Photocytotoxic cancer cell-targeting platinum(ii) complexes of glucose-appended curcumin and biotinylated 1,10-phenanthroline

Upadhyay, A and Gautam, S and Ramu, V and Kondaiah, P and Chakravarty, AR (2019) Photocytotoxic cancer cell-targeting platinum(ii) complexes of glucose-appended curcumin and biotinylated 1,10-phenanthroline. In: Dalton Transactions, 48 (47). pp. 17556-17565.

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Abstract

Mixed-ligand platinum(ii) complexes, [Pt(phen)(pacac)](NO3) (1), [Pt(phen)(cur)](NO3) (2), [Pt(bt-phen)(cur)](NO3) (3) and [Pt(phen)(scur)](NO3) (4), where phen is 1,10-phenanthroline, bt-phen is 5-biotin-1,10-phenanthroline, pacac is 1,3-diphenyl-1,3-propanedioate anion, Hcur is curcumin and Hscur is diglucosylcurcumin, were prepared, characterized and their anticancer activity studied. Complexes 2-4 showed absorption bands within 410-430 nm (ϵ, 2.1 × 104 to 2.8 × 104 M-1 cm-1) in 10% DMSO-DPBS (Dulbecco's phosphate-buffered saline) and emission bands near 530 nm (λex = 410-430 nm) with a fluorescence quantum yield (ΦF) value of ∼0.02. The curcumin complexes showed stability over a study period of 48 h. The photocytotoxicity was studied using human cervical HeLa, human liver HepG2, human breast cancer MDA-MB 231 and human lung adenocarcinoma A549 cancer cells along with human immortalized lung epithelial HPL1D as normal cells. Complexes 2-4 showed apoptotic photo-induced cell death in light of wavelength 400-700 nm (IC50, half maximal inhibitory concentration: 6-28 μM) by reactive oxygen species (ROS), while remaining inactive in the dark (IC50: 43-95 μM). The selectivity of the complexes 3 and 4 was enhanced significantly towards the cancer cells than towards the normal cells, thus making them targeted photochemotherapeutic agents. The ROS formation and mode of cell death were studied from 2′,7′-dichlorofluorescein diacetate (DCFDA) and annexin-V/FITC (fluorescein isothiocyanate)-PI assays, respectively. Preferential nuclear and mitochondrial localization was evidenced from inductively coupled plasma mass spectrometry (ICP-MS) studies.

Item Type:	Journal Article
Publication:	Dalton Transactions
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs to Royal Society of Chemistry.
Keywords:	Biological organs; Cell death; Diseases; Inductively coupled plasma mass spectrometry, Anticancer activities; Cancer cell targeting; Fluorescein isothiocyanate; Fluorescence quantum yield; Inductively coupled plasma mass spectrometries (ICPMS); Inhibitory concentration; Phosphate-buffered salines; Reactive oxygen species, Platinum compounds, 1,10-phenanthroline; antineoplastic agent; curcumin; glucose; phenanthroline derivative; photosensitizing agent; platinum complex; reactive oxygen metabolite, apoptosis; biotinylation; cell proliferation; cell survival; chemical structure; chemistry; density functional theory; dose response; drug delivery system; drug effect; drug screening; human; metabolism; molecular model; structure activity relation; synthesis; tumor cell line; X ray crystallography, Antineoplastic Agents; Apoptosis; Biotinylation; Cell Line, Tumor; Cell Proliferation; Cell Survival; Crystallography, X-Ray; Curcumin; Density Functional Theory; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Screening Assays, Antitumor; Glucose; Humans; Models, Molecular; Molecular Structure; Organoplatinum Compounds; Phenanthrolines; Photosensitizing Agents; Reactive Oxygen Species; Structure-Activity Relationship
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	05 Dec 2022 06:48
Last Modified:	05 Dec 2022 06:48
URI:	https://eprints.iisc.ac.in/id/eprint/78230

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