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2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and Mycobacterium tuberculosis: Structure-Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion Characterization.

Murugesan D, Ray PC, Bayliss T, Prosser GA, Harrison JR, Green K, Soares de Melo C, Feng TS, Street LJ, Chibale K, Warner DF, Mizrahi V, Epemolu O, Scullion P, Ellis L, Riley J, Shishikura Y, Ferguson L, Osuna-Cabello M, Read KD, Green SR, Lamprecht DA, Finin PM, Steyn AJC, Ioerger TR, Sacchettini J, Rhee KY, Arora K, Barry CE 3rd, Wyatt PG, Boshoff HIM.

ACS Infect Dis. 2018 Jun 8;4(6):954-969. doi: 10.1021/acsinfecdis.7b00275. Epub 2018 Mar 26.


Small Molecules Targeting Mycobacterium tuberculosis Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity.

Harbut MB, Yang B, Liu R, Yano T, Vilchèze C, Cheng B, Lockner J, Guo H, Yu C, Franzblau SG, Petrassi HM, Jacobs WR Jr, Rubin H, Chatterjee AK, Wang F.

Angew Chem Int Ed Engl. 2018 Mar 19;57(13):3478-3482. doi: 10.1002/anie.201800260. Epub 2018 Feb 22.


Type-II NADH Dehydrogenase (NDH-2): a promising therapeutic target for antitubercular and antibacterial drug discovery.

Sellamuthu S, Singh M, Kumar A, Singh SK.

Expert Opin Ther Targets. 2017 Jun;21(6):559-570. doi: 10.1080/14728222.2017.1327577. Epub 2017 May 15. Review.


Roles of the two type II NADH dehydrogenases in the survival of Mycobacterium tuberculosis in vitro.

Awasthy D, Ambady A, Narayana A, Morayya S, Sharma U.

Gene. 2014 Oct 15;550(1):110-6. doi: 10.1016/j.gene.2014.08.024. Epub 2014 Aug 13.


Plasticity of Mycobacterium tuberculosis NADH dehydrogenases and their role in virulence.

Vilchèze C, Weinrick B, Leung LW, Jacobs WR Jr.

Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1599-1604. doi: 10.1073/pnas.1721545115. Epub 2018 Jan 30.


The global motion affecting electron transfer in Plasmodium falciparum type II NADH dehydrogenases: a novel non-competitive mechanism for quinoline ketone derivative inhibitors.

Xie T, Wu Z, Gu J, Guo R, Yan X, Duan H, Liu X, Liu W, Liang L, Wan H, Luo Y, Tang D, Shi H, Hu J.

Phys Chem Chem Phys. 2019 Aug 21;21(33):18105-18118. doi: 10.1039/c9cp02645b.


Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation.

Heikal A, Nakatani Y, Dunn E, Weimar MR, Day CL, Baker EN, Lott JS, Sazanov LA, Cook GM.

Mol Microbiol. 2014 Mar;91(5):950-64. doi: 10.1111/mmi.12507. Epub 2014 Jan 21.


Identification of new inhibitors for alternative NADH dehydrogenase (NDH-II).

Mogi T, Matsushita K, Murase Y, Kawahara K, Miyoshi H, Ui H, Shiomi K, Omura S, Kita K.

FEMS Microbiol Lett. 2009 Feb;291(2):157-61. doi: 10.1111/j.1574-6968.2008.01451.x. Epub 2008 Dec 5.


Type 2 NADH Dehydrogenase Is the Only Point of Entry for Electrons into the Streptococcus agalactiae Respiratory Chain and Is a Potential Drug Target.

Lencina AM, Franza T, Sullivan MJ, Ulett GC, Ipe DS, Gaudu P, Gennis RB, Schurig-Briccio LA.

MBio. 2018 Jul 3;9(4). pii: e01034-18. doi: 10.1128/mBio.01034-18.


Mycobacterium tuberculosis type II NADH-menaquinone oxidoreductase catalyzes electron transfer through a two-site ping-pong mechanism and has two quinone-binding sites.

Yano T, Rahimian M, Aneja KK, Schechter NM, Rubin H, Scott CP.

Biochemistry. 2014 Feb 25;53(7):1179-90. doi: 10.1021/bi4013897. Epub 2014 Feb 11.


Activation of type II NADH dehydrogenase by quinolinequinones mediates antitubercular cell death.

Heikal A, Hards K, Cheung CY, Menorca A, Timmer MS, Stocker BL, Cook GM.

J Antimicrob Chemother. 2016 Oct;71(10):2840-7. doi: 10.1093/jac/dkw244. Epub 2016 Jun 30.


'Tethering' fragment-based drug discovery to identify inhibitors of the essential respiratory membrane protein type II NADH dehydrogenase.

Heikal A, Nakatani Y, Jiao W, Wilson C, Rennison D, Weimar MR, Parker EJ, Brimble MA, Cook GM.

Bioorg Med Chem Lett. 2018 Jul 15;28(13):2239-2243. doi: 10.1016/j.bmcl.2018.05.048. Epub 2018 May 26.


Identification and optimization of a new series of anti-tubercular quinazolinones.

Couturier C, Lair C, Pellet A, Upton A, Kaneko T, Perron C, Cogo E, Menegotto J, Bauer A, Scheiper B, Lagrange S, Bacqué E.

Bioorg Med Chem Lett. 2016 Nov 1;26(21):5290-5299. doi: 10.1016/j.bmcl.2016.09.043. Epub 2016 Sep 16.


Synthesis, crystal structure and biological evaluation of substituted quinazolinone benzoates as novel antituberculosis agents targeting acetohydroxyacid synthase.

Lu W, Baig IA, Sun HJ, Cui CJ, Guo R, Jung IP, Wang D, Dong M, Yoon MY, Wang JG.

Eur J Med Chem. 2015 Apr 13;94:298-305. doi: 10.1016/j.ejmech.2015.03.014. Epub 2015 Mar 7.


Characterization of the type 2 NADH:menaquinone oxidoreductases from Staphylococcus aureus and the bactericidal action of phenothiazines.

Schurig-Briccio LA, Yano T, Rubin H, Gennis RB.

Biochim Biophys Acta. 2014 Jul;1837(7):954-63. doi: 10.1016/j.bbabio.2014.03.017. Epub 2014 Apr 5.


The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis.

Korkegian A, O'Malley T, Xia Y, Zhou Y, Carter DS, Sunde B, Flint L, Thompson D, Ioerger TR, Sacchettini J, Alley MRK, Parish T.

Tuberculosis (Edinb). 2018 Jan;108:96-98. doi: 10.1016/ Epub 2017 Nov 7.


Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with 'inverted' binding mode.

Darras FH, Wehle S, Huang G, Sotriffer CA, Decker M.

Bioorg Med Chem. 2014 Sep 1;22(17):4867-81. doi: 10.1016/j.bmc.2014.06.045. Epub 2014 Jul 1.


Quinolinyl Pyrimidines: Potent Inhibitors of NDH-2 as a Novel Class of Anti-TB Agents.

Shirude PS, Paul B, Roy Choudhury N, Kedari C, Bandodkar B, Ugarkar BG.

ACS Med Chem Lett. 2012 Aug 13;3(9):736-40. doi: 10.1021/ml300134b. eCollection 2012 Sep 13.


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