title: Remarkable enhancement in photocytotoxicity and hydrolytic stability of curcumin on binding to an oxovanadium(IV) moiety.
abstract: Oxovanadium(IV) complexes of polypyridyl and curcumin-based ligands, viz. [VO(cur)(L)Cl] (1, 2) and [VO(scur)(L)Cl] (3, 4), where L is 1,10-phenanthroline (phen in 1 and 3), dipyrido[3,2-a:2',3'-c]phenazine (dppz in 2 and 4), Hcur is curcumin and Hscur is diglucosylcurcumin, were synthesized and characterized and their cellular uptake, photocytotoxicity, intracellular localization, DNA binding, and DNA photo-cleavage activity studied. Complex [VO(cur)(phen)Cl] (1) has V(IV)N2O3Cl distorted octahedral geometry as evidenced from its crystal structure. The sugar appended complexes show significantly higher uptake into the cancer cells compared to their normal analogues. The complexes are remarkably photocytotoxic in visible light (400-700 nm) giving an IC50 value of <5 μM in HeLa, HaCaT and MCF-7 cells with no significant dark toxicity. The green emission of the complexes was used for cellular imaging. Predominant cytosolic localization of the complexes 1-4 to a lesser extent into the nucleus was evidenced from confocal imaging. The complexes as strong binders of calf thymus DNA displayed photocleavage of supercoiled pUC19 DNA in red light by generating ˙OH radicals as the ROS. The cell death is via an apoptotic pathway involving the ROS. Binding to the VO(2+) moiety has resulted in stability against any hydrolytic degradation of curcumin along with an enhancement of its photocytotoxicity.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Samya
authors.initials: S
authors.lastname: Banerjee
authors.forename: Ila
authors.initials: I
authors.lastname: Pant
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.forename: Puja
authors.initials: P
authors.lastname: Prasad
authors.forename: Akhtar
authors.initials: A
authors.lastname: Hussain
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D004247:DNA / Q000737:chemistry; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D008027:Light; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014638:Vanadates / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D014638:Vanadates; D004247:DNA; C427203:calf thymus DNA; D003474:Curcumin; D005947:Glucose