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 Name: BIOORGANIC CHEMISTRY
  • 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

Abstract

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.