The cis-Diammineplatinum(II) Complex of Curcumin: A Dual Action DNA Crosslinking and Photochemotherapeutic Agent

• Published in: Angewandte Chemie International Edition Vol. 54; no. 47; pp. 13989 - 13993
• Main Authors: Mitra, Koushambi, Gautam, Srishti, Kondaiah, Paturu, Chakravarty, Akhil R.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16.11.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antitumor agents; Cattle; Cell Death - drug effects; cell imaging; Cell Proliferation - drug effects; Cross-Linking Reagents - chemistry; curcumin; Curcumin - chemistry; Curcumin - pharmacology; Deoxyribonucleic acid; DNA; DNA - chemistry; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Light; Microscopy, Fluorescence; Molecular Structure; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology; Photochemotherapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; platinum; Prodrugs - chemistry; Prodrugs - pharmacology; Prodrugs - radiation effects; Quantum Theory; Structure-Activity Relationship; cell imaging; platinum; DNA; antitumor agents; curcumin
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201507281

[Pt(cur)(NH3)2](NO3) (1), a curcumin‐bound cis‐diammineplatinum(II) complex, nicknamed Platicur, as a novel photoactivated chemotherapeutic agent releases photoactive curcumin and an active platinum(II) species upon irradiation with visible light. The hydrolytic instability of free curcumin reduces upon binding to platinum(II). Interactions of 1 with 5′‐GMP and ct‐DNA indicated formation of platinum‐bound DNA adducts upon exposure to visible light (λ=400–700 nm). It showed apoptotic photocytotoxicity in cancer cells (IC50≈15 μM), thus forming ⋅OH, while remaining passive in the darkness (IC50>200 μM). A comet assay and platinum estimation suggest Pt–DNA crosslink formation. The fluorescence microscopic images showed cytosolic localization of curcumin, thus implying possibility of dual action as a chemo‐ and phototherapeutic agent. Double duty: The title complex shows dual cellular activity by photorelease of curcumin as a photodynamic therapy (PDT) agent and formation of a cisplatin analogue as a transcription inhibitor (IC50≈15 μM). Cellular platinum estimation suggests a DNA crosslink formation and fluorescence images reveal cytosolic localization.