RESUMEN
ß-D-N4-hydroxycytidine (NHC, EIDD-1931) is a nucleoside analogue that exhibits broad spectrum antiviral activity against a variety of RNA viruses. Herein, we report the synthesis of a series of lipid prodrugs of NHC and a novel 3'-fluoro modified NHC analogue, and evaluation of their antiviral activity against five variants of SARS-CoV-2. All lipid prodrugs showed potent antiviral activity against the tested SARS-CoV-2 variants with EC50 values in the range of 0.31-3.51 µM, which were comparable to those of NHC or higher than those of remdesivir and molnupiravir. An increase in the cytostatic activity of the lipid prodrugs was found, but prodrug 2d proved equally selective as molnupinavir. The 3'-F analogue of NHC (6) only displayed minor antiviral activity against the SARS-CoV-2 Omicron variant (EC50 = 29.91 µM), while no activity was found for other variants at the highest concentration tested. The promising antiviral data of the lipid prodrugs of NHC suggest that they deserve further investigation as new anti-SARS-CoV-2 drugs.
Asunto(s)
COVID-19 , Profármacos , Humanos , SARS-CoV-2 , Profármacos/farmacología , Antivirales/farmacología , Antivirales/uso terapéutico , LípidosRESUMEN
BU-4664L is a naturally occurring N-farnesylated dibenzodiazepinone with important biological activities. Herein, we report the synthesis and antitumor evaluation of two series of BU-4664L derivatives bearing different substituent patterns on the dibenzodiazepinone core and with diverse side chains. All of the derivatives displayed micromolar activity against the human prostate cancer PC-3 cells, while lower or no activity against the human lung H460 cells. The most active derivatives were 10a and 16c which exerted antiproliferative activity against PC-3 cells with GI50 values of 5.66 and 5.94 µM, respectively, and thus represent promising lead compounds for further development.
Asunto(s)
Antineoplásicos/farmacología , Dibenzazepinas/farmacología , Sesquiterpenos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dibenzazepinas/síntesis química , Dibenzazepinas/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Sesquiterpenos/síntesis química , Sesquiterpenos/química , Relación Estructura-ActividadRESUMEN
The possibility of determination of tofu hardness by near infrared spectroscopy (NIR, 833-2500 nm) was studied. The influences of water content and protein content on the spectra were discussed, in order to detect the hardness. The models of Tofu hardness were calibrated by partial least squares regression (PLS) after eliminating outline, spectra pretreatment, and wavelength optimization (r = 0.994, RMSEC = 0.391%, RMSEP = 0.416%, RSD = 2.27%). All of the results were better than those by sense assessing method.