Implantable HDAC-inhibiting chemotherapeutics derived from hydrophobic amino acids for localized anticancer therapy

Abstract

Epigenetic targeting of different cancers by inhibiting particular histone deacetylase (HDAC) isozymes is a promising treatment approach against cancer. Development of locally-implantable molecular inhibitor of HDAC (called HDACi henceforth) promise...

Divergent self-assembly propensity of enantiomeric phenylalanine amphiphiles that undergo pH-induced nanofiber-to-nanoglobule conversion

“…We have been exploring the self-assembly of naphthaleneappended phenylalanine (NapF) derivatives to create various low molecular weight organo-and hydro-gelators (LMHGs) of biomedical utility. 1,18,28,44,45,47 The self-assembly of these LMHGs is mainly governed by CH-p interactions between the aromatic residues and H-bonding interactions between the amide residues of the molecules. During these investigations, we observed that the enantiomeric NapF-EDA amphiphiles begin to form self-supporting hydrogels at different concentrations.…”

“…1,28,43 For example, single-F PDAs containing a hydroxamic acid residue are not only efficient molecular hydrogelators but also potently inhibit histone deacetylase (HDAC) enzymes involved in epigenetic control of cell functioning and cancer progression. 44 Other single F-PDAs could bind with Au(III) ions to engender the production of reactive oxygen species (ROS) leading to anticancer abilities. 45 Khushalani and co-workers observed that a single F system was capable of forming nano-fibrillar structures which were not present in the case of other amino acids like Tyr.…”

Anion-responsive self-assembled hydrogels of a phenylalanine–TREN conjugate allow sequential release of propranolol and doxorubicin

“…The rotational flexibility of aromatic residues in naphthaleneappended phenylalanine (NapF) derivatives has been utilized in the past to create potent molecular hydrogelators. 2,4,12,54 To impart an anion-responsive character to the NapF hydrogelators, we appended polyamine residues to NapF by employing the aminolysis of the NapF-OMe ester by the respective amine. This easy-to-execute protocol was used to prepare three molecules viz.…”

“…[9][10][11] Specially designed PDAs also demonstrate potent anticancer performance, either through HDAC inhibition or by generation of reactive oxygen species (ROS) in the presence of Au(III) ions. 4,12 The nanofibrillar self-assemblies of some PDAs can entrap solvent (or water) molecules to form supramolecular (hydro)gels that exhibit thermoreversibility, biocompatibility, biodegradability and tunability of nanostructures, which is needed in tissue engineering as well as in precision drug delivery applications. [13][14][15][16][17][18][19][20][21][22] Multiple noncovalent interactions such as hydrogen bonding, van der Waals inter-actions, π-π stacking, 23 hydrophobic interactions, 24 and even metal-coordination 25,26 are employed to stabilize these selfassemblies.…”