Identification of Novel 5,6-Dimethoxyindan-1-one Derivatives as Antiviral Agents.
BACKGROUND
Discovery of novel antiviral agents is essential because viral infection continues to threaten human life globally. Various heterocyclic small molecules have been developed as antiviral agents. The 5,6-dimethoxyindan-1-on nucleus is of considerable interest as this ring is the key constituent in a range of bioactive compounds, both naturally occurring and synthetic, and often of considerable complexity.


OBJECTIVE
The main purpose of this research was to discover and develop small molecule heterocycles as broad-spectrum of antiviral agents.


METHOD
A focused small set of 5,6-dimethoxyindan-1-one analogs (6-8) along with a thiopene derivative (9) was screened for selected viruses (Vaccinia virus - VACA, Human papillomavirus - HPV, Zika virus - ZIKV, Dengue virus - DENV, Measles virus - MV, Poliovirus 3 - PV, Rift Valley fever virus - RVFV, Tacaribe virus - TCRV, Venezuelan equine encephalitis virus - VEEV, Herpes simplex virus 1 -HSV-1 and Human cytomegalovirus - HCMV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program.


RESULTS
These molecules demonstrated moderate to excellent antiviral activity towards variety of viruses. The 5,6-dimethoxyindan-1-one analog (7) demonstrated high efficacy towards vaccinia virus (EC50: <0.05 µM) and was nearly 232 times more potent than the standard drug Cidofovir (EC50: 11.59 µM) in primary assay whereas it demonstrated moderate activity (EC50: >30.00 µM) in secondary plaque reduction assay. The thiophene analog (9) has shown very good viral inhibition towards several viruses such as Human papillomavirus, Measles virus, Rift Valley fever virus, Tacaribe virus and Herpes simplex virus 1.


CONCLUSION
Our research identified a novel 5,6-dimethoxyindan-1-one analog (compound 7), as a potent antiviral agent for vaccinia virus, and heterocyclic chalcone analog (compound 9) as a broad spectrum antiviral agent.
['Patil|Siddappa A|SA|', 'Patil|Vikrant|V|', 'Patil|Renukadevi|R|', 'Beaman|Kenneth|K|', 'Patil|Shivaputra A|SA|']
D000998:Antiviral Agents D004305:Dose-Response Relationship, Drug D007189:Indans D008826:Microbial Sensitivity Tests D015394:Molecular Structure D013329:Structure-Activity Relationship D014780:Viruses
antiviral virus NIAID 5 6-Dimethoxyindan-1-one HIV in vitro screening ketone