Investigation of 4-amino-5-alkynylpyrimidine-2(1H)-ones as anti-mycobacterial agents

被引：2

作者：

Garg, Gaurav ^{[1
]}

Pande, Milind ^{[2
]}

Agrawal, Ambika ^{[3
]}

Li, Jie ^{[4
]}

Kumar, Rakesh ^{[3
]}

机构：

[1] Mangalayatan Univ, Dept Pharm, Aligarh, UP, India

[2] Peoples Univ, Sch Pharm, Bhopal, MP, India

[3] Univ Alberta, Fac Med & Dent, Dept Lab Med & Pathol, HMRC 728, Edmonton, AB T6G 2S2, Canada

[4] Univ Alberta, Dept Surg, Edmonton, AB T6G 2S2, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 08期

基金：

加拿大健康研究院;

关键词：

Tuberculosis; Heterocycles; Pyrimidines; Anti-mycobacterial agent; DNA-POLYMERASE-III; IN-VITRO; MYCOBACTERIUM-TUBERCULOSIS; REPLICATION; PREVENTION;

D O I：

10.1016/j.bmc.2016.03.003

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 vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1H)-ones were investigated. 4-Amino-5-heptynylpyrimidine-2(1H)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2 (1H)-one (7) displayed potent in vitro activity against Mycobacterium bovis and Mycobacterium tuberculosis. Compounds 3 and 7 were also assessed for their in vivo activity in BALB/c mice infected with M. tuberculosis (H37Ra). Both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks. Importantly, compounds 3 and 7 interacted synergistically with the front-line anti-tuberculosis drug isoniazid in vitro and in vivo. These results suggest that this class of compounds has strong anti-mycobacterial potential. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1771 / 1777

页数：7

共 22 条

[1]

Campos-Outcalt D, 2003, J FAM PRACTICE, V52, P792

[2] Fractographic analysis of fractured dental implant components [J].

Chang, Chih-Ling ;

Lu, Hsien-Kun ;

Ou, Keng-Liang ;

Su, Peng-Yu ;

Chen, Chung-Ming .

JOURNAL OF DENTAL SCIENCES, 2013, 8 (01) :8-14

[3] The sonogashira reaction:: A booming methodology in synthetic organic chemistry [J].

Chinchilla, Rafael ;

Najera, Carmen .

CHEMICAL REVIEWS, 2007, 107 (03) :874-922

[4] Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence [J].

Cole, ST ;

Brosch, R ;

Parkhill, J ;

Garnier, T ;

Churcher, C ;

Harris, D ;

Gordon, SV ;

Eiglmeier, K ;

Gas, S ;

Barry, CE ;

Tekaia, F ;

Badcock, K ;

Basham, D ;

Brown, D ;

Chillingworth, T ;

Connor, R ;

Davies, R ;

Devlin, K ;

Feltwell, T ;

Gentles, S ;

Hamlin, N ;

Holroyd, S ;

Hornby, T ;

Jagels, K ;

Krogh, A ;

McLean, J ;

Moule, S ;

Murphy, L ;

Oliver, K ;

Osborne, J ;

Quail, MA ;

Rajandream, MA ;

Rogers, J ;

Rutter, S ;

Seeger, K ;

Skelton, J ;

Squares, R ;

Squares, S ;

Sulston, JE ;

Taylor, K ;

Whitehead, S ;

Barrell, BG .

NATURE, 1998, 393 (6685) :537-+

[5] Genomic Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis During Transcontinental Spread [J].

Coscolla, Mireia ;

Barry, Pennan M. ;

Oeltmann, John E. ;

Koshinsky, Heather ;

Shaw, Tambi ;

Cilnis, Martin ;

Posey, Jamie ;

Rose, Jordan ;

Weber, Terry ;

Fofanov, Viacheslav Y. ;

Gagneux, Sebastien ;

Kato-Maeda, Midori ;

Metcalfe, John Z. .

JOURNAL OF INFECTIOUS DISEASES, 2015, 212 (02) :302-310

[6] Human Immunodeficiency Virus-Associated Tuberculosis Update on Prevention and Treatment [J].

Dierberg, Kerry L. ;

Chaisson, Richard E. .

CLINICS IN CHEST MEDICINE, 2013, 34 (02) :217-+

[7] Multidrug-Resistant Tuberculosis in Europe, 2010-2011 [J].

Guenther, Gunar ;

van Leth, Frank ;

Alexandru, Sofia ;

Altet, Neus ;

Avsar, Korkut ;

Bang, Didi ;

Barbuta, Raisa ;

Bothamley, Graham ;

Ciobanu, Ana ;

Crudu, Valeriu ;

Danilovits, Manfred ;

Dedicoat, Martin ;

Duarte, Raquel ;

Gualano, Gina ;

Kunst, Heinke ;

de Lange, Wiel ;

Leimane, Vaira ;

Magis-Escurra, Cecile ;

McLaughlin, Anne-Marie ;

Muylle, Inge ;

Polcova, Veronika ;

Pontalli, Emanuele ;

Popa, Christina ;

Rumetshofer, Rudolf ;

Skrahina, Alena ;

Solodovnikova, Varvara ;

Spinu, Victor ;

Tiberi, Simon ;

Viiklepp, Piret ;

Lange, Christoph .

EMERGING INFECTIOUS DISEASES, 2015, 21 (03) :409-416

[8] INVITRO SYNERGISTIC ACTIVITY BETWEEN ETHAMBUTOL AND FLUORINATED QUINOLONES AGAINST MYCOBACTERIUM-AVIUM COMPLEX [J].

HOFFNER, SE ;

KRATZ, M ;

OLSSONLILJEQUIST, B ;

SVENSON, SB ;

KALLENIUS, G .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1989, 24 (03) :317-324

[9] In Silico Screening for Novel Inhibitors of DNA Polymerase III Alpha Subunit of Mycobacterium tuberculosis (MtbDnaE2, H37Rv) (vol 10, e0119760, 2015) [J].

Jadaun, Alka ;

Sudhakar, Raja D. ;

Subbarao, N. ;

Dixit, Aparna .

PLOS ONE, 2015, 10 (05)

[10] Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides [J].

Johar, M ;

Manning, T ;

Kunimoto, DY ;

Kumar, R .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (24) :6663-6671

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