2 research outputs found
Quantitative Analysis the Weak Non-Covalent Interactions of the Polymorphs of Donepezil
Donepezil has polymorphism. Different crystalline forms
can exhibit
different physicochemical properties and biological activities. Exploration
of intermolecular interactions is essential to reveal the formation
mechanism and differences in properties of polymorphs. This study
explores the weak non-covalent intermolecular interactions of donepezil
polymorphs through fully ab initio quantum mechanical methods, semi-empirical
methods, and Hirshfeld surface analysis. The results show that the
Hirshfeld surface analysis method can clearly and intuitively reveal
the intermolecular interactions. Theoretical calculations using the
atom–atom Coulomb–London–Pauli (AA-CLP) method
were also performed to understand the interaction energies toward
the total lattice energy. The value of the lattice energy was in accordance
with the melting points of the donepezil polymorphs and brought to
light the nature of thermal stability. In the specific energy distribution,
the contribution of the dispersion force is the most prominent. Further
interaction energy analysis found that within a distance of 3.8 Ă…
from the center of the donepezil molecule, different crystalline forms
of donepezil molecules have different interaction energies with surrounding
molecules. The different interaction energies between polymorphs may
lead to polymorphs with different physical–chemical properties
Identification of Less Lipophilic Riminophenazine Derivatives for the Treatment of Drug-Resistant Tuberculosis
Clofazimine (CFZ), a member of the riminophenazine class,
has been studied in clinical trials for the treatment of multidrug-resistant
tuberculosis (MDR-TB). CFZ has several side effects which can be attributed
to its extremely high lipophilicity. A series of novel riminophenazine
analogues bearing a C-2 pyridyl substituent was designed and synthesized
with the goal of maintaining potent activity against Mycobacterium tuberculosis (M. tuberculosis) while improving upon its safety profile by lowering the lipophilicity.
All compounds were evaluated for their in vitro activity and cytotoxicity.
The results demonstrated that many new compounds had potent activity
against M. tuberculosis with MICs of
less than 0.03 ÎĽg/mL and low cytotoxicity with IC<sub>50</sub> values greater than 64 ÎĽg/mL. Some compounds were tested for
in vivo efficacy against MDR-TB in an experimental mouse infection
model. Two compounds demonstrated equivalent or better efficacy than
CFZ in this model with significantly reduced skin discoloration potential