. 2016 Feb 18;21(2):228.

doi: 10.3390/molecules21020228.

Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus

Shwu-Chen Tsay^{1

2}, Shu-Yu Lin³, Wen-Chieh Huang⁴, Ming-Hua Hsu⁵, Kuo Chu Hwang⁶, Chun-Cheng Lin⁷, Jia-Cherng Horng⁸, I-Chia Chen⁹, Jih Ru Hwu^{10

11}, Fa-Kuen Shieh¹², Pieter Leyssen¹³, Johan Neyts¹⁴

Affiliations

¹ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. tsay.susan@gmail.com.
² Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. tsay.susan@gmail.com.
³ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. kchlsu@mail2000.com.tw.
⁴ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jordanback2001@yahoo.com.tw.
⁵ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. minghua.hsu@gmail.com.
⁶ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. kchwang@mx.nthu.edu.tw.
⁷ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. cclin66@mx.nthu.edu.tw.
⁸ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jchorng@mx.nthu.edu.tw.
⁹ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. icchen@mx.nthu.edu.tw.
¹⁰ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jrhwu@mx.nthu.edu.tw.
¹¹ Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. jrhwu@mx.nthu.edu.tw.
¹² Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. fshieh@ncu.edu.tw.
¹³ Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium. pieter.leyssen@rega.kuleuven.be.
¹⁴ Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium. johan.neyts@rega.kuleuven.be.

PMID: 26901180
PMCID: PMC6273635
DOI: 10.3390/molecules21020228

Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus

Shwu-Chen Tsay et al. Molecules. 2016.

. 2016 Feb 18;21(2):228.

doi: 10.3390/molecules21020228.

Authors

Affiliations

¹ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. tsay.susan@gmail.com.
² Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. tsay.susan@gmail.com.
³ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. kchlsu@mail2000.com.tw.
⁴ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jordanback2001@yahoo.com.tw.
⁵ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. minghua.hsu@gmail.com.
⁶ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. kchwang@mx.nthu.edu.tw.
⁷ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. cclin66@mx.nthu.edu.tw.
⁸ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jchorng@mx.nthu.edu.tw.
⁹ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. icchen@mx.nthu.edu.tw.
¹⁰ Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jrhwu@mx.nthu.edu.tw.
¹¹ Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. jrhwu@mx.nthu.edu.tw.
¹² Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. fshieh@ncu.edu.tw.
¹³ Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium. pieter.leyssen@rega.kuleuven.be.
¹⁴ Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium. johan.neyts@rega.kuleuven.be.

PMID: 26901180
PMCID: PMC6273635
DOI: 10.3390/molecules21020228

Abstract

A series of new conjugated compounds with a -SCH₂- linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC50 values (5.1-8.4 μM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents.

Keywords: coumarin; hepatitis C virus; imidazole; nitrogen heterocycles; structure–activity relationships.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
General structure of targed imidazole–coumarin conjugates.

**Scheme 1**
Synthesis of imidazole–coumarin conjugates.

**Scheme 2**
Synthesis of (1-ribofuranosyl)imidazole–coumarin conjugates.

**Scheme 3**
Synthesis of inosine– and guanosine-coumarin conjugates.

**Figure 2**
Structure of benzimidazole–coumarin conjugates.

See this image and copyright information in PMC

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Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus

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Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus

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