Next Article in Journal
Untangling the Conformational Plasticity of V66M Human proBDNF Polymorphism as a Modifier of Psychiatric Disorder Susceptibility
Previous Article in Journal
Lanthanide (Eu3+/Tb3+)-Loaded γ-Cyclodextrin Nano-Aggregates for Smart Sensing of the Anticancer Drug Irinotecan
Previous Article in Special Issue
A Type Ib Crustin from Deep-Sea Shrimp Possesses Antimicrobial and Immunomodulatory Activity
 
 
Article

Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties

1
Biochemical Research Scientific Association, Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland
2
Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland
3
Bioinformatics Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland
4
Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warsaw, Poland
5
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 02-091 Warsaw, Poland
6
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Ana María Díez-Pascual
Int. J. Mol. Sci. 2022, 23(12), 6600; https://doi.org/10.3390/ijms23126600
Received: 11 May 2022 / Revised: 9 June 2022 / Accepted: 10 June 2022 / Published: 13 June 2022
(This article belongs to the Special Issue New Antibacterial Agents)
Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1–16 µg/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci, within the range of 0.8–1.6 µg/mL and was confirmed as the leading structure with MICs 1 µg/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds (3, 11 and 16) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14–1.11 while the mentioned three ranged 1.9–3.4. Selected Ciprofloxacin derivatives were docked into the crystal structure of topoisomerase II (DNA gyrase) in complex with DNA (PDB ID: 5BTC). In summary, leading structures were established (3, 11, 12 and 16). We have observed poor results in preformed studies for disubstituted derivatives, suggesting that 3-oxo-4-carboxylic acid core is the active DNA-gyrase binding site, and when structural changes were made in this fragment, there was an observed decrease in antibacterial potency. View Full-Text
Keywords: antimicrobial; Ciprofloxacin; antibiotic; thymol; menthol antimicrobial; Ciprofloxacin; antibiotic; thymol; menthol
Show Figures

Figure 1

MDPI and ACS Style

Szostek, T.; Szulczyk, D.; Szymańska-Majchrzak, J.; Koliński, M.; Kmiecik, S.; Otto-Ślusarczyk, D.; Zawodnik, A.; Rajkowska, E.; Chaniewicz, K.; Struga, M.; Roszkowski, P. Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties. Int. J. Mol. Sci. 2022, 23, 6600. https://doi.org/10.3390/ijms23126600

AMA Style

Szostek T, Szulczyk D, Szymańska-Majchrzak J, Koliński M, Kmiecik S, Otto-Ślusarczyk D, Zawodnik A, Rajkowska E, Chaniewicz K, Struga M, Roszkowski P. Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties. International Journal of Molecular Sciences. 2022; 23(12):6600. https://doi.org/10.3390/ijms23126600

Chicago/Turabian Style

Szostek, Tomasz, Daniel Szulczyk, Jolanta Szymańska-Majchrzak, Michał Koliński, Sebastian Kmiecik, Dagmara Otto-Ślusarczyk, Aleksandra Zawodnik, Eliza Rajkowska, Kinga Chaniewicz, Marta Struga, and Piotr Roszkowski. 2022. "Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties" International Journal of Molecular Sciences 23, no. 12: 6600. https://doi.org/10.3390/ijms23126600

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop