Identification and structure-activity relationship study of carvacrol derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors

被引：30
|
作者：
Alokam, Reshma [1 ]
Jeankumar, Variam Ullas [1 ]
Sridevi, Jonnalagadda Padma [1 ]
Matikonda, Siddharth Sai [1 ]
Peddi, Santosh [1 ]
Alvala, Mallika [1 ]
Yogeeswari, Perumal [1 ]
Sriram, Dharmarajan [1 ]
机构：
[1] Birla Inst Technol & Sci Pilani, Dept Pharm, Hyderabad 500078, Andhra Pradesh, India
来源：
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2014年 / 29卷 / 04期
关键词：
Carvacrol; chorismate mutase; Mycobacterium; tuberculosis; ESSENTIAL OIL; IN-VITRO; THYMOL; OREGANO;
D O I：
10.3109/14756366.2013.823958
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In the present study, we identified carvacrol, a major phenolic component of oregano oil as a novel small molecule inhibitor of Mycobacterium tuberculosis (MTB) chorismate mutase (CM) enzyme with IC50 of 1.06 +/- 0.4 mu M. Virtual screening of the BITS-Pilani in-house database using the crystal structure of the MTB CM bound transition state intermediate (PDB: 2FP2) as framework identified carvacrol as a potential lead. Further various carvacrol derivatives were evaluated in vitro for their ability to inhibit MTB CM enzyme, whole cell MTB and cytotoxicity as steps toward the derivation of structure-activity relationships (SAR) and lead optimization.
引用
收藏
页码：547 / 554
页数：8
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