title: Copper(II) complexes of substituted salicylaldehyde dibenzyl semicarbazones: synthesis, cytotoxicity and interaction with quadruplex DNA.
abstract: A series of substituted salicylaldehyde dibenzyl semicarbazones [RC6H3(OH)CH=N-NHCON(CH2Ph)2] and their copper(II) complexes were synthesized and characterized. The chloridocopper(II) complexes of the 4-OH and 5-OH substituted ligands (complexes 9 and 7) show modest affinity and good selectivity (over duplex DNA) for the quadruplex formed from the human telomeric (HTelo) DNA sequence. Substitution of the chlorido ligands of these two complexes with pyridine yielded derivatives (7-py and 9-py) with increased affinity for HTelo. These derivatives also show good selectivity for HTelo over calf-thymus DNA (170- and 211-fold, respectively). The X-ray crystal structures of 9 and 9-py were determined. Molecular docking studies based on these structures show that the complexes stack on the 5'-end of the HTelo quadruplex, with the hydroxyl group forming a hydrogen bond with a guanine residue. Complexes 7, 9, 7-py and 9-py display significant cytotoxicity against MOLT-4 human leukaemia cells. Interestingly, they have low to negligible cytotoxicity against the non-cancerous IMR-90 human fibroblasts.
authors.affiliation: Natural Sciences & Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616. yawkai.yan@nie.edu.sg.
authors.forename: Siti
authors.initials: S
authors.lastname: Munira Haidad Ali
authors.forename: Yaw-Kai
authors.initials: YK
authors.lastname: Yan
authors.forename: Peter P F
authors.initials: PP
authors.lastname: Lee
authors.forename: Kenny Zhi Xiang
authors.initials: KZ
authors.lastname: Khong
authors.forename: Mahasin
authors.initials: M
authors.lastname: Alam Sk
authors.forename: Kok Hwa
authors.initials: KH
authors.lastname: Lim
authors.forename: Beata
authors.initials: B
authors.lastname: Klejevskaja
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilar
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D001632:Bibenzyls / Q000737:chemistry; D001665:Binding Sites; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D012664:Semicarbazones / Q000737:chemistry*; D016615:Telomere / Q000378:metabolism
chemical_list: D000447:Aldehydes; D001632:Bibenzyls; D056831:Coordination Complexes; D012664:Semicarbazones; C013243:salicylaldehyde; D003300:Copper; D004247:DNA; C427203:calf thymus DNA