Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity
Quinone methide precursors <b>1a</b>–<b>e</b>, with different alkyl linkers between the naphthol and the naphthalimide chromophore, were synthesized. Their photophysical properties and photochemical reactivity were investigated and connected with biological activity. Upon exc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/11/3355 |
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| author | Matija Sambol Patricia Benčić Antonija Erben Marija Matković Branka Mihaljević Ivo Piantanida Marijeta Kralj Nikola Basarić |
| author_facet | Matija Sambol Patricia Benčić Antonija Erben Marija Matković Branka Mihaljević Ivo Piantanida Marijeta Kralj Nikola Basarić |
| author_sort | Matija Sambol |
| collection | DOAJ |
| description | Quinone methide precursors <b>1a</b>–<b>e</b>, with different alkyl linkers between the naphthol and the naphthalimide chromophore, were synthesized. Their photophysical properties and photochemical reactivity were investigated and connected with biological activity. Upon excitation of the naphthol, Förster resonance energy transfer (FRET) to the naphthalimide takes place and the quantum yields of fluorescence are low (Φ<sub>F</sub> ≈ 10<sup>−2</sup>). Due to FRET, photodehydration of naphthols to QMs takes place inefficiently (Φ<sub>R</sub> ≈ 10<sup>−5</sup>). However, the formation of QMs can also be initiated upon excitation of naphthalimide, the lower energy chromophore, in a process that involves photoinduced electron transfer (PET) from the naphthol to the naphthalimide. Fluorescence titrations revealed that <b>1a</b> and <b>1e</b> form complexes with ct-DNA with moderate association constants <i>K</i><sub>a</sub> ≈ 10<sup>5</sup>–10<sup>6</sup> M<sup>−1</sup>, as well as with bovine serum albumin (BSA) <i>K</i><sub>a</sub> ≈ 10<sup>5</sup> M<sup>−1</sup> (1:1 complex). The irradiation of the complex <b>1e@BSA</b> resulted in the alkylation of the protein, probably via QM. The antiproliferative activity of <b>1a</b>–<b>e</b> against two human cancer cell lines (H460 and MCF 7) was investigated with the cells kept in the dark or irradiated at 350 nm, whereupon cytotoxicity increased, particularly for <b>1e</b> (>100 times). Although the enhancement of this activity upon UV irradiation has no imminent therapeutic application, the results presented have importance in the rational design of new generations of anticancer phototherapeutics that absorb visible light. |
| first_indexed | 2024-03-10T10:46:56Z |
| format | Article |
| id | doaj.art-89fce37d67524be5bab8ddccb3c1447f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:46:56Z |
| publishDate | 2021-06-01 |
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| spelling | doaj.art-89fce37d67524be5bab8ddccb3c1447f2023-11-21T22:33:32ZengMDPI AGMolecules1420-30492021-06-012611335510.3390/molecules26113355Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological ActivityMatija Sambol0Patricia Benčić1Antonija Erben2Marija Matković3Branka Mihaljević4Ivo Piantanida5Marijeta Kralj6Nikola Basarić7Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaDivision of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaDepartment of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaDepartment of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaDivision of Material Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaDepartment of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaDivision of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaDepartment of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaQuinone methide precursors <b>1a</b>–<b>e</b>, with different alkyl linkers between the naphthol and the naphthalimide chromophore, were synthesized. Their photophysical properties and photochemical reactivity were investigated and connected with biological activity. Upon excitation of the naphthol, Förster resonance energy transfer (FRET) to the naphthalimide takes place and the quantum yields of fluorescence are low (Φ<sub>F</sub> ≈ 10<sup>−2</sup>). Due to FRET, photodehydration of naphthols to QMs takes place inefficiently (Φ<sub>R</sub> ≈ 10<sup>−5</sup>). However, the formation of QMs can also be initiated upon excitation of naphthalimide, the lower energy chromophore, in a process that involves photoinduced electron transfer (PET) from the naphthol to the naphthalimide. Fluorescence titrations revealed that <b>1a</b> and <b>1e</b> form complexes with ct-DNA with moderate association constants <i>K</i><sub>a</sub> ≈ 10<sup>5</sup>–10<sup>6</sup> M<sup>−1</sup>, as well as with bovine serum albumin (BSA) <i>K</i><sub>a</sub> ≈ 10<sup>5</sup> M<sup>−1</sup> (1:1 complex). The irradiation of the complex <b>1e@BSA</b> resulted in the alkylation of the protein, probably via QM. The antiproliferative activity of <b>1a</b>–<b>e</b> against two human cancer cell lines (H460 and MCF 7) was investigated with the cells kept in the dark or irradiated at 350 nm, whereupon cytotoxicity increased, particularly for <b>1e</b> (>100 times). Although the enhancement of this activity upon UV irradiation has no imminent therapeutic application, the results presented have importance in the rational design of new generations of anticancer phototherapeutics that absorb visible light.https://www.mdpi.com/1420-3049/26/11/3355naphtholsnaphthalimidesFRETPETquinone methidesantiproliferative activity |
| spellingShingle | Matija Sambol Patricia Benčić Antonija Erben Marija Matković Branka Mihaljević Ivo Piantanida Marijeta Kralj Nikola Basarić Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity Molecules naphthols naphthalimides FRET PET quinone methides antiproliferative activity |
| title | Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity |
| title_full | Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity |
| title_fullStr | Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity |
| title_full_unstemmed | Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity |
| title_short | Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity |
| title_sort | photochemical reactivity of naphthol naphthalimide conjugates and their biological activity |
| topic | naphthols naphthalimides FRET PET quinone methides antiproliferative activity |
| url | https://www.mdpi.com/1420-3049/26/11/3355 |
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