Structure-activity relationships of spectinamide antituberculosis agents: A dissection of ribosomal inhibition and native efflux avoidance contributions

ACS Infectious Diseases

Volumn 3, Issue 1, 2017, Pages 72-88

  Liu, Jiuyu ^a   Bruhn, David F ^a   Lee, Robin B ^a   Zheng, Zhong ^a   Janusic, Tanja ^b   Scherbakov, Dimitri ^b   Scherman, Michael S ^c   Boshoff, Helena I ^d   Das, Sourav ^a   Rakesh, ^a   Waidyarachchi, Samanthi L ^a   Brewer, Tiffany A ^a,e   Gracia, Begoña ^f   Yang, Lei ^a   Bollinger, John ^a   Robertson, Gregory T ^c   Meibohm, Bernd ^e   Lenaerts, Anne J ^c   Ainsa, Jose ^f   Böttger, Erik C ^b   Lee, Richard E ^a   more..

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b UNIVERSITY OF ZURICH   (Switzerland)

^c Department of Environmental and Radiological Health Sciences   (United States)

^d NATIONAL INSTITUTES OF HEALTH   (United States)

^e UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^f UNIVERSITY OF ZARAGOZA   (Spain)

Author keywords

Antituberculosis; Efficacy; Efflux pump; Spectinamide; Spectinomycin; Structure activity relationship

Indexed keywords

3' DIHYDRO 3' (4 METHYLPYRIDIN 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' (BENZO[D]THIAZOL 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBORIDE; 3' DIHYDRO 3' DEOXY (PYRIDIN 2 YL)AMINOCARBONYLAMINO SPECTINOMYCIN DIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 3' (1H IMIDAZOL 1 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (1H IMIDAZOL 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 3' (1H IMIDAZOL 4 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (1H INDOL 2 YL)ACETYLAMINO SPECTINOMYCIN; 3' DIHYDRO 3' DEOXY 3' (1H PYRAZOL 1 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBRORIDE; 3' DIHYDRO 3' DEOXY 3' (2 AMINOTHIAZOL 4 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (3 METHYLPYRIDIN 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (5 METHYLPYRIDIN 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (BENZO[D]OXAZOL 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBORIDE; 3' DIHYDRO 3' DEOXY 3' (PYRAZIN 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (PYRIDAZIN 3 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (PYRIDIN 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' (PYRIDIN 2 YL)PROPANOYLAMINO SPECTINOMYCIN TRIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 3' (PYRIDIN 3 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 3' (PYRIDIN 4 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 3' (PYRIMIDIN 4 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 3' (THIAZOL 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' -(1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBORIDE; 3' DIHYDRO 3' DEOXY 3' BENZYLSULFONYLAMINO SPECTINOMYCIN DIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' PHENYLAMINOCARBONYLAMINO SPECTINOMYCIN TRIHYDROBROMIDE; 3' DIHYDRO 3' DEOXY 3' PHENYLOXYCARBONYLAMINO SPECTINOMYCIN DIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 3' PYRIDIN 2 CARBOXYLICAMINO SPECTINOMYCIN TRIHYDROCHLORIDE; 3' DIHYDRO 3' DEOXY 4 2 PHENYLETHYLAMINO SPECTINOMYCIN TRIHYDROCHLORIDE; 3' DIHYDRO3' (1H BENZO[D]IMIDAZOL 2 YL)ACETYLAMINO SPECTINOMYCIN TRIHYDROBORIDE; SPECTINAMIDE; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG; SPECTINOMYCIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERIAL LOAD; COMPLEX FORMATION; CONTROLLED STUDY; DEFENSE MECHANISM; DRUG DOSE ESCALATION; DRUG EFFICACY; MINIMUM INHIBITORY CONCENTRATION; MOLECULAR DYNAMICS; MOUSE; MULTIDRUG RESISTANCE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; TUBERCULOSIS; VERO CELL LINE; WILD TYPE; ANALOGS AND DERIVATIVES; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; MOLECULAR MODEL; RIBOSOME;

ANTITUBERCULAR AGENTS; DRUG DISCOVERY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; RIBOSOMES; SPECTINOMYCIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 85017581247     PISSN: None     EISSN: 23738227     Source Type: Journal    
DOI: 10.1021/acsinfecdis.6b00158     Document Type: Article

References (30)

1. Hoagland, D., Zhao, Y., and Lee, R. E. (2016) Advances in Drug Discovery and Development for Pediatric Tuberculosis. Mini-Rev. Med. Chem. 16 (6), 481-497.
2. Hoagland, D. T., Liu, J., Lee, R. B., and Lee, R. E. (2016) New agents for the treatment of drug-resistant Mycobacterium tuberculosis. Adv. Drug Delivery Rev. 102, 55-72.
3. Mdluli, K., Kaneko, T., and Upton, A., The tuberculosis drug discovery and development pipeline and emerging drug targets. Cold Spring Harbor Perspect. Med. 2015, 5 (6), a02115410.1101/cshperspect. a021154.
4. Lee, R. E., Hurdle, J. G., Liu, J., Bruhn, D. F., Matt, T., Scherman, M. S., Vaddady, P. K., Zheng, Z., Qi, J., Akbergenov, R., Das, S., Madhura, D. B., Rathi, C., Trivedi, A., Villellas, C., Lee, R. B., Rakesh, Waidyarachchi, S. L., Sun, D., McNeil, M. R., Ainsa, J. A., Boshoff, H. I., Gonzalez-Juarrero, M., Meibohm, B., Bottger, E. C., and Lenaerts, A. J. (2014) Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux. Nat. Med. 20 (2), 152-158.
5. Carter, A. P., Clemons, W. M., Brodersen, D. E., Morgan-Warren, R. J., Wimberly, B. T., and Ramakrishnan, V. (2000) Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407 (6802), 340-348.
6. Borovinskaya, M. A., Shoji, S., Holton, J. M., Fredrick, K., and Cate, J. H. (2007) A steric block in translation caused by the antibiotic spectinomycin. ACS Chem. Biol. 2 (8), 545-552.
7. Balganesh, M., Dinesh, N., Sharma, S., Kuruppath, S., Nair, A. V., and Sharma, U. (2012) Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates. Antimicrob. Agents Chemother. 56 (5), 2643-2651.
8. Novak, E., Schlagel, C. A., LeZotte, L. A., and Pfeifer, R. T. (1974) The tolerance of high dose intravenous spectinomycin therapy in man. J. Clin. Pharmacol. 14 (8), 442-447.
9. Hoeksema, H., Argoudelis, A. D., and Wiley, P. F. (1962) Chemistry of Actinospectacin. II. The Structure of Actinospectacin. J. Am. Chem. Soc. 84 (16), 3212-3213.
10. Foley, L., Lin, J. T., and Weigele, M. (1978) Spectinomycin chemistry. III.9-EPI-4(R)-dihydrospectinomycin and 9-epi-spectinomycin. J. Antibiot. 31 (10), 985-990.
11. Foley, L., Lin, J. T., and Weigele, M. (1978) Spectinomycin chemistry. II. 9-Deoxy-4(R)-dihydrospectinomycin and 9-deoxyspectinomycin. J. Antibiot. 31 (10), 979-984.
12. Rosenbrook, W., Jr., Carney, R. E., Egan, R. S., Stanaszek, R. S., Cirovic, M., Nishinaga, T., Mochida, K., and Mori, Y. (1978) Spectinomycin modification. IV. 7-Deoxy-4(R)-dihydrospectinomycin. J. Antibiot. 31 (5), 451-455.
13. Thomas, R. C., and Fritzen, E. L. (1985) Spectinomycin modification. III. Spectinomycin analogs with C-3′-branched chain sugars. J. Antibiot. 38 (2), 208-219.
14. White, D. R., Maring, C. J., and Cain, G. A. (1983) Synthesis and in vitro antibacterial properties of alkylspectinomycin analogs. J. Antibiot. 36 (3), 339-342.
15. Woitun, E., Maier, R., Wetzel, B., Reuter, W., and Lechner, U. (1981) Modification of spectinomycin. 2. Derivatives of 4-dihydro-4-deoxy-4(R)-aminospectinomycin. J. Antibiot. 34 (1), 22-27.
16. Bruhn, D. F., Waidyarachchi, S. L., Madhura, D. B., Shcherbakov, D., Zheng, Z., Liu, J., Abdelrahman, Y. M., Singh, A. P., Duscha, S., Rathi, C., Lee, R. B., Belland, R. J., Meibohm, B., Rosch, J. W., Bottger, E. C., and Lee, R. E. (2015) Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections. Sci. Transl. Med. 7 (288), 288ra75.
17. Adams, K. N., Takaki, K., Connolly, L. E., Wiedenhoft, H., Winglee, K., Humbert, O., Edelstein, P. H., Cosma, C. L., and Ramakrishnan, L. (2011) Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell 145 (1), 39-53.
18. Madhura, D. B., Liu, J., Meibohm, B., and Lee, R. E. (2016) Phase II Metabolic Pathways of Spectinamide Antitubercular Agents: A Comparative Study of the Reactivity of 4-Substituted Pyridines to Glutathione Conjugation. MedChemComm 7 (1), 114-117.
19. Madhura, D. B., Lee, R., and Meibohm, B. (2013) Pharmacokinetic profile of spectinomycin in rats. Pharmazie 68 (8), 675-676.
20. Bruhn, D. F., Scherman, M. S., Liu, J., Scherbakov, D., Meibohm, B., Bottger, E. C., Lenaerts, A. J., and Lee, R. E. (2015) In vitro and in vivo Evaluation of Synergism between Anti-Tubercular Spectinamides and Non-Classical Tuberculosis Antibiotics. Sci. Rep. 5, 13985.
21. Herrinton, P. M., Klotz, K. L., and Hartley, W. M. (1993) Oxidation and Alkylation of Spectinomycin Derivatives - Synthesis of Trospectomycin from Spectinomycin. J. Org. Chem. 58 (3), 678-682.
22. Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., Repasky, M. P., Knoll, E. H., Shelley, M., Perry, J. K., Shaw, D. E., Francis, P., and Shenkin, P. S. (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47 (7), 1739-1749.
23. Case, D. A., Darden, T. A., Cheatham, T. E., and Cheatham, I. AMBER 11, University of California, San Francisco, 2010.
24. Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., and Case, D. A. (2004) Development and testing of a general amber force field. J. Comput. Chem. 25 (9), 1157-1174.
25. Aqvist, J. (1990) Ion Water Interaction Potentials Derived from Free-Energy Perturbation Simulations. J. Phys. Chem. 94 (21), 8021-8024.
26. Bruell, C. M., Eichholz, C., Kubarenko, A., Post, V., Katunin, V. I., Hobbie, S. N., Rodnina, M. V., and Bottger, E. C. (2008) Conservation of bacterial protein synthesis machinery: initiation and elongation in Mycobacterium smegmatis. Biochemistry 47 (34), 8828-8839.
27. Hurdle, J. G., Lee, R. B., Budha, N. R., Carson, E. I., Qi, J., Scherman, M. S., Cho, S. H., McNeil, M. R., Lenaerts, A. J., Franzblau, S. G., Meibohm, B., and Lee, R. E. (2008) A microbiological assessment of novel nitrofuranylamides as anti-tuberculosis agents. J. Antimicrob. Chemother. 62 (5), 1037-1045.
28. Rakesh, Bruhn, D., Madhura, D. B., Maddox, M., Lee, R. B., Trivedi, A., Yang, L., Scherman, M. S., Gilliland, J. C., Gruppo, V., McNeil, M. R., Lenaerts, A. J., Meibohm, B., and Lee, R. E. (2012) Antitubercular nitrofuran isoxazolines with improved pharmacokinetic properties. Bioorg. Med. Chem. 20 (20), 6063-6072.
29. North, E. J., Scherman, M. S., Bruhn, D. F., Scarborough, J. S., Maddox, M. M., Jones, V., Grzegorzewicz, A., Yang, L., Hess, T., Morisseau, C., Jackson, M., McNeil, M. R., and Lee, R. E. (2013) Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties. Bioorg. Med. Chem. 21 (9), 2587-2599.
30. Lenaerts, A. J. M., Gruppo, V., Brooks, J. V., and Orme, I. M. (2003) Rapid in vivo screening of experimental drugs for tuberculosis using gamma interferon gene-disrupted mice. Antimicrob. Agents Chemother. 47 (2), 783-785.