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

Jih Ru Hwu; Mohit Kapoor; Nitesh K Gupta; Shwu-Chen Tsay; Wen-Chieh Huang; Kui-Thong Tan; Yu-Chen Hu; Pieter Lyssen; Johan Neyts

doi:10.1016/j.ejmech.2022.114164

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. Epub 2022 Feb 1.

Authors

Jih Ru Hwu¹, Mohit Kapoor², Nitesh K Gupta², Shwu-Chen Tsay³, Wen-Chieh Huang², Kui-Thong Tan², Yu-Chen Hu⁴, Pieter Lyssen⁵, Johan Neyts⁶

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: jrhwu@mx.nthu.edu.tw.
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: johan.neyts@rega.kuleuven.be.

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.

MeSH terms

Antiviral Agents / pharmacology
Chikungunya Fever*
Chikungunya virus*
Coumarins / pharmacology
Hepacivirus
Humans
Virus Replication

Substances

Antiviral Agents
Coumarins