title: Curcumin analogues as possible anti-proliferative & anti-inflammatory agents.
abstract: A series of novel curcumin analogues has been designed, synthesized and tested in vitro/in vivo as potential multi-target agents. Their anti-proliferative and anti-inflammatory activities were studied. Compounds 1b and 2b were stronger inhibitors of soybean lipoxygenase (LOX) than curcumin. Analogue 1b was also the most potent aldose reductase (ALR2) inhibitor. Two compounds, (1a and 1f) exhibited in vivo anti-inflammatory activity comparable to that of indomethacin, whereas derivative 1i exhibited even higher activity. The derivatives were also tested for their anti-proliferative activity using three different human cancer cell lines. Compounds 1a, 1b, 1d and 2b exhibited significant growth inhibitory activity as compared to curcumin, against all three cancer cell lines. Lipophilicity was determined as R(M) values using RPTLC and theoretically. The results are discussed in terms of the structural characteristics of the compounds. Docking simulations were performed on LOX and ALR2 inhibitor 1b and curcumin. Compound 1b is well fitted in the active site of ALR2, binding to the ALR2 enzyme in a similar way to curcumin. Allosteric interactions may govern the LOX-inhibitor binding.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: A-M
authors.initials: AM
authors.lastname: Katsori
authors.forename: M
authors.initials: M
authors.lastname: Chatzopoulou
authors.forename: K
authors.initials: K
authors.lastname: Dimas
authors.forename: C
authors.initials: C
authors.lastname: Kontogiorgis
authors.forename: A
authors.initials: A
authors.lastname: Patsilinakos
authors.forename: T
authors.initials: T
authors.lastname: Trangas
authors.forename: D
authors.initials: D
authors.lastname: Hadjipavlou-Litina
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000494:Allosteric Regulation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000737:chemistry*; D062105:Molecular Docking Simulation; D010940:Plant Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D013025:Glycine max / Q000737:chemistry / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D010940:Plant Proteins; C576693:Akr1b1 protein, rat; D000449:Aldehyde Reductase; D008084:Lipoxygenase; D003474:Curcumin; D007213:Indomethacin