Synthesis and potential antitumor activity of 7-(4-substituted piperazin-1-yl)-4-oxoquinolines based on ciprofloxacin and norfloxacin scaffolds: in silico studies. (2nd September 2016)

• Record Type: Journal Article
• Authors: Abdel-Aziz, Alaa A.-M.; El-Azab, Adel S.; Alanazi, Amer M.; Asiri, Yousif A.; Al-Suwaidan, Ibrahim A.; Maarouf, Azza R.; Ayyad, Rezk R.; Shawer, Taghreed Z.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 5(2016:Oct.)
• Page Start: 796
• Page End: 809
• Publication Date: 2016-09-02
• Subjects: ADME-T prediction -- antitumor activity -- fluoroquinolones -- in silico study -- synthesis; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2015.1069288
• Languages: English
• ISSNs: 1475-6366

Abstract

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. Compounds1a, 2a, 3b, 6b and7a were found to be the most potent, while2b, 5b, and6a were found to have an average activity. The results of this study demonstrated that compounds1a, 2a, 3b, 6b and7a (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, compounds1a, 2a, 3b, 6b and7a 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.