Synthesis of a 3,4-Disubstituted 1,8-Naphthalimide-Based DNA Intercalator for Direct Imaging of Legionella pneumophila

Abstract

The development of organic molecules to target nucleic acid is an active area of research at the interface of chemistry and biochemistry, which involves DNA binding, nuclear imaging, and antitumor studies. These molecules bind with DNA through covalent interactions, electrostatic interactions, or intercalation. However, they are less permeable to membrane, and they have a significant cytotoxicity, which limits their application under in vivo conditions. In the present work, various mono- and disubstituted 1,8-naphthalimides-based derivatives ( S-12 , S-13 , S-15 , and S-21 ) have been synthesized and characterized through various spectroscopic techniques. Among these, 3-amino-4-bromo-1,8-naphthalimide ( S-15 ) was found to have an attractive water solubility and act as a nuclear imaging agent. The spectroscopic absorption and emission data showed that S-15 has a strong affinity for salmon sperm DNA with a binding constant of 6.61 × 10 4 M –1 , and the ratiometric fluorescence intensity ( I 489 / I 552 ) of S-15 has a linear relationship in the 0–50 μM range of DNA concentrations. It intercalates with DNA through the hydrophobic planar naphthalimide core as confirmed through cyclic voltammetry, circular dichroism, 1 H NMR titration, and thermal denaturation studies. Positively charged amine groups also participate in H-bonding with the bases and backbone of DNA. The S-15 intercalator showed a large Stokes shift and photostability, which made it attractive for direct imaging of Legionella pneumophila , without the need for a prior membrane permeabilization.

Spectroscopic and electrochemical study of interactions between DNA and different salts of 1,4-dihydropyridine AV-153

“…We did not observe a decrease in the peak current, which is considered the main consequence of drug-DNA complex formation (Sirajuddin, Ali & Badshah, 2013). We also observed a significant increase in the peak current during the formation of the complex between DNA and terbium(III)-deferasirox (Shaghaghi et al, 2014) or 3,4-disubstituted 1,8-naphthalimide (Sharma et al, 2019). Thus, the increase in peak current, which is slight in the case of AV-153 salts, can be interpreted as a consequence of DNA and drug interaction.…”

Ruthenium(II)‐Catalyzed C−H Alkenylation of 1,8‐Naphthalimide with Cyclic Imide as a Weakly Coordinating Directing Group

“…1 H NMR (400 MHz, CDCl 3 ) δ (ppm): 8.90 (d, J = 16.0 Hz, 1H), 8.70 (d, J = 8.0 Hz, 1H), 8.25 (dd, J = 8. 3,4.8 Hz,2H),2H),2H),1H), 7.32-7.29 (m, 2H), 6.39 (d, J = 16.0 Hz,1H), 4.25 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ (ppm): 166.…”

“…166.42, 164.45, 163.98, 144.98, 141.52, 135.50, 134.41, 134.21, 132.41, 132.16, 129.54, 129.11, 128.87, 128.73,128.07, 127.48, 124.03, 122.96, 119.72, 67.44, 38.83, 30.49, 28.98, 23.84, 23.06, 14.16, 11.09. HRMS (ESI TOF MS): m/z calculated for C 29 H 29 NO 4 [M + 1] + 456.2130, found 456.2140. bis(2-Ethylhexyl) 3,isoquinoline-4,9-diyl)(2E,2'E)-diacrylate (3 t'). Yellow solid, yield (52 mg, 22%), m. p. 268-270 °C, R f = 0.23 (70 : 30 CHCl 3 :C 6 H 14 ).…”

“…1 H NMR (400 MHz, CDCl 3 ) δ (ppm): 8.91 (dd, J = 16.0, 5.3 Hz,1H),2H),1H),6.92 (s,1H),6.35 (dd,J = 16.0,3.5 Hz,1H),6H),3.85 (d,J = 3.8 Hz,2H),2H),2H), 0.95 (t, J = 7.3 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ (ppm): 166.54, 163.47, 162.05, 149.64, 144.51, 141.97, 130.97, 130.60, 130.09, 129.64, 128.96, 126.98, 124.24, 124.01, 119.92, 52.30, 41.00, 30.08, 20.46, 13.90 3,isoquinoline-4,9-diyl)(2E,2'E)-diacrylate (3 aa'). Yellow solid, yield (58 mg, 37%), m. p. 264-246 °C, R f = 0.33 (80 : 20 CHCl 3 :C 6 H 14 ).…”

Synthesis and Anti-tumor Effects of Naphthalimide Derivatives Targeted in Cell Nucleus

“…因此, 基于萘酰亚胺类衍生物良好的荧光特征和抗 肿瘤作用, 我们设计合成了系列手性氨基醇修饰的萘酰 亚胺衍生物 NI1～NI8 (Scheme 1), 手性氨基醇分子包 括(R)-2-氨基-1-丙醇、(S)-2-氨基-1-丙醇、(R)-1-氨基-2-丙醇、(S)-1-氨基-2-丙醇、(R)-2-氨基丁醇、(S)-2-氨基丁 醇、(R)-3-氨基-1,2-丙二醇和(S)-3-氨基-1,2-丙二醇等, 通过四甲基偶氮唑蓝(MTT)法研究了 NI1～NI8 的抗肿 [21] [22] 与 Ct-DNA 有 效络合. 接着通过非线性拟合方法 [23] [21] 1.6 萘酰亚胺衍生物的血液毒性研究 根据文献报道, 萘酰亚胺类衍生物虽具有好的抗肿 瘤作用, 但其高的血液毒性限制了其临床应用 [26] [21] .…”