Abietic, maleopimaric and quinopimaric dipeptide Ugi-4CR derivatives and their potency against influenza A and SARS-CoV-2
E. V. Tret’yakova, Xinyuan Ma, О. Б. Казакова, Анна А. Штро, Galina Petukhova, Anna Smirnova, Huan Xu, Sulong Xiao
Abstract
A set of 12 abietane diterpene derivatives have been synthesised by the Ugi-four component reaction (Ugi-4CR) and tested for cytotoxicity and activity against influenza virus A/Puerto Rico/8/34 (H1N1) and SARS-CoV-2 pseudovirus. Five dipeptide derivatives demonstrated a selectivity index (SI) higher than 10 and IC50 values from 2 to 32 μM against influenza virus. Compound 11 was found to be a lead with SI of 200, and time-of-addition experiments showed the viral entry into the cell and the binding of the virus to the receptor as a possible target. Compound 7 was the only one showed weak anti-SARS-CoV-2 activity with EC50 value of 80.96 µM. Taken together, our data suggest the potency of diterpene acids-Ugi products as new effective anti-influenza compounds.