Synthesis and antiviral activities of quinazolinamine-coumarin conjugates toward chikungunya and hepatitis C viruses

  • Eur J Med Chem. 2022 Mar 15:232:114164. doi: 10.1016/j.ejmech.2022.114164.
Jih Ru Hwu  1 ,  Mohit Kapoor  2 ,  Nitesh K Gupta  2 ,  Shwu-Chen Tsay  3 ,  Wen-Chieh Huang  2 ,  Kui-Thong Tan  2 ,  Yu-Chen Hu  4 ,  Pieter Lyssen  5 ,  Johan Neyts  6
Affiliations
  • 1. Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, 30013, Taiwan; Department of Chemistry, National Central University, Jhongli City, 32001, Taiwan. Electronic address: [email protected].
  • 2. Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, 30013, Taiwan.
  • 3. Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, 30013, Taiwan; Department of Chemistry, National Central University, Jhongli City, 32001, Taiwan.
  • 4. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.
  • 5. Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
  • 6. Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium. Electronic address: [email protected].
PMID: 35176562 DOI: 10.1016/j.ejmech.2022.114164
Abstract

Development of new drugs with broad-spectrum to combat RNA viruses would be beneficial to mankind but faces a great challenge. We designed and efficiently synthesized a series of quinazolin-4-amine-SCH2-coumarin conjugated compounds. Our data of the virus-cell-based assay show five new conjugates inhibit chikungunya virus with EC50 values as potent as 1.96 μM and two conjugates inhibit hepatitis C virus with EC50 values as low as 16.6 μM. These conjugates possess a xylene substituent at the C-4 amino group of quinazoline and a t-butyl substituent at the C-6' position of coumarin.

Keywords
Broad-spectrum; Chikungunya virus; Coumarin; Hepatitis C virus; Quinazolin-4-amine; Structure–activity relationship.