Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles
Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimi...
Saved in:
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Published: |
Wiley
2017
|
Subjects: | |
Online Access: | http://eprints.um.edu.my/20276/ https://doi.org/10.1111/cbdd.13072 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Universiti Malaya |
id |
my.um.eprints.20276 |
---|---|
record_format |
eprints |
spelling |
my.um.eprints.202762019-08-26T02:22:59Z http://eprints.um.edu.my/20276/ Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles Yeong, Keng Yoon Tan, Soo Choon Mai, Chun-Wai Leong, Chee-Onn Chung, Felicia Fei-Lei Lee, Yean Kee Chee, Chin Fei Abd Rahman, Noorsaadah Q Science (General) QD Chemistry R Medicine Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results. Wiley 2017 Article PeerReviewed Yeong, Keng Yoon and Tan, Soo Choon and Mai, Chun-Wai and Leong, Chee-Onn and Chung, Felicia Fei-Lei and Lee, Yean Kee and Chee, Chin Fei and Abd Rahman, Noorsaadah (2017) Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles. Chemical Biology & Drug Design, 91 (1). pp. 213-219. ISSN 1747-0277 https://doi.org/10.1111/cbdd.13072 doi:10.1111/cbdd.13072 |
institution |
Universiti Malaya |
building |
UM Library |
collection |
Institutional Repository |
continent |
Asia |
country |
Malaysia |
content_provider |
Universiti Malaya |
content_source |
UM Research Repository |
url_provider |
http://eprints.um.edu.my/ |
topic |
Q Science (General) QD Chemistry R Medicine |
spellingShingle |
Q Science (General) QD Chemistry R Medicine Yeong, Keng Yoon Tan, Soo Choon Mai, Chun-Wai Leong, Chee-Onn Chung, Felicia Fei-Lei Lee, Yean Kee Chee, Chin Fei Abd Rahman, Noorsaadah Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles |
description |
Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results. |
format |
Article |
author |
Yeong, Keng Yoon Tan, Soo Choon Mai, Chun-Wai Leong, Chee-Onn Chung, Felicia Fei-Lei Lee, Yean Kee Chee, Chin Fei Abd Rahman, Noorsaadah |
author_facet |
Yeong, Keng Yoon Tan, Soo Choon Mai, Chun-Wai Leong, Chee-Onn Chung, Felicia Fei-Lei Lee, Yean Kee Chee, Chin Fei Abd Rahman, Noorsaadah |
author_sort |
Yeong, Keng Yoon |
title |
Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles |
title_short |
Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles |
title_full |
Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles |
title_fullStr |
Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles |
title_full_unstemmed |
Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles |
title_sort |
contrasting sirtuin and poly(adp-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles |
publisher |
Wiley |
publishDate |
2017 |
url |
http://eprints.um.edu.my/20276/ https://doi.org/10.1111/cbdd.13072 |
_version_ |
1643691232068632576 |