2 research outputs found
Identification of Novel Aurora Kinase A (AURKA) Inhibitors via Hierarchical Ligand-Based Virtual Screening
Aurora
kinases are essential for cell mitosis, amplified, and overexpressed
in various human malignancies. Therefore, Aurora kinases have been
promising targets for anticancer therapies, which has prompted an
intensive search for their small-molecule inhibitors. In this work,
we performed a hierarchical and time-efficient virtual screening cascade
for scaffold hopping, aiming to obtain structurally novel and highly
potent hit compounds targeting Aurora kinases. The cascade consisted
of a shape- and an electrostatic-based protocol, combined with a QSAR-based
selection protocol. This virtual screening cascade was used to screen
two databases, one commercial database named the J&K database
containing about 5.2 million diverse molecules and the Drugbank database.
Experimental validations led to the identification of one structurally
novel and highly potent hit compound (hit 1, found to possess an IC<sub>50</sub> of 8.1 and 19 nM for Aurora kinases A and B, respectively),
which can be a promising starting point for further exploration. Additionally,
Aurora kinases were identified as off-targets for hits 2–6
(Crizotinib, CI-1033, Dasatinib, Bosutinib, MLN-518), which are approved
or investigational drugs as listed in Drugbank, plausibly suggesting
targeting Aurora kinases may even contribute to their mechanism of
action
Efficient Control of Rhizoctonia solani Using Environmentally Friendly pH-Responsive Tannic Acid–Rosin Nano-Microcapsules
A nanomicrocapsule system was constructed
through the
polymerization
of tannic acid (TA) and emulsifier OP-10 (OP-10), followed by the
chelation of iron ions, to develop a safe and effective method for
controlling Rhizoctonia solani in agriculture.
The encapsulated active component is a rosin-based triazole derivative
(RTD) previously synthesized by our research group (RTD@OP10-TA-Fe).
The encapsulation efficiency of the nanomicrocapsules is 82.39%, with
an effective compound loading capacity of 96.49%. Through the encapsulation
of the RTD via nanomicrocapsules, we improved its water solubility,
optimized its stability, and increased its adhesion to the leaf surface.
Under acidic conditions (pH = 5.0), the release rate of nanomicrocapsules
at 96 h is 96.31 ± 0.8%, which is 2.04 times higher than the
release rate under normal conditions (pH = 7.0). Additionally, the
results of in vitro and in vivo antifungal
assays indicate that compared with the original compound, the nanomicrocapsules
exhibit superior antifungal activity (EC50 values of RTD
and RTD@OP10-TA-Fe are 1.237 and 0.860 mg/L, respectively). The results
of field efficacy trials indicate that compared with RTD, RTD@OP10-TA-Fe
exhibits a more prolonged period of effectiveness. Even after 3 weeks,
the antifungal rate of RTD@OP10-TA-Fe remains at 40%, whereas RTD,
owing to degradation, shows an antifungal rate of 11.11% during the
same period. Furthermore, safety assessment results indicate that
compared with the control, RTD@OP10-TA-Fe has almost no impact on
the growth of rice seedlings and exhibits low toxicity to zebrafish.
This study provides valuable insights into controlling R. solani and enhancing the compound performance