Synthesis and bioevaluation of water-soluble β-cyclodextrin–diterpene acid conjugates

Abstract

A series of β-cyclodextrin (β-CD)-conjugates were prepared by combining three abietane-type diterpene acids with two azide-functionalized β-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 β-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.

Graphical Abstract

Keywords:

• Abietane diterpenoids
• abietic acid
• dehydroabietic acid
• dihydroquinopimaric acid
• β-cyclodextrin
• anticoronavirus
• antibacterial
• synthesis

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research by the Russian State-funded budget project No.1021062311392-9-1.4.1 in the development of basic methods and funded by the International Cooperation and Exchange Program by RFBR and NSFC (NSFC-RFBR) (grant no. 20-53-55001 to E. Tretyakova and grant no. 82161148006 to S. Xiao) and the National Natural Science Foundation of China (grant no. 22377006 to S. Xiao).