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. 2021 Apr 1;22(4):1075-1086.
doi: 10.31557/APJCP.2021.22.4.1075.

A Novel Class of Functionalized Synthetic Fluoroquinolones with Dual Antiproliferative - Antimicrobial Capacities

Abdelrahman Al-Nuaimi  1 , Yusuf Al-Hiari  1 , Violet Kasabri  1 , Randa Haddadin  1 , Noor Mamdooh  1 , Sundus Alalawi  1 , Sara Khaleel  2
Affiliations

A Novel Class of Functionalized Synthetic Fluoroquinolones with Dual Antiproliferative - Antimicrobial Capacities

Abdelrahman Al-Nuaimi et al. Asian Pac J Cancer Prev. .

Abstract

As vosaroxin as a fluoroquinolone (FQ) had anticancer effectiveness; this study aimed to screen new lipophilic FQs for their dual antimicrobial-antiproliferative activities. Using sulforhodamine B assay; 36 lipophilic FQs have been screened for antimicrobial propensities against S. aureus, E. coli, and C. albicans vs. the respective references ciprofloxacin and fluconazole. They were also explored against a battery of cancer cell lines. Normal periodontal ligament fibroblasts (PDL) were tested for safety examination in comparison to the cisplatin. Reduced FQ compound 4g (R-2, 4-DMeOACA) highly scored nanomolar potency with MIC value of 0.004 µM against gram-positive bacteria. The highest activity of the 36 lipophilic FQs was noted on Leukaemia K562, cervical HELA and pancreatic PANC-1 cancer cell lines with respective IC50 value of 0.005 µM for compound R-4-BuACA (4e), 0.40 µM with CHxCA (7a) and 0.11 µM for R-4-HxACA (4f). Tested FQs exhibited cytotoxicity in A549 lung cancer, MCF-7 and T47D breast cancer cell lines. The reduced 4e and 4f compounds have shown nanomolar inhibition against K562 (as of 4e), PANC-1 and MCF-7 (as of 4f) with IC50 values of 0.005, 0.11 and 0.30 µM, respectively. Succinctly FQs' dual gram-positive antibacterial-antineoplastic capacities expand on of drug design scaffolds in lead generation.<br />.

Keywords: Cisplatin and cancer; Fluoroquinolones; Quinolones; Sulphorodhamine B; Triazoloquinolones.

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Conflict of interest statement

Authors declare NONE.

Figures

Figure 1
Figure 1
New FQs by Our Group and Their IC50 against Colon Cancer Cells (Arabiyat et al. 2016a,b; 2017; Alabsi et al. 2018; Jumah 2018; AlShahrabi et al., 2020)
Figure 2
Figure 2
SAR Requirements for of Functionalities in Relevance of Growth Inhibition Activity of FQs Class
Figure 3
Figure 3
Order of Growth Inhibition Activity Based on Optimized Structural Classification of Tested Compounds in Strong Group (Table 3)
See this image and copyright information in PMC

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