title: Identification of Novel 5,6-Dimethoxyindan-1-one Derivatives as Antiviral Agents.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Bangalore 562112, Karnataka. India.
authors.forename: Siddappa A
authors.initials: SA
authors.lastname: Patil
authors.affiliation: Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Bangalore 562112, Karnataka. India.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Patil
authors.affiliation: Pharmaceutical Sciences Department, College of Pharmacy, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064. United States.
authors.forename: Renukadevi
authors.initials: R
authors.lastname: Patil
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064. United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Beaman
authors.affiliation: Pharmaceutical Sciences Department, College of Pharmacy, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064. United States.
authors.forename: Shivaputra A
authors.initials: SA
authors.lastname: Patil
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014780:Viruses / Q000187:drug effects*
chemical_list: C000625165:5,6-dimethoxyindan-1-one; D000998:Antiviral Agents; D007189:Indans
keywords: 5; 6-Dimethoxyindan-1-one; HIV; NIAID; antiviral; in vitro screening; ketone; virus