Curcumin “Drug” Stabilized in Oxidovanadium(IV)-BODIPY Conjugates for Mitochondria-Targeted Photocytotoxicity

Abstract

Ternary oxidovanadium(IV) complexes of curcumin (Hcur), dipicolylamine (dpa) base, and its derivatives having pendant noniodinated and di-iodinated boron-dipyrromethene (BODIPY) moiety (L and L, respectively), namely, [VO(dpa)(cur)]ClO (1), [VO(L)(cur)]ClO (2), and [VO(L)(cur)]ClO (3) and their chloride salts (1a-3a) were prepared, characterized, and studied for anticancer activity. The chloride salts were used for biological studies due to their aqueous solubility. Complex 1 was structurally characterized by single-crystal X-ray crystallography. The complex has a VO moiety bound to dpa ligand showing N,N,N-coordination in a facial mode, and curcumin is bound in its mono-anionic enolic form. The V-O(cur) distances are 1.950(18) and 1.977(16) Å, while the V-N bond lengths are 2.090(2), 2.130(2), and 2.290(2) Å. The bond trans to V═O is long due to trans effect. The complexes are stable in a solution phase over a long period of time of 48 h without showing any apparent degradation of the curcumin ligand. The diiodo-BODIPY ligand (L) or Hcur alone showed limited solution stability in dark. The emissive BODIPY (L) containing complex 2a showed preferential mitochondrial localization in MCF-7 cells in cellular imaging experiments. The cytotoxicity of the complexes was studied by MTT assay. The BODIPY complex 3a showed excellent photodynamic therapy effect in visible light (400-700 nm) giving IC values of 2-6 μM in HeLa and MCF-7 cancer cells, while being less toxic in dark (∼100 μM). The cell death was apoptotic in nature involving reactive oxygen species (ROS). Mechanistic data from pUC19 DNA photocleavage studies revealed photogenerated ROS as primarily O from the BODIPY moiety and ·OH radicals from the curcumin ligand.

ROS dependent antitumour activity of photo-activated iron(III) complexes of amino acids

“…[11][12][13][14][15] Bio-essential and kinetically labile first-row transition metal complexes absorbing light in PDT window (600-700 nm) are, however, preferable for photo-chemotherapeutic applications, Considering greater tissue penetration, longer wavelength absorbing and stable photo-active complexes of biocompatible metal ions like vanadium, cobalt, copper or iron have been explored in PDT window to various cancer cell lines. [16][17][18][19][20][21] The present work originated from our interest to develop iron(III)-based complexes for photo-activated chemotherapy by exploring the photo-labile nature of the iron(III)-carboxylates or iron(III)-phenolates on photo-activation at LMCT band generating cytotoxic hydroxyl radical. 17,22,23 Recently, we explored the photochemistry of the oxo-bridged diiron(III) complexes for photochemotherapeutic applications to various cancer cell lines.…”

Evaluation of curcumin-mediated photodynamic therapy on the reverse of multidrug resistance in tumor cells

“…4,5 As reported, the IC 50 of HeLa cells treated with photoactive CUR was 0.1 times that of nonphotoactive CUR and the photodynamic antitumor effect of CUR on human epithelial carcinoma A431 cells was signicantly enhanced by CUR-mediated photodynamic therapy (PDT) compared with control without light irradiation. 6,7 PDT is a treatment that uses photosensitizing agents, along with light and oxygen to kill cancer cells by the generation of ROS. 8 Photosensitizers as the core component of PDT only work aer they have been activated or "turned on" by certain kinds of light.…”

Photochemotherapy of Infrared Active BODIPY-Appended Iron(III) Catecholates for in Vivo Tumor Growth Inhibition

“…These requirements have necessitated design and development of new generation of drugs including those of transition metal-based. 5−8 Iron is a natural choice as a substitute of platinum for its biocompatibility and based on the utility of bleomycins (BLMs) as iron-based anticancer agents. 9−12 BLMs are glycopeptide antitumor antibiotics that cleave DNA in an oxidative manner.…”