4 research outputs found
Prediction of Drug-Induced Nephrotoxicity with a Hydroxyl Radical and Caspase Light-Up Dual-Signal Nanoprobe
The
development of well-designed nanoprobes for specific imaging
of multiple biomarkers in renal cells will afford beneficial information
related to the transmutation process of drug-induced kidney injury
(DIKI). However, the most reported nanoprobes for DIKI detection were
dependent on single-signal output and lack of kidney targeting. In
this work, we reported a renal cell targeting and dual-signal nanoprobe
by encapsulating Brite 670 and Dabcyl-KFFÂFÂDÂEÂVDK-FAM
into a low molecular weight chitosan nanoparticle. Confocal fluorescence
imaging results demonstrated that the nanoprobe could visualize the
upregulation of hydroxyl radical in early stage and activation of
caspase-3 in late stage of DIKI at both the renal cell and tissue
level. In a mouse DIKI model, the positive time of 8 h using nanoprobe
imaging was superior to that of 72 h for serum creatinine or blood
urea nitrogen, 16 h for cystatin-C, and 24 h for kidney injury molecule-1
with conventional methods. These results demonstrated that the nanoprobe
may be a promising tool for effective early prediction and discriminative
imaging of DIKI
Prediction of Drug-Induced Nephrotoxicity with a Hydroxyl Radical and Caspase Light-Up Dual-Signal Nanoprobe
The
development of well-designed nanoprobes for specific imaging
of multiple biomarkers in renal cells will afford beneficial information
related to the transmutation process of drug-induced kidney injury
(DIKI). However, the most reported nanoprobes for DIKI detection were
dependent on single-signal output and lack of kidney targeting. In
this work, we reported a renal cell targeting and dual-signal nanoprobe
by encapsulating Brite 670 and Dabcyl-KFFÂFÂDÂEÂVDK-FAM
into a low molecular weight chitosan nanoparticle. Confocal fluorescence
imaging results demonstrated that the nanoprobe could visualize the
upregulation of hydroxyl radical in early stage and activation of
caspase-3 in late stage of DIKI at both the renal cell and tissue
level. In a mouse DIKI model, the positive time of 8 h using nanoprobe
imaging was superior to that of 72 h for serum creatinine or blood
urea nitrogen, 16 h for cystatin-C, and 24 h for kidney injury molecule-1
with conventional methods. These results demonstrated that the nanoprobe
may be a promising tool for effective early prediction and discriminative
imaging of DIKI
Synthesis of Natural Acylphloroglucinol-Based Antifungal Compounds against <i>Cryptococcus</i> Species
Thirty-three natural-product-based
acylphloroglucinol derivatives
were synthesized to identify antifungal compounds against <i>Cryptococcus</i> spp. that cause the life-threatening disseminated
cryptococcosis. In vitro antifungal testing showed that 17 compounds
were active against <i>C. neoformans</i> ATCC 90113, <i>C. neoformans</i> H99, and <i>C. gattii</i> ATCC 32609,
with minimum inhibitory concentrations (MICs) in the range 1.0–16.7
μg/mL. Analysis of the structure and antifungal activity of
these compounds indicated that the 2,4-diacyl- and 2-acyl-4-alkylphloroglucinols
were more active than <i>O</i>-alkyl-acylphloroglucinols.
The most promising compound found was 2-methyl-1-(2,4,6-trihydroxy-3-(4-isopropylbenzyl)Âphenyl)Âpropan-1-one
(<b>11j</b>), which exhibited potent antifungal activity (MICs,
1.5–2.1 μg/mL) and low cytotoxicity against the mammalian
Vero and LLC-PK1 cell lines (IC<sub>50</sub> values >50 μg/mL).
This compound may serve as a template for further synthesis of new
analogues with improved antifungal activity. The findings of the present
work may contribute to future antifungal discovery toward pharmaceutical
development of new treatments for cryptococcosis
Antibacterial Prenylated Acylphloroglucinols from <i>Psorothamnus fremontii</i>
Psorothatins A–C (<b>1</b>–<b>3</b>),
three antibacterial prenylated acylphloroglucinol derivatives, were
isolated from the native American plant <i>Psorothamnus fremontii</i>. They feature an unusual α,β-epoxyketone functionality
and a β-hydroxy-α,β-unsaturated ketone structural
moiety. The latter forms a pseudo-six-membered heterocyclic ring due
to strong intramolecular hydrogen bonding, as indicated by the long-range
proton–carbon correlations in the NMR experiments. Psorothatin
C (<b>3</b>) was the most active compound against methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant <i>Enterococcus
faecium</i>, with IC<sub>50</sub> values in the range 1.4–8.8
μg/mL. The first total synthesis of <b>3</b> described
herein permits future access to structural analogues with potentially
improved antibacterial activities