Photocytotoxicity and DNA cleavage activity of L-arg and L-lys Schiff base oxovanadium(IV) complexes having phenanthroline bases.
Oxovanadium(IV) complexes [VO(sal-argH)(B)]Cl (1-3) and [VO(sal-lysH)(B)]Cl (4-6), where sal-argH2 and sal-lysH2 are N-salicylidene-L-arginine and N-salicylidene-L-lysine Schiff bases and B is a phenanthroline base, viz. 1,10-phenanthroline (phen in 1 and 4); dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2 and 5) and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 3 and 6), have been prepared, characterized and their DNA photocleavage activity studied. Complex 1, characterized by X-ray crystallography, shows the presence of a vanadyl group in V(IV)O3N3 coordination geometry with a tridentate Schiff base having a pendant guanidinium moiety and bidentate phen ligand. The complexes exhibit a d-d band at 715 nm in 20% DMF-Tris-HCl buffer. The complexes are redox active showing cathodic and anodic responses near -1.0 V and 0.85 V (vs. SCE) for the V(IV)-V(III) and V(V)-V(IV) couples, respectively, in DMF-Tris-HCl buffer. The complexes bind to calf thymus DNA giving Kb values in the range of 3.8 x 10(4) to 1.6 x 10(5) M(-1). Thermal denaturation and viscosity data suggest DNA groove binding nature of the complexes. The complexes do not show any "chemical nuclease" activity in dark in the presence of 3-mercaptopropionic acid or H2O2. The dpq and dppz complexes are efficient photocleavers of plasmid DNA in UV-A (365 nm) and red light (676 nm) via singlet oxygen pathway. The dppz complexes exhibit photocytotoxicity in HeLa cancer cells giving IC50 values of 15.4 microM for 3 and 17.5 microM for 6 in visible light while being non-toxic in dark giving IC50 values of >100 microM.
Sasmal
Pijus K
PK
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India.
Majumdar
Ritankar
R
Dighe
Rajan R
RR
Chakravarty
Akhil R
AR
D000818:Animals; D001120:Arginine / Q000737:chemistry*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000187:drug effects*; D053837:DNA Cleavage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008239:Lysine / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry*; D010777:Photochemistry; D012545:Schiff Bases / Q000737:chemistry; D013237:Stereoisomerism; D014638:Vanadates / Q000737:chemistry*
D009942:Organometallic Compounds; D010618:Phenanthrolines; D012545:Schiff Bases; C075743:oxovanadium IV; D014638:Vanadates; D004247:DNA; C427203:calf thymus DNA; D001120:Arginine; D008239:Lysine