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Due to the excellent characteristics of fluorescence-based imaging, such as non-invasive detection of biomarkers in vitro and in vivo with high sensitivity, good spatio-temporal resolution and fast response times, it has shown significant prospects in various applications. Compounds with both biological activities and fluorescent properties have the potential for integrated diagnosis and treatment application. Alectinib and Rilpivirine are two excellent drugs on sale that represent a clinically approved targeted therapy for ALK-rearranged NSCLC and have exhibited more favorable safety and tolerance profiles in Phase III clinical trials, ECHO and THRIVE, respectively. The optical properties of these two drugs, Alectinib and Rilpivirine, were deeply explored, firstly through the simulation of molecular structures, electrostatic potential, OPA/TPA and emission spectral properties and experiments on UV-vis spectra, fluorescence and cell imaging. It was found that Alectinib exhibited 7.8% of fluorescence quantum yield at the 450 nm excited wavelength, due to a larger electronic transition dipole moment (8.41 Debye), bigger charge transition quantity (0.682 e) and smaller reorganization energy (2821.6 cm-1). The stronger UV-vis spectra of Rilpivirine were due to a larger electron-hole overlap index (Sr: 0.733) and were also seen in CDD plots. Furthermore, Alectinib possessed obvious active two-photon absorption properties (δmaxTPA* Ï = 201.75 GM), which have potential TPA imaging applications in bio-systems. Lastly, Alectinib and Rilpivirine displayed green fluorescence in HeLa cells, suggesting the potential ability for biological imaging. Investigation using theoretical and experimental methods is certainly encouraged, given the particular significance of developing integrated diagnosis and treatment.
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Neoplasias Pulmonares , Rilpivirina , Humanos , Células HeLa , Carbazoles/farmacologíaRESUMEN
The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CLpro) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8H-indeno[1,2-d]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CLpro. Among them, the representative compound 7a displayed inhibitory activity with an IC50 of 1.28 ± 0.17 µM against SARS-CoV-2 3CLpro. Molecular docking of 7a against 3CLpro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CLpro.
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Tratamiento Farmacológico de COVID-19 , Inhibidores de Proteasas , Cisteína Endopeptidasas/química , Humanos , Simulación del Acoplamiento Molecular , Pandemias , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , SARS-CoV-2 , Tiazoles/farmacología , Proteínas Virales/metabolismoRESUMEN
Endometrial cancer (EC) is a common malignancy among women worldwide, and its recurrence makes it a common cause of cancer-related death. Surgery and external radiation, chemotherapy, or a combination of strategies are the cornerstone of therapy for EC patients. However, adjuvant treatment strategies face certain drawbacks, such as resistance to chemotherapeutic drugs; therefore, it is imperative to explore innovative therapeutic strategies to improve the prognosis of EC. With the development of pathology and pathophysiology, several biological targets associated with EC have been identified, including PI3K/Akt/mTOR, PARP, GSK-3ß, STAT-3, and VEGF. In this review, we summarize the progress of small molecule targeted therapies in terms of both basic research and clinical trials and provide cases of small molecules combined with fluorescence properties in the clinical applications of integrated diagnosis and treatment. We hope that this review will facilitate the further understanding of the regulatory mechanism governing the dysregulation of oncogenic signaling in EC and provide insights into the possible future directions of targeted therapeutic regimens for EC treatment by developing new agents with fluorescence properties for the clinical applications of integrated diagnosis and treatment.
RESUMEN
BACKGROUND & OBJECTIVE: The pathogenesis of endometrial carcinoma has not been clear yet. The aim of this study was to investigate the influence of expression of CD44v6, bcl-2, and vascular endothelial growth factor (VEGF) on oncogenesis and progression in endometrial carcinoma. METHODS: The expression levels of CD44v6, bcl-2, and VEGF were determined using immunohistochemistry in 55 cases with endometrial adenocarcinoma, 10 cases each of normal proliferative endometrium, simple hyperplasia, and atypical hyperplasia, respectively. RESULTS: (1)The expression of CD44v6 and VEGF increased gradually from normal proliferative endometrium to simple hyperplasia, atypical hyperplasia,and adenocarcinoma, which showed highly significant difference (P< 0.001, P< 0.001), whose ratios were 10%, 40%, 60%, 78.18% and 0%, 0%, 10%, 83.64%,respectively. While the expression of bcl-2 showed no significant difference among the above different tissues. (2)The CD44v6 expression in endometrial carcinoma was inversely associated with surgical stages and lymph node metastasis(P< 0.05, P< 0.01). The bcl-2 expression was found to be significantly related to histologic grades of the tumor (P< 0.05). The VEGF expression was significantly associated with surgical stages, myometrial invasion, and lymph node status. (3)There was statistically significant correlation between bcl-2 and CD44v6, bcl-2 and VEGF expression (P< 0.05, P< 0.05). (4)The univariate analysis revealed that the expression of CD44v6 and bcl-2 were significantly related to the prognosis of the patients (P< 0.01, P< 0.05). Cox proportional hazards model analysis showed that the prognosis was independently affected by age, surgical stage, and CD44v6 expression. CONCLUSION: CD44v6, bcl-2, and VEGF play roles in oncogenesis and progression of endometrial adenocarcinoma. Detection of these gene proteins may be helpful for early diagnosis, prognosis prediction, and treatment of endometrial carcinoma.