9 research outputs found
Silver nanoparticle-catalysed phenolysis of epoxides under neutral conditions: Scope and limitations of metal nanoparticles and applications towards drug synthesis
Chemo- and regio-selective epoxide phenolysis is reported for the first time under neutral condition catalysed by silver nanoparticles. Other metal nanoparticles (e.g., Au, Pd, Cu, In, and Ru) are less effective. The choice of solvent is critical with 2-propanol being the best followed by DEF. Amongst various stabilisers used (surfactants, PEGs, tetra-alkylammonium halides) the tetra-alkylammonium halides are found to be the most effective (TBAF > TBAB > TBACl > TBAI). The role of the silver nanoparticles is envisaged as synchronous mode epoxide-phenol dual activation via a cooperative network of coordination, anionâÏ interaction, and hydrogen bond. The silver nanoparticles are recovered and reused for five consecutive times. The reaction has been used for the synthesis of propranolol and naftopidil as a few representative cardiovascular drugs
Toward a Template for Synthetic Actin-Targeting Macrolide Analogues That Inhibit Cancer Cell Invasiveness
Actin barbed end-binding macrolides have been shown to
inhibit
cancer cell motility and invasion of extracellular matrix (ECM), evoking
their potential utility as therapies for metastatic cancers. Unfortunately,
the direct use of these compounds in clinical settings is impeded
by their limited natural abundance, challenging total synthesis, and
detrimental effects on normal tissues. To develop potent analogues
of these compounds that are simpler to synthesize and compatible with
cell-specific targeting systems, such as antibodies, we designed over
20 analogues of the acyclic side chain (tail) of the macrolide Mycalolide
B. These analogues probed the contributions of four distinct regions
of the tail towards the inhibition of actin polymerization and ECM
invasion by human lung cancer A549 cells. We observed that two of
these regions tolerate considerable substituent variability, and we
identified a specific combination of substituents that leads to the
optimal inhibition of the ECM invasion activity of A549 cells
Toward a Template for Synthetic Actin-Targeting Macrolide Analogues That Inhibit Cancer Cell Invasiveness
Actin barbed end-binding macrolides have been shown to
inhibit
cancer cell motility and invasion of extracellular matrix (ECM), evoking
their potential utility as therapies for metastatic cancers. Unfortunately,
the direct use of these compounds in clinical settings is impeded
by their limited natural abundance, challenging total synthesis, and
detrimental effects on normal tissues. To develop potent analogues
of these compounds that are simpler to synthesize and compatible with
cell-specific targeting systems, such as antibodies, we designed over
20 analogues of the acyclic side chain (tail) of the macrolide Mycalolide
B. These analogues probed the contributions of four distinct regions
of the tail towards the inhibition of actin polymerization and ECM
invasion by human lung cancer A549 cells. We observed that two of
these regions tolerate considerable substituent variability, and we
identified a specific combination of substituents that leads to the
optimal inhibition of the ECM invasion activity of A549 cells