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

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.

• Authors: Aarti Upadhyay , Srishti Gautam , Vanitha Ramu , Paturu Kondaiah , Akhil R Chakravarty
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 48 Issue 47 Pg. 17556-17565 (Dec 03 2019) ISSN: 1477-9234 [Electronic] England
• PMID: 31748772 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Phenanthrolines
• Photosensitizing Agents
• Reactive Oxygen Species
• Curcumin
• Glucose
• 1,10-phenanthroline

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Biotinylation
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Crystallography, X-Ray
• Curcumin (chemistry)
• Density Functional Theory
• Dose-Response Relationship, Drug
• Drug Delivery Systems
• Drug Screening Assays, Antitumor
• Glucose (chemistry)
• Humans
• Models, Molecular
• Molecular Structure
• Organoplatinum Compounds (chemical synthesis, chemistry, pharmacology)
• Phenanthrolines (chemistry)
• Photosensitizing Agents (chemical synthesis, chemistry, pharmacology)
• Reactive Oxygen Species (metabolism)
• Structure-Activity Relationship