Investigating the Antibacterial Activity of Biphenylthiazoles against Methicillin- and Vancomycin-Resistant <i>Staphylococcus aureus</i> (MRSA and VRSA)

Phenylthiazoles were reported previously as a new scaffold with antibacterial activity against an array of multidrug-resistant staphylococci. However, their promising antibacterial activity was hampered in large part by their short half-life due to excessive hepatic clearance. Close inspection of the structure–activity-relationships (SARs) of the phenylthiazoles revealed two important structural features necessary for antibacterial activity (a nitrogenous and a lipophilic component). Incorporating the nitrogenous part within a pyrimidine ring resulted in analogues with a prolonged half-life, while the biphenyl moiety revealed the most potent analogue <b>1b</b>. In this study, advantageous moieties have been combined to generate a new hybrid scaffold of 5-pyrimidinyl­biphenyl­thiazole with the objective of enhancing both anti-MRSA activity and drug-like properties. Among the 37 tested biphenylthiazoles, piperazinyl-containing derivatives <b>10</b>, <b>30</b>, and <b>36</b> were the most potent analogues with MIC values as low as 0.39 μg/mL. Additionally, <b>36</b> exhibited significant improvement in stability to hepatic metabolism

New indole derivatives as multi-target anti-Alzheimer's agents; synthesis, biological evaluation and molecular dynamics - supporting material final.docx

   S1: 3D interaction diagram of donepezil, & compound 11 with AChE (4EY7). S2: 2D interaction diagram of compounds; donepezil, 5, 7 & 11 with BChE (6QAE). S3: 2D interaction diagram between NADPH-Oxidase (2CDU) & donepezil, compounds; 5, 7 & 11. S4: 3D interaction diagram of donepezil & active Compound 5 with NADPH-Oxidase (2CDU). S5: H1-NMR of compound 3 S6: C13-NMR of compound 3 S7: Mass spectrum of compound 3 S8: H1-NMR of compound 4 S9: C13-NMR of compound 4 S10: Mass spectrum of compound 4 S11: H1-NMR of compound 5 S12: C13-NMR of compound 5 S13: Mass spectrum of compound 5 S14: H1-NMR of compound 6 S15: C13-NMR of compound 6 S16: Mass spectrum of compound 6 S17: H1-NMR of compound 7 S18: C13-NMR of compound 7 S19: Mass spectrum of compound 7 S20: H1-NMR of compound 8 S21: C13-NMR of compound 8 S22: Mass spectrum of compound 8 S23: H1-NMR of compound 9 S24: C13-NMR of compound 9 S25: Mass spectrum of compound 9 S26: H1-NMR of compound 10 S27: C13-NMR of compound 10 S28: H1-NMR of compound 11 S29: C13-NMR of compound 11 S30: Mass spectrum of compound 11 S31: H1-NMR of compound 12 S32: C13-NMR of compound 12 S33: Mass spectrum of compound 12 S34: H1-NMR of compound 13 S35: C13-NMR of compound 13 S36: Mass spectrum of compound 13 S37: H1-NMR of compound 14 S38: C13-NMR of compound 14 S39: Mass spectrum of compound 14 S40: H1-NMR of compound 15 S41: C13-NMR of compound 15 S42: Results of in vitro Biological Evaluation </p