Антимікобактеріальна активність нових похідних арилоксиетокси діалкіламінопропанолу щодо референтних штамів нетуберкульозних мікобактерій

Abstract

Objective. To evaluate the in vitro antimycobacterial activity of novel quaternary ammonium salts,derived from alkyl(aryloxyethoxy)dialkylaminopropanol against reference strains of nontuberculous mycobacteria (NTM).Materials and Methods. A total of 52 synthesized compounds,obtained via phase-transfer catalysis,were stud-ied. The activity was assessed in two stages: initial screening using the agar diffusion method (well method), fol-lowed by minimum inhibitory concentration (MIC) determination through serial dilution. Primary testing was performed on Mycobacterium smegmatis, followed by evaluation on M. terrae, M. avium, and M. B5 using the proportion method on Löwenstein–Jensen medium. Compounds were tested at three concentrations: K-I (MIC for M. smegmatis), K-II (10×MIC), and K-III (100×MIC).Results. Ten compounds with the highest activity against M. smegmatis were identified during the screeningstage. The most active was Kc12 (MIC –0.22±0.02 μg/mL). Other active compounds included: Kc16, Kc13,Kc15, Kp15, Kp20, Kp18, Kc22, Kc14, and Kp16. Among the NTM strains, M. terrae and M. B5 were the mostsensitive. At K-II, compounds Kc12, Kc13, Kc15, Kc16, Kc22, and Kp18 inhibited bacterial growth by more than95 %. Kc15 demonstratedtheefficacy comparable to rifampicin, whileKp18 and Kc12 surpassed streptomycin.M. avium exhibited resistance, with growth suppression below 5 %,observed only at K-III in a few compounds.The least active was Kp20.Conclusions. Ten promising compounds were identified, notably Kc12, Kc15, Kp18, Kc16, and Kc22, whose ac-tivity exceeded that of streptomycin and approached rifampicin in some cases. The findings highlight the poten-tial of these compounds for further preclinical development in the treatment of NTM infections