Journal Article

Evaluation of Anticancer Activity of Nucleoside–Nitric Oxide Photo-Donor Hybrids

Argazzi, Roberto, Perrone, Daniela, Preti, Lorenzo, De Risi, Carmela, Pozza, Elena, Navacchia, Maria Luisa, Casciano, Fabio, Marchesi, Elena, Melloni, Elisabetta

2024

Overview

Herein, we report the synthesis of a new hybrid compound based on a 2′-deoxyuridine nucleoside conjugated with a NO photo-donor moiety (dU-t-NO) via CuAAC click chemistry. Hybrid dU-t-NO, as well as two previously reported 2′-deoxyadenosine based hybrids (dAdo-S-NO and dAdo-t-NO), were evaluated for their cytotoxic and cytostatic activities in selected cancer cell lines. dAdo-S-NO and dAdo-t-NO hybrids displayed higher activity with respect to dU-t-NO. All hybrids showed effective release of NO in the micromolar range. The photochemical behavior of the newly reported hybrid, dU-t-NO, was studied in the RKO colon carcinoma cell line, whereas the dAdo-t-NO hybrid was tested in both colon carcinoma RKO and hepatocarcinoma Hep 3B2.1-7 cell lines to evaluate the potential effect of NO released upon irradiation on cell viability. A customized irradiation apparatus for in vitro experiments was also designed.

• Publisher: MDPI AG
• Subject: Angiogenesis / anticancer activity / Antineoplastic Agents - chemical synthesis / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Cancer therapies / Cell culture / Cell cycle / Cell Line, Tumor / Cell Proliferation - drug effects / Cell Survival - drug effects / Click Chemistry / Colorectal cancer / Deoxyuridine - analogs & derivatives / Deoxyuridine - chemistry / Deoxyuridine - pharmacology / Disease / Humans / hybrid drugs / Liver cancer / Molecular Structure / multitarget anticancer drugs / Nitric oxide / Nitric Oxide - chemistry / Nitric Oxide - metabolism / Nitric Oxide Donors - chemistry / Nitric Oxide Donors - pharmacology / nucleoside analogs / Nucleosides - chemistry / Nucleosides - pharmacology / photo-donor