Novel synthetic bis-indolic derivatives with antistaphylococcal activity, including against MRSA and VISA strains

Abstract

We have synthesized and characterized novel bis-indole derivatives as promising candidates for the development of new antistaphylococcal treatments, with preserved activity against MDR S. aureus strains.

Efflux pump inhibitors of clinically relevant multidrug resistant bacteria

“…Cytotoxicity assays against three different human cell lines were performed and 5 was considered as noncytotoxic at a concentration of 1 µM . A series of further bis ‐indole derivatives was prepared with the best compounds displaying NorA inhibitory activity equipotent to 5 . However, there have been no data for in vivo efficacy or progress of these potent NorA inhibitors toward clinical evaluation.…”

“…Bis ‐indole derivatives constitute another example in which an iodine atom was considered as a potentially labile functionality which could manifest toxicity after its release. Newly synthesized potent analogs thus possessed a chlorine or bromine atom instead (compare 17 ; Figure and 5 ; Figure ) . In addition, the position of the methoxy group on the 2‐phenylquinoline nucleus was recognized as being unimportant in terms of toxicity, but piperidine in the side chain was favored over a N , N ‐diethyl group, thus creating safer compounds ( 4 ; Figure ) .…”

“…185 A series of further bis-indole derivatives was prepared with the best compounds displaying NorA inhibitory activity equipotent to 5. 186 However, there have been no data for in vivo efficacy or progress of these potent NorA inhibitors toward clinical evaluation.…”

“…Newly synthesized potent analogs thus possessed a chlorine or bromine atom instead (compare 17; Figure 5 and 5; Figure 1). [184][185][186] In addition, the position of the methoxy group on the 2-phenylquinoline nucleus was recognized as being unimportant in terms of toxicity, but piperidine in the side chain was favored over a N,N-diethyl group, thus creating safer compounds (4; Figure 1). 199 Many natural products have been investigated so far in the attempt to obtain less toxic inhibitors, but the main drawback of natural compounds is their structural complexity, often associated with difficulties in establishing a good SAR, thus hindering their further development.…”

Antimicrobial Activity of Galangin and Its Effects on Murein Hydrolases of Vancomycin-Intermediate Staphylococcus aureus (VISA) Strain Mu50

“…Compared with MRSA strains, Mu50 and Mu50-like strains have a thickened cell wall, release more cell wall material into the culture medium, and have different rates of autolysis [9,10,11]. Antibiotic treatment for infections caused by VISA or VRSA strains is challenging [12,13], and few effective and curative methods have been developed to combat these strains.…”