Abstract
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•New levofloxacin derivatives were synthesized and structurally elucidated.•The cytotoxic screening against different cancer cell lines were conducted.•The Topoisomerase II beta enzyme inhibition was investigated.•Cell cycle arrest profile, apoptosis, and caspase-3 assay were employed.•Etoposide and levofloxacin were used as reference drugs for comparison.
Newly designed levofloxacin analogues were synthesized to act as topoisomerase II beta inhibitors (Topo2β). Their cytotoxic activity was screened against breast, liver, and leukemia cancer cell lines. The best activity against liver cancer cell line (Hep3B) was exhibited by the target compounds 3c, 3e, 4a, and 6d (IC50 = 2.33, 1.38, 0.60 and 0.43, respectively). (L-SR) leukemia cancer cell line was pronouncedly affected by compounds 3b, 3g and 4a (IC50 = 1.62, 1.41 and 1.61, sequentially). 3c possessed the best activity against breast cancer cell line (MCF-7) with IC50 = 0.66. Compounds 3c, 3e, 3g, 4a and 4c exhibited Topo2β inhibition activities exceeding etoposide and levofloxacin as reference drugs and variant cell lines. In DNA-Flow cytometry cell cycle analysis, compound 3c arrested the cell cycle at G2/M phase like etoposide and levofloxacin, while compounds 3e and 4a exhibit its arrest at S phase. In addition, 3c, 3e and 4a showed a significant elevation in active caspase-3 levels (10.01, 8.98 and 10.71 folds, respectively). The effect of the new compounds on normal cells was also investigated including breast (MCF10a), liver (THLE2), and lymphocytic (PCS-800-011) normal cell lines.