Synthesis and bioevaluation of water-soluble ß-cyclodextrin-diterpene acid conjugates.

ABSTRACT

A series of ß-cyclodextrin (ß-CD)-conjugates were prepared by combining three abietane-type diterpene acids with two azide-functionalized ß-CDs via click chemistry, and the antiviral activity against wild-type and omicron SARS-CoV-2 spike pseudovirus as well as the antibacterial activity against Escherichia coli were investigated. All the synthesised conjugates exhibited no significant cytotoxicity to BHK-21-hACE2 cells with cell viability over 80% at concentration of 15 µM. Among the conjugates, the heptavalent ß-CD-dehydroabietic acid conjugate 6b exhibited higher anti-SARS-CoV-2 activity against the omicron variant compared to the other conjugates. This study suggested that the multivalent diterpene acid derivatives may have potential application against coronaviruses as entry inhibitors.