Synthesis and potential antitumor activity of 7-(4-substituted piperazin-1-yl)-4-oxoquinolines based on ciprofloxacin and norfloxacin scaffolds: in silico studies

Abstract

The potential antitumor activities of a series of 7-(4-substituted piperazin-1-yl)fluoroquinolone derivatives (1–14a,b) using ciprofloxacin and norfloxacin as scaffolds are described. These compounds exhibit potent and broad spectrum antitumor activities using 60 human cell lines in addition to the inherent antibacterial activity. Compounds 1a, 2a, 3b, 6b and 7a were found to be the most potent, while 2b, 5b, and 6a were found to have an average activity. The results of this study demonstrated that compounds 1a, 2a, 3b, 6b and 7a (mean GI₅₀; 2.63–3.09 µM) are nearly 7-fold more potent compared with the positive control 5-fluorouracil (mean GI₅₀; 22.60 µM). More interestingly, compounds 1a, 2a, 3b, 6b and 7a have an almost antitumor activity similar to gefitinib (mean GI₅₀; 3.24 µM) and are nearly 2-fold more potent compared to erlotinib (mean GI₅₀; 7.29 µM). In silico study and ADME-Tox prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.

• ADME-T prediction
• antitumor activity
• fluoroquinolones
• in silico study
• synthesis

Acknowledgements

The authors would like to express their gratitude and thanks to the National Cancer Institute (NCI), Bethesda Maryland, USA, http://dtp.cancer.gov/ for doing the antitumor testing of the new compounds.

Declaration of interest

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding the work through the research group project No. RG-1435-046.

Supplementary material available online

Supplementary Figures S1 and S2