2-Aminothiazole derivatives as antimycobacterial agents: Synthesis, characterization, in vitro and in silico studies

被引：45

作者：

Makam, Parameshwar ^{[1
]}

Kannan, Tharanikkarasu ^{[1
]}

机构：

[1] Pondicherry Univ, Dept Chem, Pondicherry 605014, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 87卷

关键词：

Mycobacterium tuberculosis; Tuberculosis; 2-Aminothiazole; Drug like molecule; beta-Ketoacyl-ACP Synthase; Docking studies; MYCOBACTERIUM-TUBERCULOSIS; CRYSTAL-STRUCTURES; DRUG DISCOVERY; DESIGN; INHIBITORS; MOLECULE;

D O I：

10.1016/j.ejmech.2014.09.086

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-aminothiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed and synthesized using Hantzsch thiazole synthesis. These compounds were evaluated for their inhibitory potential against Mycobacterium tuberculosis (Mtb), H(37)Rv. The compound. 7n showed high antimycobacterial activity with WC value of 6.25 mu M and the succeeding compounds, 7b, 7e and 7f also exhibited antimycobacterial activity with MIC value of 12.50 mu M. Docking studies of these molecules with beta-Ketoacyl-ACP Synthase (KasA) protein of Mtb have been carried out to understand the mechanism of antimycobacterial action. The compound, 7n showed good interaction with KasA protein with the K-i value of 0.44 mu M. (c) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：643 / 656

页数：14

共 63 条

[1] Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH [J].

Al-Balas, Qosay ;

Anthony, Nahoum G. ;

Al-Jaidi, Bilal ;

Alnimr, Amani ;

Abbott, Grainne ;

Brown, Alistair K. ;

Taylor, Rebecca C. ;

Besra, Gurdyal S. ;

McHugh, Timothy D. ;

Gillespie, Stephen H. ;

Johnston, Blair F. ;

Mackay, Simon P. ;

Coxon, Geoffrey D. .

PLOS ONE, 2009, 4 (05)

[2] High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv [J].

Ananthan, Subramaniam ;

Faaleolea, Ellen R. ;

Goldman, Robert C. ;

Hobrath, Judith V. ;

Kwong, Cecil D. ;

Laughon, Barbara E. ;

Maddry, Joseph A. ;

Mehta, Alka ;

Rasmussen, Lynn ;

Reynolds, Robert C. ;

Secrist, John A., III ;

Shindo, Nice ;

Showe, Dustin N. ;

Sosa, Melinda I. ;

Suling, William J. ;

White, E. Lucile .

TUBERCULOSIS, 2009, 89 (05) :334-353

[3]

[Anonymous], ASIAN J RES CHEM

[4] Dasatinib: A potent SRC inhibitor in clinical development for the treatment of solid tumors [J].

Araujo, John ;

Logothetis, Christopher .

CANCER TREATMENT REVIEWS, 2010, 36 (06) :492-500

[5] The influence of lipophilicity in drug discovery and design [J].

Arnott, John A. ;

Planey, Sonia Lobo .

EXPERT OPINION ON DRUG DISCOVERY, 2012, 7 (10) :863-875

[6] Rv1218c, an ABC Transporter of Mycobacterium tuberculosis with Implications in Drug Discovery [J].

Balganesh, Meenakshi ;

Kuruppath, Sanjana ;

Marcel, Nimi ;

Sharma, Sreevalli ;

Nair, Anju ;

Sharma, Umender .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (12) :5167-5172

[7] Small molecule conformational preferences derived from crystal structure data. A medicinal chemistry focused analysis [J].

Brameld, Ken A. ;

Kuhn, Bernd ;

Reuter, Deborah C. ;

Stahl, Martin .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2008, 48 (01) :1-24

[8] 2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97) [J].

Bursavich, Matthew G. ;

Parker, Daniel P. ;

Willardsen, J. Adam ;

Gao, Zhong-Hua ;

Davis, Thaylon ;

Ostanin, Kirill ;

Robinson, Rosann ;

Peterson, Ashley ;

Cimbora, Daniel M. ;

Zhu, Ju-Fen ;

Richards, Burt .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (05) :1677-1679

[9] Novel Orally Active Antimalarial Thiazoles [J].

Cabrera, Diego Gonzalez ;

Douelle, Frederic ;

Feng, Tzu-Shean ;

Nchinda, Aloysius T. ;

Younis, Yassir ;

White, Karen L. ;

Wu, Quoc ;

Ryan, Eileen ;

Burrows, Jeremy N. ;

Waterson, David ;

Witty, Michael J. ;

Wittlin, Sergio ;

Charman, Susan A. ;

Chibale, Kelly .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (21) :7713-7719

[10] Design and synthesis of sulfonyl-substituted 4,5-diarylthiazoles as selective cyclooxygenase-2 inhibitors [J].

Carter, JS ;

Rogier, DJ ;

Graneto, MJ ;

Seibert, K ;

Koboldt, CM ;

Zhang, Y ;

Talley, JJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (08) :1167-1170

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