title: Structure-based design, synthesis, molecular docking, and biological activities of 2-(3-benzoylphenyl) propanoic acid derivatives as dual mechanism drugs.
abstract: OBJECTIVE
  2-(3-benzoyl phenyl)propanohydroxamic acid (2) and 2-{3-[(hydroxyimino)(phenyl)methyl]phenyl}propanoic acid (3) were synthesized from non-steroidal anti-inflammatory drug, ketoprofen as dual-mechanism drugs.
  
  
  METHODS
  Structures of the synthesized compounds were established by IR, (1)H NMR, and mass spectroscopy. Both compounds were screened for their anti-inflammatory activity in rat paw edema model and in vitro antitumor activity against 60 human tumor cell lines. Flexible ligand docking studies were performed with different matrix metalloproteinases and cyclooxygenases to gain an insight into the structural preferences for their inhibition.
  
  
  RESULTS
  Compound (2) proved out to be more potent than ketoprofen in rat paw edema model. Both compounds showed moderate anticancer activity ranging from 1% to 23% inhibition of growth in 38 cell lines of 8 tumor subpanels at 10 μM concentration in a single dose experiment. Hydroxamic acid analogue was found to be more potent than ketoximic analogue in terms of its antitumor activity.
  
  
  CONCLUSIONS
  Analysis of docking results together with experimental findings provide a good explanation for the biological activities associated with synthesized compounds which may be fruitful in designing dual-target-directed drugs that may inhibit cyclooxygenases and MMPs for the treatment of cancer.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Garyounis University, Benghazi, Libya.
authors.forename: Musa A
authors.initials: MA
authors.lastname: Ahmed
authors.forename: Faizul
authors.initials: F
authors.lastname: Azam
authors.forename: Abir M
authors.initials: AM
authors.lastname: Rghigh
authors.forename: Abdul
authors.initials: A
authors.lastname: Gbaj
authors.forename: Abdulmottaleb E
authors.initials: AE
authors.lastname: Zetrini