Molecular Umbrella as a Nanocarrier for Antifungals

Abstract

A molecular umbrella composed of two O-sulfated cholic acid residues was applied for the construction of conjugates with cispentacin, containing a “trimethyl lock” (TML) or o-dithiobenzylcarbamoyl moiety as a cleavable linker. Three out of five conjugates demonstrated antifungal in vitro activity against C. albicans and C. glabrata but not against C. krusei, with MIC90 values in the 0.22–0.99 mM range and were not hemolytic. Antifungal activity of the most active conjugate 24c, containing the TML–pimelate linker, was comparable to that of intact cispentacin. A structural analogue of 24c, containing the Nap-NH2 fluorescent probe, was accumulated in Candida cells, and TML-containing conjugates were cleaved in cell-free extract of C. albicans cells. These results suggest that a molecular umbrella can be successfully applied as a nanocarrier for the construction of cleavable antifungal conjugates.

Searching for Conjugates as New Structures for Antifungal Therapies

“…In vitro , its activity was assessed in the MIC 90 range of 0.22–0.99 mM against C. albicans and C. glabrata (Table ). Skwarecki et al showed that conjugates containing a dihedral molecular umbrella can penetrate the cell wall in Candida cells. This allows further research to construct more active conjugates with molecules other than cispentacin. , …”

“… Skwarecki et al showed that conjugates containing a dihedral molecular umbrella can penetrate the cell wall in Candida cells. This allows further research to construct more active conjugates with molecules other than cispentacin. , …”

“…This allows further research to construct more active conjugates with molecules other than cispentacin. 100,106 3.6. Siderophores in Antifungal Therapy.…”

Carbon Nanotube Hybrid Materials: Efficient and Pertinent Platforms for Antifungal Drug Delivery

“…[9,10] Candidiasis has been investigated as the most common mycosis, and C. albicans has been ranked as the fourth most common causative organism of nosocomial infections (Candidiasis) globally. [11][12][13] Although currently, available antifungal drugs such as polyenes, azoles, allylamines, echinocandins, and antimetabolites have been helpful in many circumstances, they suffer from a confluence of systemic toxicities (such as hydrophobicity, poor pharmacokinetics, and -dynamics, low bioavailability, systemic side effects) and escalating resistance that hinders their therapeutic efficiency. [14] These limitations of existing antifungal drugs have been overcome by formulation methods of novel antifungal drugs, [14] improvements of existing antifungal drugs, [14] combination therapy, [14] and efficient delivery approaches for antifungal drugs.…”