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

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...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 23; no. 12; p. 6600
Main Authors:	Szostek, Tomasz, Szulczyk, Daniel, Szymańska-Majchrzak, Jolanta, Koliński, Michał, Kmiecik, Sebastian, Otto-Ślusarczyk, Dagmara, Zawodnik, Aleksandra, Rajkowska, Eliza, Chaniewicz, Kinga, Struga, Marta, Roszkowski, Piotr
Format:	Journal Article
Language:	English
Published:	Basel MDPI AG 13-06-2022 MDPI
Subjects:	Antibacterial activity antibiotic Antibiotics antimicrobial Antimicrobial activity Antimicrobial agents Bacteria Binding sites Biofilms Carboxylic acids Ciprofloxacin Costs Crystal structure Cytotoxicity Deoxyribonucleic acid Design DNA DNA structure DNA topoisomerase DNA topoisomerase (ATP-hydrolysing) Doxorubicin Drug resistance Economic impact GDP Gonorrhea Gram-positive bacteria Gross Domestic Product Infections Menthol Microorganisms Oils & fats Staphylococcus aureus Strains (organisms) Thymol United States > US
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms23126600