Left-Hand Side Exploration of Novel Bacterial Topoisomerase Inhibitors to Improve Selectivity against hERG Binding

ACS Medicinal Chemistry Letters

Volumn 6, Issue 7, 2015, Pages 741-746

  Hameed, Shahul P ^a   Manjrekar, Praveena ^a   Raichurkar, Anandkumar ^a   Shinde, Vikas ^a   Puttur, Jayashree ^a   Shanbhag, Gajanan ^a   Chinnapattu, Murugan ^a   Patil, Vikas ^a   Rudrapatana, Suresh ^a   Sharma, Sreevalli ^a   Naveen Kumar, C N N ^a   Nandishaiah, Radha ^a   Madhavapeddi, Prashanti ^a   Sriram, D ^a,b   Solapure, Suresh ^a   Sambandamurthy, Vasan K ^a  

^a ASTRAZENECA   (United Kingdom)

^b BIRLA INSTITUTE OF TECHNOLOGY AND SCIENCE   (India)

Author keywords

aminopiperidines; DNA gyrase; naphthyridones; NBTIs; Tuberculosis; type II topoisomerases

Indexed keywords

BACTERIAL ENZYME; DNA TOPOISOMERASE (ATP HYDROLYSING); DNA TOPOISOMERASE INHIBITOR; MOXIFLOXACIN; POTASSIUM CHANNEL HERG; TUBERCULOSTATIC AGENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BACTERIAL STRAIN; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG SELECTIVITY; HYDROGEN BOND; IC50; IN VITRO STUDY; IN VIVO STUDY; LIPOPHILICITY; METABOLIC CLEARANCE; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; TUBERCULOSIS; UNBOUND FRACTION;

BACTERIA (MICROORGANISMS); MYCOBACTERIUM TUBERCULOSIS;

EID: 84936870219     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml500531p     Document Type: Article

References (16)

1. World Health Organization. Global tuberculosis report. WHO (2014. http://www.who.int/tb/publications/global-report/en/.
2. Zumla, A.; Raviglione, M.; Hafner, R.; von Reyn, C. F. Tuberculosis N. Engl. J. Med. 2013) 368, 745-755
3. World Health Organization. Multidrug and extensively drug-resistantTB (M/XDR-TB); WHO (2013. http://www.who.int/tb/challenges/mdr/MDR-TB-FactSheet.pdf.
4. Champoux, J. J. DNA topoisomerases: structure, function, and mechanism Annu. Rev. Biochem. 2001) 70, 369-413
5. Corbett, K. D.; Berger, J. M. Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases Annu. Rev. Biophys. Biomol. Struct. 2004, 33, 95-118
6. Mayer, C.; Janin, Y. L. Non-quinolone inhibitors of bacterial type IIA topoisomerases: a feat of bioisosterism Chem. Rev. 2014, 114, 2313-2342
7. Hameed, S. P.; Solapure, S.; Mukherjee, K.; Nandi, V.; Waterson, D.; Shandil, R.; Balganesh, M.; Sambandamurthy, V. K.; Raichurkar, A.; Deshpande, A.; Ghosh, A.; Awasthy, D.; Shanbhag, G.; Sheikh, G.; McMiken, H.; Puttur, P.; Reddy, J.; Werngren, J.; Read, J.; Kumar, M.; Ramaiah, M.; Chinnapattu1, M.; Madhavapeddi, P.; Manjrekar, P.; Basu, R.; Gaonkar, S.; Sharma, S.; Hoffner, S.; Humnabadkar, V.; Subbulakshmi, V.; Panduga, V. Optimization of pyrrolamides as mycobacterial GyrB ATPase inhibitors: Structure-activity relationship and in vivo efficacy in a mouse model of tuberculosis Antimicrob. Agents Chemother. 2013, 58, 6-70
8. Hameed, P. S.; Patil, V.; Solapure, S. M.; Sharma, U.; Madhavapeddi, P.; Raichurkar, A.; Murugan Chinnapattu, M.; Manjrekar, P.; Shanbhag, G.; Puttur, J.; Shinde, V.; Menasinakai, S.; Rudrapatana, S.; Achar, V.; Awasthy, D.; Nandishaiah, R.; Humnabadkar, V.; Ghosh, A.; Narayan, C.; Ramya, V. K.; Kaur, P.; Sharma, S.; Wirngren, J.; Hoffner, H.; Panduga, V.; Naveen Kumar, C. N.; Reddy, J.; Mahesh Kumar, K. N.; Ganguly, S.; Bharath, S.; Mukherjee, K.; Arora, U.; Gaonkar, S.; Coulson, M.; Waterson, D.; Sambandamurthy, V. K.; de Sousa, S. M. Novel N-linked aminopiperidine based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis J. Med. Chem. 2014, 57, 4889-4905
9. Reck, F.; Alm, R.; Brassil, P.; Newman, J.; DeJonge, B.; Eyermann, C. J.; Breault, G.; Breen, J.; Comita-Prevoir, J.; Cronin, M.; Davis, H.; Ehmann, D.; Galullo, V.; Geng, B.; Grebe, T.; Morningstar, M.; Walker, P.; Hayter, B.; Fisher, S. Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II: broad-spectrum antibacterial agents with reduced hERG activity J. Med. Chem. 2011, 54, 7834-7847
10. Reck, F.; Alm, R.; Brassil, P.; Newman, J.; Ciaccio, P.; McNulty, J.; Barthlow, H.; Goteti, K.; Breen, J.; Comita-Prevoir, J.; Cronin, M.; Ehmann, D.; Geng, B.; Godfrey, A.; Fisher, S. Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II with reduced pKa: antibacterial agents with an improved safety profile J. Med. Chem. 2012, 55, 6916-6933
11. Duong, D. A.; Nguyen, T. H.; Nguyen, T. N.; Dai, V. H.; Dang, T. M.; Vo, S. K.; Do, D. A.; Nguyen, V. V.; Nguyen, H. D.; Dinh, N. S.; Farrar, J.; Caws, M. Beijing genotype of Mycobacterium tuberculosis is significantly associated with high-level fluoroquinolone resistance in Vietnam Antimicrob. Agents Chemother. 2009, 53, 4835-4839
12. Ziganshina, L. E.; Titarenko, A. F.; Davies, G. R. Fluoroquinolones for treating tuberculosis (presumed drug-sensitive) Cochrane Database Syst. Rev. 2013, 6, 1-83
13. Bax, B. D.; Chan, P. F.; Eggleston, D. S.; Fosberry, A.; Gentry, D. R.; Gorrec, F.; Giordano, I.; Hann, M. M.; Hennessy, A.; Hibbs, M.; Huang, J.; Jones, E.; Jones, J.; Brown, K. K.; Lewis, C. J.; May, E. W.; Saunders, M. R.; Singh, O.; Spitzfaden, C. E.; Shen, C.; Shillings, A.; Theobald, A. J.; Wohlkonig, A.; Pearson, N. D.; Gwynn, M. N. Type IIA topoisomerase inhibition by a new class of antibacterial agents Nature 2010, 466, 935-940
14. Mitton-Fry, M. J.; Brickner, S. J.; Hamel, J. C.; Brennan, L.; Casavant, J. M.; Chen, M.; Chen, T.; Ding, X.; Driscoll, J.; Hardink, J.; Hoang, T.; Hua, E.; Huband, M. D.; Maloney, M.; Marfat, A.; McCurdy, S. P.; McLeod, D.; Plotkin, M.; Reilly, U.; Robinson, S.; Schafer, J.; Shepard, R. M.; Smith, J. F.; Stone, G. G.; Subramanyam, C.; Yoon, K.; Yuan, W.; Zaniewski, R. P.; Zook, C. Novel quinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV Bioorg. Med. Chem. Lett. 2013, 23, 2955-2961
15. Surivet, J. P.; Zumbrunn, C.; Rueedi, G.; Hubschwerlen, C.; Bur, D.; Bruyère, T.; Locher, H.; Ritz, D.; Keck, W.; Seiler, P.; Kohl, C.; Gauvin, J. C.; Mirre, A.; Kaegi, V.; Dos Santos, M.; Gaertner, M.; Delers, J.; Enderlin-Paput, M.; Boehme, M. Design, synthesis, and characterization of novel tetrahydropyran-based bacterial topoisomerase inhibitors with potent anti-Gram-positive activity J. Med. Chem. 2013, 56, 7396-7415
16. Hameed, P. S.; Raichurkar, A.; Madhavapeddi, P.; Menasinakai, S.; Sharma, S.; Kaur, P.; Nandishaiah, R.; Panduga, V.; Reddy, J.; Sambandamurthy, V. K.; Sriram, D. Benzimidazoles: novel mycobacterial gyrase inhibitors from scaffold morphing ACS Med. Chem. Lett. 2014, 5, 820-825