Inhibitors of the Salicylate Synthase (MbtI) from Mycobacterium tuberculosis Discovered by High-Throughput Screening

被引：48

作者：

Vasan, Mahalakshmi ^{[1
]}

Neres, Joao ^{[1
]}

Williams, Jessica ^{[1
]}

Wilson, Daniel J. ^{[1
]}

Teitelbaum, Aaron M. ^{[2
]}

Remmel, Rory P. ^{[2
]}

Aldrich, Courtney C. ^{[1
]}

机构：

[1] Univ Minnesota, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA

来源：

CHEMMEDCHEM | 2010年 / 5卷 / 12期

关键词：

high-throughput screening; mycobactins; salicylate synthase; siderophores; tuberculosis; CHORISMATE-UTILIZING ENZYMES; PHOSPHATASE 1B PTP1B; IRON ACQUISITION; 4-AMINO-4-DEOXYCHORISMATE SYNTHASE; ISOCHORISMATE SYNTHASE; SIDEROPHORE MYCOBACTIN; ISOTHIAZOLONE BIOCIDES; REDOX REGULATION; IDENTIFICATION; BIOSYNTHESIS;

D O I：

10.1002/cmdc.201000275

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A simple steady-state kinetic high-throughput assay was developed for the salicylate synthase MbtI from Mycobacterium tuberculosis, which catalyzes the first committed step of mycobactin biosynthesis. The mycobactins are small-molecule iron chelators produced by M. tuberculosis, and their biosynthesis has been identified as a promising target for the development of new antitubercular agents. The assay was miniaturized to a 384-well plate format and high-throughput screening was performed at the National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases (NSRB). Three classes of compounds were identified comprising the benzisothiazolones (class I), diarylsulfones (class II), and benzimidazole-2-thiones (class III). Each of these compound series was further pursued to investigate their biochemical mechanism and structure-activity relationships. Benzimidazole-2-thione 4 emerged as the most promising inhibitor owing to its potent reversible inhibition.

引用

页码：2079 / 2087

页数：9

共 50 条

[21] Multifunctional chemical inhibitors of the florigen activation complex discovered by structure-based high-throughput screening [J].

Taoka, Ken-Ichiro ;

Kawahara, Ikumi ;

Shinya, Shoko ;

Harada, Ken-Ichi ;

Yamashita, Eiki ;

Shimatani, Zenpei ;

Furuita, Kyoko ;

Muranaka, Tomoaki ;

Oyama, Tokitaka ;

Terada, Rie ;

Nakagawa, Atsushi ;

Fujiwara, Toshimichi ;

Tsuji, Hiroyuki ;

Kojima, Chojiro .

PLANT JOURNAL, 2022, 112 (06) :1337-1349

[22] Machine Learning-Based High-Throughput Screening, Molecular Modeling and Quantum Chemical Analysis to Investigate Mycobacterium tuberculosis MetRS Inhibitors [J].

Maharjan, Rajesh ;

Gyawali, Kalpana ;

Acharya, Arjun ;

Khanal, Madan ;

Khanal, Kamal ;

Kshetri, Mohan Bahadur ;

Ghimire, Madhav Prasad ;

Lamichhane, Tika Ram .

CHEMISTRYOPEN, 2025,

[23] A high-throughput screening for inhibitors of riboflavin synthase identifies novel antimicrobial compounds to treat brucellosis [J].

Serer, Maria Ines ;

del Carmen Carrica, Mariela ;

Trappe, Jorg ;

Romero, Sandra Lopez ;

Bonomi, Hernan Ruy ;

Klinke, Sebastian ;

Cerutti, Maria Laura ;

Alberto Goldbaum, Fernando .

FEBS JOURNAL, 2019, 286 (13) :2522-2535

[24] New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents [J].

Chiarelli, Laurent R. ;

Mori, Matteo ;

Beretta, Giangiacomo ;

Gelain, Arianna ;

Pini, Elena ;

Sammartino, Jose Camilla ;

Stelitano, Giovanni ;

Barlocco, Daniela ;

Costantino, Luca ;

Lapillo, Margherita ;

Poli, Giulio ;

Caligiuri, Isabella ;

Rizzolio, Flavio ;

Bellinzoni, Marco ;

Tuccinardi, Tiziano ;

Villa, Stefania ;

Meneghetti, Fiorella .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2019, 34 (01) :823-828

[25] High-Throughput Screening for Terpene-Synthase-Cyclization Activity and Directed Evolution of a Terpene Synthase [J].

Lauchli, Ryan ;

Rabe, Kersten S. ;

Kalbarczyk, Karolina Z. ;

Tata, Amulya ;

Heel, Thomas ;

Kitto, Rebekah Z. ;

Arnold, Frances H. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2013, 52 (21) :5571-5574

[26] High-throughput screening of compounds library to identify novel inhibitors against latent Mycobacterium tuberculosis using streptomycin-dependent Mycobacterium tuberculosis 18b strain as a model [J].

Sharma, Smriti ;

Bhat, Rahul ;

Singh, Rohit ;

Sharma, Sumit ;

Wazir, Priya ;

Singh, Parvinder Pal ;

Vishwakarma, Ram A. ;

Khan, Inshad Ali .

TUBERCULOSIS, 2020, 124

[27] High-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU [J].

Rani, Chitra ;

Mehra, Rukmankesh ;

Sharma, Rashmi ;

Chib, Reena ;

Wazir, Priya ;

Nargotra, Amit ;

Khan, Inshad Ali .

TUBERCULOSIS, 2015, 95 (06) :664-677

[28] High-throughput screening for human collagenase 1 inhibitors [J].

Ye, QZ ;

Nan, FJ ;

Hu, LY ;

Qian, Z ;

Qian, J .

ACTA PHARMACOLOGICA SINICA, 2000, 21 (11) :1021-1026

[29] Structural basis for specific inhibition of salicylate synthase from Mycobacterium abscessus [J].

Mori, Matteo ;

Cocorullo, Mario ;

Tresoldi, Andrea ;

Cazzaniga, Giulia ;

Gelain, Arianna ;

Stelitano, Giovanni ;

Chiarelli, Laurent R. ;

Tomaiuolo, Martina ;

Delre, Pietro ;

Mangiatordi, Giuseppe F. ;

Garofalo, Mariangela ;

Cassetta, Alberto ;

Covaceuszach, Sonia ;

Villa, Stefania ;

Meneghetti, Fiorella .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2024, 265

[30] Discovery of novel inhibitors targeting the Mycobacterium tuberculosis O-acetylserine sulfhydrylase (CysK1) using virtual high-throughput screening [J].

Kumar, Variam Ullas Jean ;

Poyraz, Omer ;

Saxena, Shalini ;

Schnell, Robert ;

Yogeeswari, Perumal ;

Schneider, Gunter ;

Sriram, Dharmarajan .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (05) :1182-1186

← 1 2 3 4 5 →