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1.
Chem Commun (Camb) ; 60(65): 8565-8568, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39044711

RESUMEN

A series of naphthalimide dyes (TRNATR, MOTNAMOT, MPNAMP, TYNATY, PNAP and IZNAIZ) were designed and synthesized by altering the side chains of the naphthalimide. Without the need for ER-targeting groups, the first five dyes were found to specifically target the ER, likely due to their well-suited lipophilic properties. Furthermore, TRNATR and TYNATY were proven effective for studying ER stress, showing promise in tracking ER autophagy in living cells triggered by tunicamycin and nutritional starvation.


Asunto(s)
Retículo Endoplásmico , Colorantes Fluorescentes , Naftalimidas , Naftalimidas/química , Naftalimidas/síntesis química , Retículo Endoplásmico/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Imagen Óptica , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estructura Molecular , Células HeLa , Autofagia/efectos de los fármacos
2.
Bioorg Chem ; 150: 107596, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38941699

RESUMEN

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.


Asunto(s)
Antineoplásicos , Bencenosulfonamidas , Anhidrasa Carbónica IX , Inhibidores de Anhidrasa Carbónica , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Ferroptosis , Naftalimidas , Sulfonamidas , Neoplasias de la Mama Triple Negativas , Humanos , Anhidrasa Carbónica IX/antagonistas & inhibidores , Anhidrasa Carbónica IX/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Ferroptosis/efectos de los fármacos , Sulfonamidas/farmacología , Sulfonamidas/química , Sulfonamidas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Ratones , Femenino , Naftalimidas/química , Naftalimidas/farmacología , Naftalimidas/síntesis química , Descubrimiento de Drogas , Apoptosis/efectos de los fármacos , Simulación del Acoplamiento Molecular , Piperazinas/farmacología , Piperazinas/química , Piperazinas/síntesis química , Línea Celular Tumoral , Antígenos de Neoplasias
3.
Molecules ; 29(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38930839

RESUMEN

A tumor-targeting fluorescent probe has attracted increasing interest in fluorescent imaging for the noninvasive detection of cancers in recent years. Sulfonamide-containing naphthalimide derivatives (SN-2NI, SD-NI) were synthesized by the incorporation of N-butyl-4-ethyldiamino-1,8-naphthalene imide (NI) into sulfonamide (SN) and sulfadiazine (SD) as the tumor-targeting groups, respectively. These derivatives were further characterized by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), and a fluorescence assay. In vitro properties, including cell cytotoxicity and the cell uptake of tumor cells, were also evaluated. Sulfonamide-containing naphthalimide derivatives possessed low cell cytotoxicity to B16F10 melanoma cells. Moreover, SN-2NI and SD-NI can be taken up highly by B16F10 cells and then achieve good green fluorescent images in B16F10 cells. Therefore, sulfonamide-containing naphthalimide derivatives can be considered to be the potential probes used to target fluorescent imaging in tumors.


Asunto(s)
Colorantes Fluorescentes , Naftalimidas , Sulfonamidas , Naftalimidas/química , Naftalimidas/síntesis química , Sulfonamidas/química , Sulfonamidas/síntesis química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Ratones , Línea Celular Tumoral , Humanos , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier , Supervivencia Celular/efectos de los fármacos
4.
Molecules ; 29(10)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38792143

RESUMEN

Strigolactones (SLs) have potential to be used in sustainable agriculture to mitigate various stresses that plants have to deal with. The natural SLs, as well as the synthetic analogs, are difficult to obtain in sufficient amounts for practical applications. At the same time, fluorescent SLs would be useful for the mechanistic understanding of their effects based on bio-imaging or spectroscopic techniques. In this study, new fluorescent SL mimics containing a substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive furan-2-one moiety were prepared. The structural, spectroscopic, and biological activity of the new SL mimics on phytopathogens were investigated and compared with previously synthetized fluorescent SL mimics. The chemical group at the C-6 position of the naphthalimide ring influences the fluorescence parameters. All SL mimics showed effects similar to GR24 on phytopathogens, indicating their suitability for practical applications. The pattern of the biological activity depended on the fungal species, SL mimic and concentration, and hyphal order. This dependence is probably related to the specificity of each fungal receptor-SL mimic interaction, which will have to be analyzed in-depth. Based on the biological properties and spectroscopic particularities, one SL mimic could be a good candidate for microscopic and spectroscopic investigations.


Asunto(s)
Lactonas , Naftalimidas , Naftalimidas/química , Naftalimidas/síntesis química , Naftalimidas/farmacología , Lactonas/química , Lactonas/farmacología , Lactonas/síntesis química , Estructura Molecular , Ascomicetos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Rhizoctonia/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos
5.
Bioorg Med Chem Lett ; 107: 129776, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38692523

RESUMEN

Human cytochrome P450 1B1 enzyme (hCYP1B1), a member of hCYP1 subfamily, plays a crucial role in multiple diseases by participating in many metabolic pathways. Although a suite of potent hCYP1B1 inhibitors have been previously reported, most of them also act as aryl hydrocarbon receptor (AhR) agonists that can up-regulate the expression of hCYP1B1 and then counteract their inhibitory potential in living systems. This study aimed to develop novel efficacious hCYP1B1 inhibitors that worked well in living cells but without AhR agonist effects. For these purposes, a series of 1,8-naphthalimide derivatives were designed and synthesized, and their structure-activity relationships (SAR) as hCYP1B1 inhibitors were analyzed. Following three rounds SAR studies, several potent hCYP1B1 inhibitors were discovered, among which compound 3n was selected for further investigations owing to its extremely potent anti-hCYP1B1 activity (IC50 = 0.040 nM) and its blocking AhR transcription activity in living cells. Inhibition kinetic analyses showed that 3n potently inhibited hCYP1B1 via a mix inhibition manner, showing a Ki value of 21.71 pM. Docking simulations suggested that introducing a pyrimidine moiety to the hit compound (1d) facilitated 3n to form two strong interactions with hCYP1B1/heme, viz., the C-Br⋯π halogen bond and the N-Fe coordination bond. Further investigations demonstrated that 3n (5 µM) could significantly reverse the paclitaxel (PTX) resistance in H460/PTX cells, evidenced by the dramatically reduced IC50 values, from 632.6 nM (PTX alone) to 100.8 nM (PTX plus 3n). Collectively, this study devised a highly potent hCYP1B1 inhibitor (3n) without AhR agonist effect, which offered a promising drug candidate for overcoming hCYP1B1-associated drug resistance.


Asunto(s)
Citocromo P-450 CYP1B1 , Diseño de Fármacos , Naftalimidas , Humanos , Relación Estructura-Actividad , Naftalimidas/farmacología , Naftalimidas/química , Naftalimidas/síntesis química , Citocromo P-450 CYP1B1/antagonistas & inhibidores , Citocromo P-450 CYP1B1/metabolismo , Estructura Molecular , Relación Dosis-Respuesta a Droga
6.
Eur J Med Chem ; 271: 116416, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38657480

RESUMEN

Targeting polo-box domain (PBD) small molecule for polo-like kinase 1 (PLK1) inhibition is a viable alternative to target kinase domain (KD), which could avoid pan-selectivity and dose-limiting toxicity of ATP-competitive inhibitors. However, their efficacy in these settings is still low and inaccessible to clinical requirement. Herein, we utilized a structure-based high-throughput virtual screen to find novel chemical scaffold capable of inhibiting PLK1 via targeting PBD and identified an initial hit molecule compound 1a. Based on the lead compound 1a, a structural optimization approach was carried out and several series of derivatives with naphthalimide structural motif were synthesized. Compound 4Bb was identified as a new potent PLK1 inhibitor with a KD value of 0.29 µM. 4Bb could target PLK1 PBD to inhibit PLK1 activity and subsequently suppress the interaction of PLK1 with protein regulator of cytokinesis 1 (PRC1), finally leading to mitotic catastrophe in drug-resistant lung cancer cells. Furthermore, 4Bb could undergo nucleophilic substitution with the thiol group of glutathione (GSH) to disturb the redox homeostasis through exhausting GSH. By regulating cell cycle machinery and increasing cellular oxidative stress, 4Bb exhibited potent cytotoxicity to multiple cancer cells and drug-resistant cancer cells. Subcutaneous and oral administration of 4Bb could effectively inhibit the growth of drug-resistant tumors in vivo, doubling the survival time of tumor bearing mice without side effects in normal tissues. Thus, our study offers an orally-available, structurally-novel PLK1 inhibitor for drug-resistant lung cancer therapy.


Asunto(s)
Antineoplásicos , Proteínas de Ciclo Celular , Proliferación Celular , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Pulmonares , Naftalimidas , Quinasa Tipo Polo 1 , Inhibidores de Proteínas Quinasas , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas , Naftalimidas/química , Naftalimidas/farmacología , Naftalimidas/síntesis química , Humanos , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Relación Estructura-Actividad , Ratones , Estructura Molecular , Resistencia a Antineoplásicos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Neoplasias Experimentales/metabolismo
7.
ChemMedChem ; 19(15): e202400114, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38676621

RESUMEN

In the present study, naphthalimide-pyrazole-benzothiazole based fluorescent analogs were synthesized by substituting different primary and secondary amines on the naphthalimide nucleus and were evaluated for their sensitivity and selectivity towards serum albumin. Among various synthesized analogues compound 25 showed the most significant change with serum albumin and was further studied for selective detection and mode of interaction with serum albumin. Here, we compared the binding interaction of fluorescent probe 25 for variation/detection of two 76 % structurally resembling proteins HSA and BSA, by spectroscopic experiments. The compound shows more selectivity for HSA and BSA with a higher binding constant and evident visible change in the emission spectra of two serum albumins among different bioanalytes. The mode of interaction of 25 with human serum albumin and bovine serum albumin was investigated by FT-IR, circular dichroism, and DLS techniques to find out the change in the microenvironment and variation in the structure of serum albumin proteins. Higher binding affinity and specific selectivity of 25 with a limit of detection of 0.69 µM and 1.4 µM towards HSA and BSA compared to other bioanalytes make it a significant fluorescent probe for quantitatively detecting serum albumins at the very early stage of many fatal diseases.


Asunto(s)
Colorantes Fluorescentes , Simulación del Acoplamiento Molecular , Naftalimidas , Albúmina Sérica Bovina , Albúmina Sérica Humana , Espectrometría de Fluorescencia , Naftalimidas/química , Naftalimidas/síntesis química , Humanos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Albúmina Sérica Bovina/química , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Sitios de Unión , Bovinos , Estructura Molecular , Animales , Unión Proteica , Dicroismo Circular , Benzotiazoles/química , Benzotiazoles/síntesis química , Albúmina Sérica/química , Albúmina Sérica/metabolismo
8.
Future Med Chem ; 13(23): 2047-2067, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34672778

RESUMEN

Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti-Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.


Asunto(s)
Antifúngicos/farmacología , Candida tropicalis/efectos de los fármacos , Naftalimidas/farmacología , Tiazoles/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Naftalimidas/síntesis química , Naftalimidas/química , Tiazoles/síntesis química , Tiazoles/química
9.
J Inorg Biochem ; 220: 111466, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33933927

RESUMEN

In recent years, fluorescent sensors have emerged as attractive imaging probes due to their distinct responses toward bio-relevant metal ions. However, the bioimaging application main barrier is the 'turn-off' response toward paramagnetic metal ions such as Cu2+ under physiological conditions. Herein, we report a new sensor (2-methyl(4-bromo-N-ethylpiperazinyl-1,8-naphthalimido)-4-(1H-phenanthro[9,10-d]imidazole-2-yl) phenol)NPP with multifunctional (Naphthalimide, Piperazine, Phenanthroimidazole) units for fluorescent and colourimetric detection of Cu2+ in an aqueous medium. Both absorption and fluorescence spectral titration strategies were used to monitor the Cu2+-sensing property of NPP. The NPP displays a weak emission at ca. 455 nm, which remarkably enhances (⁓3.2-fold) upon selective binding of Cu2+ over a range of metal ions, including other paramagnetic metal ions (Mn2+, Fe3+, Co2+). The stoichiometry, binding constant (Ka) and the LOD (limit of detection) of NPP toward Cu2+ ions were found to be 1:1, 5.0 (± 0.2) × 104 M-1 and 6.5 (± 0.4) × 10-7 M, respectively. We have also used NPP as a fluorescent probe to detect Cu2+ in live (human cervical HeLa) cancer cells. The emission intensity of NPP was almost recovered in HeLa cells by incubating 'in situ' the derived Cu2+ complex (NPP-Cu2+) in the presence of a benchmark chelating agent such as EDTA (ethylenediaminetetraacetate). The fluorescent emission of NPP was reverted significantly in each cycle upon sequencial addition of Cu2+ and EDTA to the NPP solution. Overall, NPP is a novel, simple, economic and portable sensor that can detect Cu2+ in biological and environmental scenarios.


Asunto(s)
Cobre/análisis , Colorantes Fluorescentes/química , Imidazoles/química , Naftalimidas/química , Fenantrenos/química , Colorimetría/métodos , Colorantes Fluorescentes/síntesis química , Células HeLa , Humanos , Imidazoles/síntesis química , Límite de Detección , Microscopía Fluorescente , Naftalimidas/síntesis química , Fenantrenos/síntesis química , Espectrometría de Fluorescencia
10.
J Inorg Biochem ; 219: 111425, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33831713

RESUMEN

A series of tripodal ferrocenyl bis-naphthalimide derivatives were synthesized and characterized. All of the bis-naphthalimide derivatives exhibited good DNA binding ability which was confirmed by ethidium bromide (EB) displacement experiment and ultraviolet (UV)-visible absorption titration. And the binding mode of these compounds was proved to be a hybrid binding mode by experiments. The cytotoxicity of synthesized compounds against 4 different human cancer cell lines (EC109, BGC823, SGC7901 and HEPG2) was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. All of the bis-naphthalimide derivatives exhibited good anticancer activity than the positive control drug (amonafide), which was due to the promotion of reactive oxygen species (ROS) level in test cancer cells by the reversible one-electron redox process of ferrocenyl bis-naphthalimide derivatives. Although there was no obvious relationship between the binding constants and the chain length, the structure cytotoxicity relationship revealed that the linker of n = 3, m = 1 was the best choice for the tested tripodol bis-naphthalimide derivatives. SYNOPSIS: A series of tripodal ferrocenyl bis-naphthalimide derivatives were synthesized to study the DNA binding ability and the cytotoxicity induced by reactive oxygen species. All of the compounds exhibited good DNA binding ability. And the structure cytotoxicity relationship revealed that the structure of 5h was the best choice.


Asunto(s)
ADN/química , Compuestos Ferrosos/química , Naftalimidas/química , Adenina/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales/métodos , Electroquímica/métodos , Etidio/química , Citometría de Flujo/métodos , Humanos , Metalocenos/química , Estructura Molecular , Naftalimidas/síntesis química , Naftalimidas/farmacología , Organofosfonatos/farmacología , Especies Reactivas de Oxígeno , Relación Estructura-Actividad
11.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33803403

RESUMEN

We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides bearing ortho- or meta-carboranes exhibited diversified activity. Naphthalimides were more cytotoxic than naphthalic anhydrides, with the highest IC50 value determined for compound 9 (3.10 µM). These compounds were capable of inducing cell cycle arrest at G0/G1 or G2M phase and promoting apoptosis, autophagy or ferroptosis. The most promising conjugate 35 caused strong apoptosis and induced ROS production, which was proven by the increased level of 2'-deoxy-8-oxoguanosine in DNA. The tested conjugates were found to be weak topoisomerase II inhibitors and classical DNA intercalators. Compounds 33, 34, and 36 fluorescently stained lysosomes in HepG2 cells. Additionally, we performed a similarity-based assessment of the property profile of the conjugates using the principal component analysis. The creation of an inhibitory profile and descriptor-based plane allowed forming a structure-activity landscape. Finally, a ligand-based comparative molecular field analysis was carried out to specify the (un)favorable structural modifications (pharmacophoric pattern) that are potentially important for the quantitative structure-activity relationship modeling of the carborane-naphthalimide conjugates.


Asunto(s)
Antineoplásicos , Sustancias Intercalantes , Naftalimidas , Neoplasias , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Células Hep G2 , Humanos , Sustancias Intercalantes/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , Naftalimidas/síntesis química , Naftalimidas/química , Naftalimidas/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología
12.
Eur J Med Chem ; 210: 112951, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33109400

RESUMEN

Four series of new 3-nitro naphthalimides derivatives, 4(4a‒4f), 5(5a‒5i), 6(6a‒6e) and 7 (7a‒7j), were designed and synthesized as antitumor agents. Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective in vitro antiproliferative activity on SMMC-7721, T24, SKOV-3, A549 and MGC-803 cancer cell lines in comparison with 5-fluorouracil (5-FU), mitonafide and amonafide. Nude mouse xenotransplantation model assay results indicated that compounds 6b and 7b exhibited good in vivo antiproliferative activity in MGC-803 xenografts in comparison with amonafide and cisplatin, suggesting that compounds 6b and 7b could be good candidates for antitumor agents. Gel electrophoresis assay indicated that DNA and Topo I were the potential targets of compounds 6b and 7b, and comet assay confirmed that compounds 6b and 7b could induce DNA damage, while the further study showed that the 6b- and 7b-induced DNA damage was accompanied by the upregulation of p-ATM, P-Chk2, Cdc25A and p-H2AX. Cell cycle arrest studies demonstrated that compounds 6b and 7b arrested the cell cycle at the S phase, accompanied by the upregulation of the expression levels of the antioncogene p21 and the down-regulation of the expression levels of cyclin E. Apoptosis assays indicated that compounds 6b and 7b caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-3, caspase-9 and PARP and the downregulation of Bcl-2. These mechanistic studies suggested that compounds 6b and 7b exerted their antitumor activity by targeting to DNA, thereby inducing DNA damage and Topo I inhibition, and consequently causing S stage arrest and the induction of apoptosis.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Daño del ADN/efectos de los fármacos , Naftalimidas/química , Naftalimidas/farmacología , Animales , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/genética , Proliferación Celular/efectos de los fármacos , Diseño de Fármacos , Humanos , Ratones Desnudos , Naftalimidas/síntesis química , Neoplasias/tratamiento farmacológico , Neoplasias/genética
13.
J Chem Phys ; 153(14): 144302, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-33086833

RESUMEN

Directing energy and charge transfer processes in light-harvesting antenna systems is quintessential for optimizing the efficiency of molecular devices for artificial photosynthesis. In this work, we report a novel synthetic method to construct two regioisomeric antenna molecules (1-D2A2 and 7-D2A2), in which the 4-(n-butylamino)naphthalene monoimide energy and electron donor is attached to the perylene monoimide diester (PMIDE) acceptor at the 1- and 7-bay positions, respectively. The non-symmetric structure of PMIDE renders a polarized distribution of the frontier molecular orbitals along the long axis of this acceptor moiety, which differentiates the electron coupling between the donor, attached at either the 1- or the 7-position, and the acceptor. We demonstrate that directional control of the photo-driven charge transfer process has been obtained by engineering the molecular structure of the light-harvesting antenna molecules.


Asunto(s)
Naftalimidas/química , Perileno/análogos & derivados , Transferencia de Energía , Luz , Naftalimidas/síntesis química , Naftalimidas/efectos de la radiación , Perileno/efectos de la radiación , Electricidad Estática
14.
J Fluoresc ; 30(5): 977-983, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32761419

RESUMEN

A reaction-based sensor (NAS-1) showed a high affinity and sensitivity to HSO3- via a nucleophilic addition reaction in the aqueous media, giving dual signals from absorption and emission spectra. NAS-1 was successfully applied in RK13 epithelial cells to detect HSO3- in a cellular environment.


Asunto(s)
Colorantes Fluorescentes/química , Naftalimidas/química , Sulfitos/análisis , Animales , Células Cultivadas , Colorantes Fluorescentes/síntesis química , Estructura Molecular , Naftalimidas/síntesis química , Imagen Óptica , Conejos , Espectrometría de Fluorescencia
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 238: 118442, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32408229

RESUMEN

A series of 3-amino-N-substituted-1,8-naphthalimides and their salicylic Schiff base derivatives were synthesized. The structure of the obtained compounds was confirmed using 1H and 13C NMR, FT-IR spectroscopy and elemental analysis and COSY and HMQC for the representative molecules. The photophysical (UV-Vis, PL) and biological properties of all of the prepared compounds were studied. It was found that the amine with the n-hexyl group in EtOH had the highest PL quantum yield (Ф = 85%) compared to the others. Moreover, the chelating properties of the azomethines with the n-hexyl group (1a, 1b, 1c) were tested against various cations (Al3+, Ba2+, Co2+, Cu2+, Cr3+, Fe2+, Fe3+, Mn2+, Ni2+, Pb2+, Sr2+ and Zn2+) in an acetonitrile, acetone and PBS/AC mixture. Compounds that contained the electron withdrawing groups (-Br, -I) had the ability to chelate most of the studied cations, while the unsubstituted derivative chelated only the trivalent cations such as Al3+, Cr3+ and Fe3+ in acetonitrile. The effect of the environment on the keto-enol tautomeric equilibrium was also demonstrated, especially in the case of the derivative with a bromine atom. The biological studies showed that the tested molecules had no cytotoxicity. Additionally, the ability to image intracellular organelles such as the mitochondria and endoplasmic reticulum was revealed. The crucial role of the hydrolysis of imines for cellular imaging was presented.


Asunto(s)
Colorantes Fluorescentes/química , Naftalimidas/química , Retículo Endoplásmico/ultraestructura , Colorantes Fluorescentes/síntesis química , Células HCT116 , Humanos , Hidrólisis , Microscopía Fluorescente/métodos , Mitocondrias/ultraestructura , Naftalimidas/síntesis química , Imagen Óptica/métodos
16.
Anal Chim Acta ; 1116: 9-15, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32389192

RESUMEN

The malondialdehyde (MDA)-specific detection probe (MDA-6) was successfully synthesised through the photoinduced electron transfer (PET) mechanism which possesses many biological applications. In vivo biological applicability of this probe was proved in different cell lines, zebrafish and mice. In these models, the MDA was produced by oxygen stress injury and the relationship between MDA and probe were evaluated in vitro as well as in vivo under different stress conditions. After comparing evaluated results with commercial MDA kit, MDA-6 was concluded with high specificity, low limit of detection (0.03 µM), and can achieve micro-detection of MDA with low cytotoxicity, demonstrating MDA-6 enables safe and effective detection.


Asunto(s)
Colorantes Fluorescentes/química , Malondialdehído/sangre , Naftalimidas/química , Estrés Oxidativo/fisiología , Animales , Trióxido de Arsénico/toxicidad , Línea Celular Tumoral , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/toxicidad , Fluorometría , Humanos , Hipoxia/fisiopatología , Límite de Detección , Ratones , Daño por Reperfusión Miocárdica/fisiopatología , Naftalimidas/síntesis química , Naftalimidas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Pez Cebra
17.
Chemistry ; 26(44): 10064-10071, 2020 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-32428299

RESUMEN

Fluorescent sensors are a vital research tool, enabling the study of intricate cellular processes in a sensitive manner. The design and synthesis of responsive and targeted probes is necessary to allow such processes to be interrogated in the cellular environment. This remains a challenge, and requires methods for functionalisation of fluorophores with multiple appendages for sensing and targeting groups. Methods to synthesise more structurally complex derivatives of fluorophores will expand their potential scope. Most known 4-amino-1,8-naphthalimides are only functionalised at imide and 4-positions, and structural modifications at additional positions will increase the breadth of their utility as responsive sensors. In this work, methods for the incorporation of a hypoxia sensing group to 4-amino-1,8-naphthalimide were evaluated. An intermediate was developed that allowed us to incorporate a sensing group, targeting group, and ICT donor to the naphthalimide core in a modular fashion. Synthetic strategies for attaching the hypoxia sensing group and how they affected the fluorescence of the naphthalimide were evaluated by photophysical characterisation and time-dependent density functional theory. An extracellular hypoxia probe was then rationally designed that could selectively image the hypoxic and necrotic region of tumour spheroids. Our results demonstrate the versatility of the naphthalimide scaffold and expand its utility. This approach to probe design will enable the flexible, efficient generation of selective, targeted fluorescent sensors for various biological purposes.


Asunto(s)
1-Naftilamina/análogos & derivados , Colorantes Fluorescentes/análisis , Colorantes Fluorescentes/síntesis química , Hipoxia/metabolismo , Naftalimidas/química , Naftalimidas/síntesis química , Quinolonas/química , Quinolonas/síntesis química , 1-Naftilamina/análisis , 1-Naftilamina/síntesis química , 1-Naftilamina/química , Línea Celular , Colorantes Fluorescentes/química , Humanos , Naftalimidas/análisis , Quinolonas/análisis
18.
Analyst ; 145(11): 3878-3884, 2020 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-32297624

RESUMEN

As an important gasotransmitter, hydrogen sulfide having multiple biological roles cannot be easily probed in cells. In this study, a light controllable H2S donor, Nap-Sul-ONB, derived from naphthalimide was developed. Under the irradiation of 365 nm light, a readily controlled stimulus, the donor could release COS to form H2S and exhibit turn on fluorescence to indicate the release of payload and its cellular location. Besides, the ROS scavenging ability and cell protective effect of Nap-Sul-ONB against endogenous and exogenous ROS were studied. The results showed that upon 365 nm light irradiation, Nap-Sul-ONB could reduce the cellular ROS level and increase the survival rate of PMA-treated cells.


Asunto(s)
Depuradores de Radicales Libres/farmacología , Sulfuro de Hidrógeno/farmacología , Naftalimidas/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Óxidos de Azufre/farmacología , Supervivencia Celular/efectos de los fármacos , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/efectos de la radiación , Humanos , Sulfuro de Hidrógeno/química , Células MCF-7 , Naftalimidas/síntesis química , Naftalimidas/efectos de la radiación , Óxidos de Azufre/química , Acetato de Tetradecanoilforbol/farmacología , Rayos Ultravioleta
19.
Chempluschem ; 85(4): 689-693, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32253834

RESUMEN

The preparation and characterization of new functional materials for sensing have an important role in clinical diagnosis. Monitoring the surface functionalization of functional material is crucial because the final sensing properties are affected by how the (bio)molecules are immobilized on the surface of solid supports. Here, a new approach for the preparation of functional materials for biomedical diagnosis was developed. This method employs a fluorescent dye comprising 4-amino-1,8-naphthalimide with two orthogonal functional groups suitable for click chemistry. The orthogonal reactivity of these groups allows the sequential functionalization of the fluorophore, firstly with (bio)molecules, and then binding of the (bio)molecule-naphthalimide macrostructure onto the surface of a solid support. The fluorescent properties confirm the immobilization of the (bio)molecule on the surface of the solid support, without requiring other indirect methods to verify the immobilization. These functional materials were tested successfully with sera of patients, thus proving their potential application for allergic drug diagnosis.


Asunto(s)
Hipersensibilidad a las Drogas/diagnóstico , Colorantes Fluorescentes/química , Naftalimidas/química , Química Clic , Colorantes Fluorescentes/síntesis química , Humanos , Naftalimidas/síntesis química
20.
Bioorg Chem ; 96: 103631, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32036164

RESUMEN

The synthesis and characterization of a series of naphthalimide and phenanthro[9,10-d]imidazole conjugate is described. These compounds are evaluated in vitro for their cytotoxicity towards 60 human cancer cell lines. Derivative 16 shows excellent cytotoxic activity against these cancer cell lines with the range of growth inhibition from -55.78 to 94.53. The most potent derivative (ethylpiperazine, 16) is further studied to evaluate the interaction with ct-DNA using absorption and emission spectroscopy as well as DNA viscosity measurement. The DNA binding studies indicate that compound 16 is significantly interacted with DNA through groove binding having binding constant value of 7.81 × 104 M-1 alongwith partial intercalation between the base pairs of DNA strands. Further, topoisomerase inhibition study suggests that compound 16 is induced apoptosis and inhibits human topoisomerase (Topo-IIα) as a possible intracellular target. Molecular docking study of compound 16 with ct-DNA shows good docking score.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Naftalimidas/química , Naftalimidas/farmacología , Inhibidores de Topoisomerasa II/química , Inhibidores de Topoisomerasa II/farmacología , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , ADN/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Imidazoles/síntesis química , Imidazoles/química , Imidazoles/farmacología , Simulación del Acoplamiento Molecular , Naftalimidas/síntesis química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Fenantrenos/síntesis química , Fenantrenos/química , Fenantrenos/farmacología , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II/síntesis química
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