Bacterial translation is the process by which messenger RNA is translated into proteins in bacteria. Importantly, the Inhibition of bacterial transcription and translation will inhibit bacterial growth and proliferation.

In this article, we will introduce a bacterial translation inhibitor, NOSO-502.

NOSO-502 exhibits potent antibacterial activity. For example, NOSO-502 inhibits Gram-negative pathogens of the Enterobacteriaceae family, such as E. coli or K. pneumoniae, with MIC values between 0.5 and 4 μg/ml, as well as Stenotrophomonas maltophilia. Besides, NOSO-502 (16 µg/mL and 32 µg/mL; 24 h) causes E.coli ATCC 25922 and K. pneumoniae ATCC 43816 strains to develop resistance to NOSO-502.

NOSO-502 shows well in vitro safety profile. Such as, NOSO-502 decreases the activity of HRPTEpiC cells, but insignificantly increases the expression of heat shock protein 27 (HSP27) and kidney injury molecule 1 (KIM-1). Meanwhile, NOSO-502 (256, 512 μM) shows no effect on HK-2 cell viability at concentrations up to 512 μM (0% inhibition from 16 to 256 μM and 9.4% inhibition at 512 μM). Moreover, the NOSO-502 does not significantly inhibit hERG currents at concentrations up to 512 μM (2.6% inhibition at 256 μM and 1.9% inhibition at 512 μM). Additionally, NOSO-502 is resistant to biotransformation by hepatocytes and microsomes.

NOSO-502 shows good pharmacokinetics in vivo. Particularly, NOSO-502 (30 mg/kg; i.v. for mice; 15 mg/kg, i.v. for rat) shows a moderate clearance (1.13 liters/h/kg) and a half-life of 25 min in mice; shows a longer half-life (90 min) in the rat. Besides, NOSO-502 (1.3-40 mg/kg; s.c.; single dose) shows antibacterial activity in NMRI mice infected <i>E. coli</i> EN122. Meanwhile, NOSO-502 (4-24 mg/kg; s.c.; single dose) shows a protective effect in C3H/HeN mice infected E. coli UTI89. Moreover, NOSO-502 (2-80 mg/kg; s.c.; single dose) shows a protective effect in CD-1/ICR mice infected K. pneumoniae NCTC 13442.

All in all, NOSO-502 is a potent bacterial translation inhibitor against enterobacteriaceae and shows anti-infective and protective effects in vivo.

Reference：

[1] Racine E, et al. Antimicrob Agents Chemother. 2018 Aug 27;62(9):e01016-18.