title: Novel chloroquinoline derivatives incorporating biologically active benzenesulfonamide moiety: synthesis, cytotoxic activity and molecular docking.
abstract: BACKGROUND
  Quinoline derivatives have diverse biological activities including anticancer activity. On the other hand, many sulfonamide derivatives exhibited good cytotoxic activity. Hybrids of both moieties may present novel anticancer agents.
  
  
  RESULTS
  Chloroquinoline incorporating a biologically active benzene-sulfonamide moieties 5-21 and diarylsulfone derivatives 22 and 23 were prepared using (E)-1-(4-((E)-7-chloro-1-methylquinolin-4(1H)-ylideneamino)phenyl)-3-(dimethyl-amino)prop-2-en-1-one 4 as strategic starting material. The structure of the newly synthesized compounds were confirmed by elemental analyses and spectral data. Compound 4 was confirmed by X-ray crystallographic analysis. The prepared compounds were evaluated for their anticancer activity against Lung, HeLa, Colorectal and breast cancer cell lines. Compounds 2, 4, 7, 11, 14 and 17 showed better or comparable activity to 2', 7'-dichlorofluorescein (DCF) as reference drug. Molecular docking of the active compounds on the active site of PI3K enzyme was performed in order to explore the binding mode of the newly synthesized compounds.
  
  
  CONCLUSIONS
  Compounds 2, 4, 7, 11, 14 and 17 are novel quinoline derivatives that may represent good candidates for further evaluations as anticancer agents. The mechanism of action of these compounds could be through inhibition of PI3K enzyme.Graphical abstractCompound 17 on the active site of PI3K.
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451 Saudi Arabia ; Department of Drug Radiation Research, National Center for Radiation Research and Technology, Nasr City, Cairo, 113701 Egypt.
authors.forename: Mostafa M
authors.initials: MM
authors.lastname: Ghorab
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451 Saudi Arabia.
authors.forename: Mansour S
authors.initials: MS
authors.lastname: Alsaid
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451 Saudi Arabia.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Al-Dosari
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Yassin M
authors.initials: YM
authors.lastname: Nissan
authors.affiliation: Medicinal, Aromatic and Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451 Saudi Arabia.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Al-Mishari
keywords: Anticancer activities; Benzenesulfonamides; Chloroquinolines