Brominated plastoquinone analogs: Synthesis, structural characterization, and biological evaluation

A series of brominated PQ analogs (BrPQ1-13) was synthesized by employing two different routes: 1) dibromination followed by oxidation and amination of dimethyl hydroquinone, respectively, 2) oxidation of dimethyl hydroquinone followed by amination and bromination, respectively. In addition to the single-crystal X-ray structural characterization of two analogs (BrPQ2 and BrPQ3), the structures of all analogs were determined based on spectral (FTIR, H-1 NMR, C-13 NMR, and HRMS) data. We evaluated the analogs for in vitro antibacterial and antifungal activity against ATCC (R) strains (panel of seven bacterial strains with three Gram-positive and four Gram-negative bacteria and three fungi) using the broth microdilution method. The structure-activity relationship of brominated PQ analogs indicated that the electron-withdrawing group (EWG) on the phenyl ring (-CF3, trifluoromethyl group) has a positive effect on antibacterial activity. These in vitro data show that brominated analogs, especially for BrPQ 1, BrPQ2, and BrPQ3, have the potential to be developed as new antibacterial agents against S. aureus and/or S. epidermidis with low MIC values. (C) 2020 Elsevier B.V. All rights reserved.