Sammanfattning

A combination of a literature survey, structure-based virtual screening and synthesis of a small library was performed to identify hits to the potential antimycobacterial drug target, glutamine synthetase. The best inhibitor identified from the literature survey was (2S, 5R)-2,6-diamino-5-hydroxyhexanoic acid ( 4, IC(50) of 610 +/- 15 mu M). In the virtual screening 46,400 compounds were docked and subjected to a pharmacophore search. Of these compounds, 29 were purchased and tested in a biological assay, allowing three novel inhibitors containing an aromatic scaffold to be identified. Based on one of the hits from the virtual screening a small library of 15 analogues was synthesized producing four compounds that inhibited glutamine synthetase. (C) 2008 Elsevier Ltd. All rights reserved.

Nyckelord

virtual screening; glutamine synthetase; gamma-glutamyl : ammonia ligase

Publicerad i

Bioorganic and Medicinal Chemistry
2008, Volym: 16, nummer: 10, sidor: 5501-5513

SLU författare

• Mowbray, Sherry

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

Globala målen

SDG3 Säkerställa hälsosamma liv och främja välbefinnande för alla i alla åldrar


UKÄ forskningsämne

Livsmedelsvetenskap


Publikationens identifierare

DOI: https://doi.org/10.1016/j.bmc.2008.04.015

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/30887