| Autor: |
Banaspati A; Department of Chemistry, Gauhati University Guwahati 781014 Assam India tridibgoswami05@gmail.com., Ramu V; Department of Inorganic and Physical Chemistry, Indian Institute of Science Bangalore 560012 India kausarraza91@gmail.com., Raza MK; Department of Inorganic and Physical Chemistry, Indian Institute of Science Bangalore 560012 India kausarraza91@gmail.com., Goswami TK; Department of Chemistry, Gauhati University Guwahati 781014 Assam India tridibgoswami05@gmail.com. |
| Abstrakt: |
Three copper(ii) complexes viz. [Cu(cur)(L)(ClO 4 )] (1-3), where Hcur is curcumin and L is 1,10-phenanthroline (phen, 1), dipyrido[3,2- d :2',3'- f ]quinoxaline (dpq, 2), or dipyrido[3,2- a :2',3'- c ]phenazine (dppz, 3) were synthesized, fully characterized by various physicochemical methods and evaluated for their light-assisted chemotherapeutic potential. The complexes [Cu(acac)(L)(ClO 4 )] (4-6), where Hacac is acetylacetone and L is phen (in 4), dpq (in 5) and dppz (in 6), were synthesized and used as controls. The solid state structures of complexes 4 and 5 were determined by single crystal X-ray diffraction. The curcumin complexes (1-3) were redox inactive at the copper centre, whereas the acetylacetonato complexes (4-6) displayed a Cu(ii)/Cu(i) couple at ∼0.1 V vs. Ag/AgCl reference electrode in DMF. Complexes 1-3 showed an intense curcumin-based band at ∼440 nm in DMF-Tris-HCl buffer (pH = 7.2) (1 : 9 v/v) which masks the copper based d-d band. The complexes bind to human serum albumin (HSA) with moderate efficacy. They also displayed significant binding affinity for calf-thymus (CT) DNA. The lipophilic curcumin complexes show remarkable visible light induced cytotoxicity (IC 50 = ∼4 μM) with high phototoxic indices (PI) with low dark toxicity in human cervical carcinoma (HeLa) and human lung carcinoma (A549) cells. The corresponding acetylacetonato controls (4-6) did not show significant cytotoxicity in the dark or light. DCFDA and annexin V-FITC/PI assays using flow cytometry confirm the induction of significant apoptosis in cancer cells via generation of cytotoxic reactive oxygen species upon photoactivation. Confocal microscopic images using complex 3 demonstrate localization of the complexes predominantly in the endoplasmic reticulum of HeLa cells.
Competing Interests: There is no conflict of interest to declare.
(This journal is © The Royal Society of Chemistry.) |
