research Institute of Phthisiopulmonology, 2-4 Ligovsky Prospekt, Saint Petersburg 191036, Russia
Saeed Balalaie
Peptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran 19697, Iran
Sergey V. Baykov
Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia
Mikhail Krasavin
Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia
A chemically diverse set of 13 5-nitrofuran-tagged heterocyclic compounds has been prepared via the Groebke–Blackburn–Bienaymé multicomponent reaction. The testing of these compounds against the so-called ESKAPE panel of pathogens identified an apparent lead compound—N-cyclohexyl-2-(5-nitrofuran-2-yl)imidazo[1,2-a]pyridine-3-amine (4a)—which showed an excellent profile against Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis (MIC 0.25, 0.06, 0.25 and 0.25 µg/mL, respectively). Its antibacterial profile and practically convenient synthesis warrant further pre-clinical development. Certain structure-activity relationships were established in the course of this study which were rationalized by the flexible docking experiments in silico. The assessment of antitubercular potential of the compounds synthesized against drug sensitive H37v strain of Mycobacterium tuberculosis revealed little potential of the imidazo-fused products of the Groebke–Blackburn–Bienaymé multicomponent reaction as chemotherapeutic agents against this pathogen.
