Naphth[1,2-d]imidazoles Bioactive from β-Lapachone: Fluorescent Probes and Cytotoxic Agents to Cancer Cells

Abstract

Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2-d]imidazole compounds were synthesized from β-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 103 to 104), intense fluorescence emissions in the blue region, and large Stokes shifts (20–103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth[1,2-d]imidazoles showed IC50 between 8.71 and 29.92 μM against HL-60 cells. For HCT-116 cells, values for IC50 between 21.12 and 62.11 μM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth[1,2-d]imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.

Cyclocondensation of 2-(α-Diazoacyl)-2H-azirines with Amidines in Diazo Synthesis of Functionalized Naphtho[1,2-d]imidazoles

“…13 The selective cytotoxicity toward cancer cells and the fluorescence of naphtho [1,2-d]imidazoles make possible the application of these compounds in antitumor theranostic systems. 14 It was also found that naphtho [1,2d]imidazole derivatives are promising light-emitting materials for OLEDs. 15−17 Naphtho [1,2-d]imidazoles are usually synthesized by condensation of carbonyl compounds with 1,2-diaminonaphthalene derivatives, 8,11,17−19 often formed in situ.…”

“…Thus, they are nonacidic antiinflammatory agents, antihypertensive agents, , thrombopoietin mimics, potent human histamine H 4 receptor ligands, and HCV NS5A inhibitors . The selective cytotoxicity toward cancer cells and the fluorescence of naphtho­[1,2- d ]­imidazoles make possible the application of these compounds in antitumor theranostic systems . It was also found that naphtho­[1,2- d ]­imidazole derivatives are promising light-emitting materials for OLEDs. − Naphtho­[1,2- d ]­imidazoles are usually synthesized by condensation of carbonyl compounds with 1,2-diaminonaphthalene derivatives, ,,− often formed in situ. , Intramolecular condensation of 1-amido-2-amino/1-amino-2-amido-naphthalenes is also frequently used. ,,,, Another approach involves the cyclization of 1-aminonaphthalene derivatives containing an N-CRN moiety. − In all of the mentioned methods, the assembly of the tricyclic naphtho­[1,2- d ]­imidazole skeleton is completed by the formation of the imidazole ring (imidazole ring-forming strategy) (Scheme , (1a)).…”