Synthesis and antiviral evaluation of new spiro compounds

Çınar G., Cihan Üstündağ G.

11. International Drug Chemistry Conference, Antalya, Turkey, 9 - 12 March 2023, pp.84

  • Publication Type: Conference Paper / Summary Text
  • City: Antalya
  • Country: Turkey
  • Page Numbers: pp.84
  • Istanbul University Affiliated: Yes


Seasonal influenza is a major public health problem caused by globally circulating influenza A and B
viruses. To face the emerging resistance to presently available drugs for the treatment of influenza
virus infections, new anti-influenza drugs, preferably with different mechanisms of action, are needed
(1). A class of influenza virus fusion inhibitors with N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide
scaffold and strong activity against H3 hemagglutinin (HA) have been identified previously (2-5). These
compounds were found to interfere with HA-mediated fusion of the influenza virus. In this context, we
have designed and synthesized new spiro analogues carrying a substituted benzamide function. The
structures of obtained compounds were established by using spectroscopic and microanalytical data.
The compounds were tested for in  vitro antiviral activity against selected DNA and RNA viruses in
MDCK, CRFK, Vero, HEL, HeLa and MT-4 cells. One derivative exhibited good in vitro inhibition against
influenza A/H3N2 virus at low micromolar concentration. The mechanism of action was elucidated by
performing HA-mediated fusion (syncytium formation) assay. The result of this test indicated that the
compound blocks hemagglutinin mediated membrane fusion as the previously reported counterparts.