Antimycobacterial activity of chiral aminoalcohols with camphane scaffold.
A series of aminoalcohols were synthesized by reaction of aminolysis of camphor derived oxiranes with chosen amines. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. Ten of the new structures show much higher activity than the classical anti-TB drug ethambutol. Some of the most active compounds were tested against MDR strain 43, and four of them demonstrated excellent activities with MICs 0.27-0.72 μM. The cytotoxicity of representative exerting antimycobacterial activity compounds was assessed. Quantitative structure-activity relationship (QSAR) model is derived to estimate the contribution of each structural fragment to the activity. The camphane-based aminoalcohols are promising lead compounds for further development of novel antimycobacterial agents.
Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Sciences, Acad. Bonchev 9, Sofia 1113, Bulgaria.
Zhanina
Z
Petkova
Institute of Microbiology, Bulgarian Academy of Sciences, Akad. Bonchev 26, Sofia 1113, Bulgaria.
Violeta
V
Valcheva
Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria.
Georgi
G
Momekov
Faculty of Chemistry and Pharmacy, Sofia University St. Kliment Ohridsky, James Bourchier Blvd. 1, Sofia 1164, Bulgaria.
Petar
P
Petrov
Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Sciences, Acad. Bonchev 9, Sofia 1113, Bulgaria.
Vladimir
V
Dimitrov
Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria.
Irini
I
Doytchinova
Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria. Electronic address: gstavrakov@hotmail.com.
Georgi
G
Stavrakov
Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Sciences, Acad. Bonchev 9, Sofia 1113, Bulgaria. Electronic address: mstoyanova@orgchm.bas.bg.
Malinka
M
Stoyanova
D000605:Amino Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001892:Camphanes / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship
D000605:Amino Alcohols; D000995:Antitubercular Agents; D001892:Camphanes; C067796:camphane
Camphor; Cytotoxicity; MDR TB; Mycobacterium tuberculosis; QSAR