BODIPY-attached zinc(II) complexes of curcumin drug for visible light assisted photo-sensitization, cellular imaging and targeted PDT

• Published in: European journal of medicinal chemistry 2021-08, Vol.220, p.113438-113438, Article 113438
• Main Authors: Bhattacharyya, Arnab, Jameei, Aida, Karande, Anjali A., Chakravarty, Akhil R.
• Format: Article
• Language: English
• Subjects: Boron-dipyrromethene; Curcumin; Medicinal chemistry; Mitochondrial localization; Photodynamic therapy; Zinc
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2021.113438

Boron-dipyrromethene (BODIPY) based photosensitizers as porphyrinoids and curcumin as natural product possess exciting photophysical features suitable for theranostic applications, namely, imaging and photodynamic therapy (PDT). Limited aqueous solubility and insufficient physiological stability, however, reduce their efficacy significantly. We have designed a novel strategy to deliver these two unusable cytotoxins simultaneously in cancer cells and herein, report the synthesis, characterization and imaging-assisted photocytotoxicity of three zinc(II) complexes containing N3-donor dipicolylamine (dpa) ligands (L1-3) and O,O-donor curcumin (Hcur) viz. [Zn(L1)(cur)]Cl (1), [Zn(L2)(cur)]Cl (2) and [Zn(L3)(cur)]Cl (3), where L2 and L3 have pendant fluorescent BODIPY and non-emissive di-iodo-BODIPY moieties. Metal chelation imparted remarkable biological stability (pH ∼7.4) to the respective ligands and induces significant aqueous solubility. These ternary complexes could act as replacements of the existing metalloporphyrin-based PDT photosensitizers as their visible-light photosensitizing ability is reinforced by the dual presence of blue light absorbing curcumin and green light harvesting BODIPY units. Complex 2 having emissive BODIPY unit L2 and curcumin, showed mitochondria selective localization in HeLa, MCF-7 cancer cells and complex 3, the di-iodinated analogue of complex 2, exhibited type-I/II PDT activity via inducing apoptosis through mitochondrial membrane disruption in cancer cells while being significantly nontoxic in dark and to the healthy cells. Ternary zinc(II) complexes of curcumin drug bearing BODIPY photosensitizers are developed as theranostic metallo-porphyrin/phthalocyanine analogues while imparting significant physiological stability to the respective ligands and exhibiting mitochondria-specific and cancer cell selective apoptotic PDT activity forming singlet oxygen and hydroxyl radicals. [Display omitted] •BODIPY and curcumin are incorporated in zinc complexes for mito-specific PDT.•Zinc(II) binding imparts to physiological stability to curcumin and BODIPY dyes.•Confocal microscopy suggests complex 2 as potent green emissive mitotracker agent.•Complex 3 showed mito-specific apoptotic cytotoxicity via both type-I/II pathways.