OBJECTIVES: To determine antibacterial activity of capuramycin analogues SQ997, SQ922, SQ641 and RKS2244 against several non-tuberculous mycobacteria (NTM). METHODS: In vitro antibiotic activities, i.e. MIC, MBC, rate of killing and synergistic interaction with other antibiotics, were evaluated. RESULTS: SQ641 was the most active compound against all the NTM species studied. The MIC of SQ641 was ≤0.06-4 mg/L for Mycobacterium avium complex (MAC; n = 20), 0.125-2 mg/L for M. avium paratuberculosis (MAP; n = 9), 0.125-2 mg/L for Mycobacterium kansasii (MKN;n = 2), 0.25-1 mg/L for Mycobacterium abscessus (MAB; n = 11), 4 mg/L for Mycobacterium smegmatis (MSMG; n = 1), and 1 and 8 mg/L for Mycobacterium ulcerans (MUL; n = 1), by microdilution and agar dilution methods, respectively. SQ641 was bactericidal against NTM, with an MBC/MIC ratio of 1 to 32, and killed all mycobacteria faster than positive control drugs for each strain. In chequerboard titrations, SQ641 was synergistic with ethambutol against both MAC and MSMG, and was synergistic with streptomycin and rifabutin against MAB. CONCLUSIONS: In vitro, SQ641 was the most potent of the capuramycin analogues against all NTM tested, both laboratory and clinical strains.
OBJECTIVES: To determine antibacterial activity of capuramycin analogues SQ997, SQ922, SQ641 and RKS2244 against several non-tuberculous mycobacteria (NTM). METHODS: In vitro antibiotic activities, i.e. MIC, MBC, rate of killing and synergistic interaction with other antibiotics, were evaluated. RESULTS:SQ641 was the most active compound against all the NTM species studied. The MIC of SQ641 was ≤0.06-4 mg/L for Mycobacterium avium complex (MAC; n = 20), 0.125-2 mg/L for M. avium paratuberculosis (MAP; n = 9), 0.125-2 mg/L for Mycobacterium kansasii (MKN;n = 2), 0.25-1 mg/L for Mycobacterium abscessus (MAB; n = 11), 4 mg/L for Mycobacterium smegmatis (MSMG; n = 1), and 1 and 8 mg/L for Mycobacterium ulcerans (MUL; n = 1), by microdilution and agar dilution methods, respectively. SQ641 was bactericidal against NTM, with an MBC/MIC ratio of 1 to 32, and killed all mycobacteria faster than positive control drugs for each strain. In chequerboard titrations, SQ641 was synergistic with ethambutol against both MAC and MSMG, and was synergistic with streptomycin and rifabutin against MAB. CONCLUSIONS: In vitro, SQ641 was the most potent of the capuramycin analogues against all NTM tested, both laboratory and clinical strains.
Authors: Nicholas D Franz; Juan Manuel Belardinelli; Michael A Kaminski; Louis C Dunn; Vinicius Calado Nogueira de Moura; Michael A Blaha; Dan D Truong; Wei Li; Mary Jackson; E Jeffrey North Journal: Bioorg Med Chem Date: 2017-05-08 Impact factor: 3.641
Authors: Boris V Nikonenko; Albert Kornienko; Konstantin Majorov; Pavel Ivanov; Tatiana Kondratieva; Maria Korotetskaya; Alexander S Apt; Elena Salina; Valeriya Velezheva Journal: Antimicrob Agents Chemother Date: 2016-09-23 Impact factor: 5.191
Authors: Boris Nikonenko; Venkata M Reddy; Elena Bogatcheva; Marina Protopopova; Leo Einck; Carol A Nacy Journal: Antimicrob Agents Chemother Date: 2013-10-21 Impact factor: 5.191
Authors: John H Moore; Edward van Opstal; Glynis L Kolling; Jae Hyun Shin; Elena Bogatcheva; Boris Nikonenko; Leo Einck; Andrew J Phipps; Richard L Guerrant; Marina Protopopova; Cirle Alcantara Warren Journal: J Antimicrob Chemother Date: 2016-01-31 Impact factor: 5.790