Citreoindole

The emergence of antibiotic resistance to commercially- available antibiotics is becoming a major health crisis worldwide. Non-antibiotic strategies are needed to combat biofilm-associated infectious diseases caused by multidrug resistant (MDR) bacterial pathogens. In this study, MBR1 was isolated from a membrane bioreactor used in wastewater treatment plants, and the resistance profile was explored. 5-Nitroindole (5 N)-capped CuO/ZnO bimetal nanoparticles (5 NNP) were synthesized using a one pot method to improve the antibacterial and antibiofilm activities of 5 N against Gram-negative (Escherichia coli ATCC700376 and Pseudomonas aeruginosa PA01) and positive (Staphylococcus aureus ATCC6538) human pathogens. 5 NNP containing 1 mM of 5 N exhibited strong antibacterial and antibiofilm properties to most MDR bacteria. In addition, the photocatalytic activity of CuO/ZnO reduced bacterial cell growth by 1.8 log CFU/mL maximum when exposed to visible light. Scanning electron microscopy showed that 5 NNP reduced the cell density and biofilm attachment of MBR1 by >90% under static conditions. In addition to the antimicrobial and antibiofilm activities, 5 NNP inhibited the persister cell formation of MDR bacterial strains P. aeruginosa, MBR1, E. coli and S. aureus. Therefore, it is speculated that 5 NNP potentially inhibits biofilm and persister cells; hence, 5 NNP could be an alternative agent to combat MDR infectious diseases using a non-antibiotic therapeutic approach.

Few methods are known for the synthesis of nitroindole derivatives. A simple and practical Cs2CO3-promoted method for the synthesis of 6-nitroindole derivatives from enaminones and nitroaromatic compounds has been developed. Two new C-C and C-N bonds were formed in a highly regioselective manner under transition metal-free conditions.

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5'- and 3'-ends) in a 2 : 1 stoichiometry.