2. Academic Validation
  3. N-Acylated Ciprofloxacin Derivatives: Synthesis and In Vitro Biological Evaluation as Antibacterial and Anticancer Agents

N-Acylated Ciprofloxacin Derivatives: Synthesis and In Vitro Biological Evaluation as Antibacterial and Anticancer Agents

  • ACS Omega. 2023 May 18;8(21):18663-18684. doi: 10.1021/acsomega.3c00554.
Marta Struga 1,  Piotr Roszkowski 2,  Anna Bielenica 1,  Dagmara Otto-Ślusarczyk 1,  Karolina Stępień 3,  Joanna Stefańska 3,  Anna Zabost 4,  Ewa Augustynowicz-Kopeć 4,  Michał Koliński 5,  Sebastian Kmiecik 6,  Alina Myslovska 2,  Małgorzata Wrzosek 7
Affiliations

Affiliations

  • 1 Chair and Department of Biochemistry, Medical University of Warsaw, ul. Banacha 1, 02-097 Warsaw, Poland.
  • 2 Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
  • 3 Department of Pharmaceutical Microbiology, Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland.
  • 4 Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
  • 5 Bioinformatics Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland.
  • 6 Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warsaw, Poland.
  • 7 Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland.
PMID: 37273589 DOI: 10.1021/acsomega.3c00554
Abstract

A novel series of N-acylated ciprofloxacin (CP) conjugates 1-21 were synthesized and screened as potential antimicrobial agents. Conjugates 1 and 2 were 1.25-10-fold more potent than CP toward all Staphylococci (minimal inhibitory concentration 0.05-0.4 μg/mL). Most of the chloro- (3-7), bromo- (8-11), and CF3-alkanoyl (14-16) derivatives expressed higher or comparable activity to CP against selected Gram-positive strains. A few CP analogues (5, 10, and 11) were also more effective toward the chosen clinical Gram-negative rods. Conjugates 5, 10, and 11 considerably influenced the phases of the Bacterial growth cycle over 18 h. Additionally, compounds 2, 4-7, 9-12, and 21 exerted stronger tuberculostatic action against three Mycobacterium tuberculosis isolates than the first-line antitubercular drugs. Amides 1, 2, 5, 6, 10, and 11 targeted gyrase and Topoisomerase IV at 2.7-10.0 μg/mL, which suggests a mechanism of Antibacterial action related to CP. These findings were confirmed by molecular docking studies. In addition, compounds 3 and 15 showed high antiproliferative activities against prostate PC3 cells (IC50 2.02-4.8 μM), up to 6.5-2.75 stronger than cisplatin. They almost completely reduced the growth and proliferation rates in these cells, without a cytotoxic action against normal HaCaT cell lines. Furthermore, derivatives 3 and 21 induced Apoptosis/necrosis in PC3 cells, probably by increasing the intracellular ROS amount, as well as they diminished the IL-6 level in tumor cells.

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