indicated desirable apoptotic cell death by photo-generated singlet oxygen (1O2) ... (3a) was ascertained from 1,3-diphenylisobenzofuran (DPBF) experiments.
BODIPY-APPENDED Oxidovanadium(IV) Complexes of Curcumin: Augmented Stability of the ‘Drug’ and Mitochondria-Targeted Visible Light Photocytotoxicity UTSO BHATTACHARYYA (1), BRIJESH KUMAR VERMA (2), ADITYA GARAI (1), ARNAB BHATTACHARYYA (1), ARUN KUMAR (1), SAMYA BANERJEE (1), PATURU KONDAIAH (2) AND AKHIL R. CHAKRAVARTY (1)
(1): Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, India; (2): Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India. ABSTRACT Curcumin (Hcur) is well known for its versatile medicinal properties including anti-cancer efficacy, however, suffers from its poor aqueous solubility and hydrolytic instability in physiological pH of 7.4, which leads to its poor ADME profile. Due to these drawbacks, it has been classified under PAINS (pans-assay interference compounds) and IMPS (invalid metabolic panaceas) [1]. To overcome the limitations, we have introduced a new strategy in which curcumin in its enolic form is observed to augment the stability and aqueous solubility on binding to an oxidovanadium(IV) moiety. Herein we present three ternary oxidovanadium(IV) complexes of curcumin (Hcur), dipicolylamine (dpa) base and its derivatives having pendant boron-dipyrromethene (BODIPY) moiety, namely, [VO(dpa)(cur)]ClO4 (1), [VO(L1)(cur)]ClO4 (2) and [VO(L2)(cur)]ClO4 (3) (and their chloride salts (1a-3a) used in biological studies for their better aqueous solubility). The curcumin complex of dpa (1) was structurally characterized by X-ray crystallography. The emissive BODIPY complex (2a) used for bio-imaging revealed predominant mitochondrial localization. The diiodo-BODIPY complex (3a) displayed excellent PDT activity (IC50 ~2 μM) in human breast cancer MCF-7 cells and cervical cancer HeLa cells in visible light (λ= 400-700 nm) while remaining non-toxic in dark (IC50 >100 μM). Flow-cytometry studies indicated desirable apoptotic cell death by photo-generated singlet oxygen (1O2) from the BODIPY moiety and •
OH from the curcumin (confirmed from DNA photocleavage studies). Significant 1O2 generation ability of the
diiodo-BODIPY complex (3a) was ascertained from 1,3-diphenylisobenzofuran (DPBF) experiments. The results presented offer a new direction in the emerging chemistry of metal-based anticancer agents in PDT.
REFERENCES [1] Nelson, K. M. et al, J. Med. Chem. 2017, 60, 1620-1637. [2] Bhattacharyya, U. and Chakravarty, A. R., et al., Inorg. Chem. 2017, 56, 12457-12468.
