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

Alaa A.M. Abdel-Aziz, Adel S. El-Azab, Amer M. Alanazi, Yousif A. Asiri, Ibrahim A. Al-Suwaidan, Azza R. Maarouf, Rezk R. Ayyad, Taghreed Z. Shawer

Research output: Contribution to journalJournal articlepeer-review

32 Scopus citations

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.

Original languageEnglish
Pages (from-to)796-809
Number of pages14
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume31
Issue number5
DOIs
StatePublished - 2 Sep 2016
Externally publishedYes

Keywords

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

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