title: 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.
authors.affiliation: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .|b Department of Medicinal Chemistry, Faculty of Pharmacy , University of Mansoura , Mansoura , Egypt .
authors.forename: Alaa A-M
authors.initials: AA
authors.lastname: Abdel-Aziz
authors.affiliation: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .|c Department of Organic Chemistry, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt .
authors.forename: Adel S
authors.initials: AS
authors.lastname: El-Azab
authors.affiliation: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors.forename: Amer M
authors.initials: AM
authors.lastname: Alanazi
authors.affiliation: d Department of Clinical Pharmacy , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors.forename: Yousif A
authors.initials: YA
authors.lastname: Asiri
authors.affiliation: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Al-Suwaidan
authors.affiliation: b Department of Medicinal Chemistry, Faculty of Pharmacy , University of Mansoura , Mansoura , Egypt .|e Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Delta University for Science & Technology , Gamasa City , Egypt , and.
authors.forename: Azza R
authors.initials: AR
authors.lastname: Maarouf
authors.affiliation: f Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt.
authors.forename: Rezk R
authors.initials: RR
authors.lastname: Ayyad
authors.affiliation: f Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt.
authors.forename: Taghreed Z
authors.initials: TZ
authors.lastname: Shawer
mesh_terms: D042462:4-Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation; D002939:Ciprofloxacin / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D015394:Molecular Structure; D009643:Norfloxacin / Q000737:chemistry*; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D042462:4-Quinolones; D000970:Antineoplastic Agents; D010879:Piperazines; D000077489:Piperazine; D002939:Ciprofloxacin; D009643:Norfloxacin
keywords: ADME-T prediction; antitumor activity; fluoroquinolones; in silico study; synthesis