ZTW-41, a Potent Indolizinoquinoline-5,12-Dione Derivative Against Drug-Resistant Staphylococci and Enterococci Bacteria.

ZTW-41, an indolizinoquinoline-5,12-dione derivative, was investigated for antibacterial activity against Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). In our study, the MIC90s (minimum inhibitory concentrations) of ZTW-41 against MRSA (MRSA, n = 200), methicillin-sensitive S. aureus (MSSA, n = 100), Enterococcus faecalis (E. faecalis, n = 32), and Enterococcus faecium (E. faecium n = 32) were 0.25, 0.25, 0.125, and 8 µg/mL, respectively, whereas the MBC90s (minimum bactericidal concentrations) were 2, 1, 1, and >32 µg/mL, respectively. ZTW-41 maintained its potency at different pH levels (range 5-9) and in starting inoculum size up to 107 CFU/mL. The presence of human serum (25-75%) increased ZTW-41 MICs by two- to eightfold. Time-kill curves showed that ZTW-41 had bactericidal activity against MRSA, MSSA, and E. faecalis strains within 8 hours, and rebound growth occurred after 8 hours except at higher multiples of the MIC (4 × and 8 × ). In the acute toxicity study, no mortality or signs of toxicity was noted in mice after 14 days of observation at doses <50 mg/kg. ZTW-41 exhibited good selectivity indices (SIs) (SI = IC50/MIC90) ranging from 1.12 to 71.76 against clinical isolates, demonstrating excellent therapeutic selectivity in MRSA, MSSA, and E. faecalis strains. Moreover, the in vivo efficacy (effective dose [ED]50 = 6.59 mg/kg) of ZTW-41 was found comparable with vancomycin. Collectively, our favorable results supported ZTW-41 as a promising investigational candidate for treating drug-resistant bacteria infection.

Ethyl 4-[(4-chloro-phen-oxy)meth-yl]-2-(4-nitro-phen-yl)-1,3-thia-zole-5-carboxyl-ate.

The title compound, C(19)H(15)ClN(2)O(5)S, contains two mol-ecules (A and B) in the asymmetric unit. In mol-ecule A, the dihedral angles between the thia-zole ring and the pendant chloro-benzene and nitro-benzene rings are 72.14 (15) and 3.03 (15)°, respectively. The corresponding angles for mol-ecule B are 45.56 (16) and 1.51 (14)°, respectively. In the crystal, both mol-ecules form inversion dimers linked by pairs of weak C-H⋯O inter-actions.