Exploration of brominated Plastoquinone analogs: Discovery and structure-activity relationships of small antimicrobial lead molecules

YILDIZ M., BAYRAK N., YILDIRIM H., Mataraci-Kara E., Shilkar D., Jayaprakash V., ...More

BIOORGANIC CHEMISTRY, vol.116, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 116
  • Publication Date: 2021
  • Doi Number: 10.1016/j.bioorg.2021.105316
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database, Index Chemicus (IC)
  • Keywords: Aminobenzoquinone, Bromine, Plastoquinones, Antimicrobial activity, Antibiofilm activity, Bactericidal activity, Molecular docking, Predictive ADMET, DERIVATIVES, ANTICANCER, AGENTS, 1,4-NAPHTHOQUINONES, NAPHTHOQUINONES, PYRANOPYRAZOLES, INHIBITORS, QUINONES
  • Istanbul University Affiliated: Yes


In the fight with the antimicrobial resistance, our continuous effort to find quinone analogs with higher inhibitory activity has previously led us to the promising Plastoquinone analogs. The 1,4-quinone moiety substituted with alkoxy substituent(s) plays an important role in the field of antimicrobial and anticancer drug discovery and development. Thus, an extensive series of 1,4-quinones, substituted in different positions with a variety of alkoxy substituents, has been designed, synthesized, and evaluated for their antimicrobial activity. Here, we describe the synthesis of brominated Plastoquinone analogs (BrPQ1-15) based on the dimethyl-1,4-quinone scaffold by employing two different paths. We also present here the in vitro antimicrobial activity of these analogs (BrPQ115) against a panel of pathogenic organisms. These studies resulted in several new selective antibacterial inhibitors and gave valuable insights into the structure-activity relationships. Among all the analogs studied, two analogs BrPQ1 with a methoxy substituent and BrPQ14 with a cyclic dioxy stand out as the most promising antibacterial molecules against Staphylococcus aureus and Staphylococcus epidermidis. Afterwards, two analogs were selected for a further investigation for biofilm evaluation. Finally, molecular docking studies for BrPQ1 and BrPQ14 with probable target S. aureus PNPase (5XEX) and predictive ADMET studies were also carried out.