Copper(ii) curcumin complexes for endoplasmic reticulum targeted photocytotoxicity† † Electronic supplementary information (ESI) available: Selected crystallographic data for complexes 4 and 5 (Tables S1 and S2) (CCDC 2192685 and 2192686 for complexes 4 and 5 respectively), DNA and protein binding constants (Table S3), synthetic schemes (S1 and S2) and figures showing mass spectra of ligand and the complexes (S1–S6), IR spectra (S7–S12), electronic spectra (S13), cyclic voltammograms (S14), UV-visible spectra for stability measurements (S15 and S16), unit cell packing diagrams (S17 and S18), DNA binding plots (S19), protein binding plots (S20), fluorescence intensity decay profile (S21), cytotoxicity data (S22–S25), flow cytometry data (S26–S28). CCDC 2192685 and 2192686. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d2ra04813b

ABSTRACT: Three copper(ii) complexes viz. [Cu(cur)(L)(ClO4)] (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)(ClO4)] (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 (IC50 = ∼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. Cu(ii) curcumin complexes show significant photo-enhanced cytotoxicity in HeLa and A549 cancer cells in visible light via an apoptosis mechanism through generation of ROS with low dark toxicity.

SUBMITTER: Banaspati A 

PROVIDER: S-EPMC9606729 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature