Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study.
A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% cytotoxic concentration (CC50), 50% inhibiting concentration (IC50) and selectivity index (SI) were calculated for each compound. It was found that some of synthesized benzimidazole derivatives (7 of 22, 32%) possess strong virus-inhibiting activity against pandemic influenza virus (IC50's in low micromolar range) with quite moderate cytotoxicity (CC50in the range of thousands micromoles). Due to their high selectivity (highest SI's=50-83) these compounds are of significant interest for further in vivo experiments as well as for further structural optimization and drug development.
Influenza Research Institute, St. Petersburg, Russia. Electronic address: zarubaev@influenza.spb.ru.
Vladimir V
VV
Zarubaev
Southern Federal University, Rostov-on-Don, Russia.
Anatolii S
AS
Morkovnik
Southern Federal University, Rostov-on-Don, Russia.
Liudmila N
LN
Divaeva
Influenza Research Institute, St. Petersburg, Russia.
Liubov' A
LA
Karpinskaya
Southern Federal University, Rostov-on-Don, Russia.
Gennadii S
GS
Borodkin
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
C000621696:2-iminobenzimidazoline; D000998:Antiviral Agents; D001562:Benzimidazoles
2-Acylaminobenzimidazoles; 2-Iminobenzimidazolines; 2-Thioureidobenzimidazoles; Antiviral activity; Cytotoxicity; Influenza virus