Escaping ESKAPE resistance: and studies of multifunctional carbamimidoyl-tethered indoles against antibiotic-resistant bacteria.

Combining the hybridization and repurposing strategies, six compounds from our in-house library and having a designed hybrid structure of MBX-1162, pentamidine and MMV688271 were repurposed as potential antibacterial agents. Among, compounds and elicited potential sub-µg ml activity against the high-priority antibiotic-resistant Gram-positive members of ESKAPE bacteria as well as antibiotic-susceptible Gram-positive bacteria. Furthermore, they showed potential low µg ml activity against the explored critical-priority antibiotic-resistant Gram-negative members of ESKAPE bacteria. In time-kill assay, compound has effective 0.5 and 0.25 µg ml antibacterial lethal concentrations against MRSA in exponential growth phase. investigations predicted compounds and as inhibitors of the open conformation of undecaprenyl diphosphate synthase involved in bacterial isoprenoid synthesis. In addition, compounds and were predicted as inhibitors of NADPH-free but not NADPH-bound form of ketol-acid reductoisomerase and may also serve as potential B-DNA minor groove binders with possible differences in the molecular sequence recognition. Overall, compounds and are presented as multifunctional potential antibacterial agents for further development against high- and critical-priority Gram-positive and Gram-negative antibiotic-resistant ESKAPE bacterial pathogens as well as antibiotic-susceptible Gram-positive bacterial pathogens.