Antiinfectives targeting enzymes and the proton motive force

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 51, 2015, Pages E7073-E7082

  Feng, Xinxin ^a   Zhu, Wei ^a   Schurig Briccio, Lici A ^a   Lindert, Steffen ^b   Shoen, Carolyn ^c   Hitchings, Reese ^d   Li, Jikun ^a   Wang, Yang ^a   Baig, Noman ^a   Zhou, Tianhui ^a   Kim, Boo Kyung ^a   Crick, Dean C ^d   Cynamon, Michael ^c   McCammon, J Andrew ^a,e   Gennis, Robert B ^a   Oldfield, Eric ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c Central New York Research Corporation   (United States)

^d Department of Ecosystem Science and Sustainability   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Bedaquiline; Clofazimine; Clomiphene; Molecular dynamics simulations; Vacquinol

Indexed keywords

2,4 DINITROPHENOL; AFIMOXIFENE; AMIODARONE; ANTIINFECTIVE AGENT; AU 1235; BAM 15; BEDAQUILINE; BM 212; BPH 1330; BPH 889; CLOFAZIMINE; CLOMIFENE; CLOSANTEL; CLOZAFIMINE; DRONEDARONE; ETHANOLAMINE; N (2 ADAMANTYL) N' GERANYLETHYLENEDIAMINE; NICLOSAMIDE; NITAZOXANIDE; PLANTENSIMYCIN; PYRAZINOIC ACID; QUININE DERIVATIVE; RALOXIFENE; RO 48 8071; SULFAMETHOXAZOLE; TAMOXIFEN; THPP 2; TIZOXANIDE; TRIMETHOPRIM; UNCLASSIFIED DRUG; VACQUINOL; ENZYME INHIBITOR; PIPERIDINE DERIVATIVE; QUINOLINE DERIVATIVE; TRANSFERASE; UNCOUPLING PROTEIN; UNDECAPRENYL PYROPHOSPHATE SYNTHETASE; VACQUINOL-1;

ANTIBACTERIAL ACTIVITY; ANTIFUNGAL ACTIVITY; ARTICLE; BREAST CANCER; CESTODIASIS; CONTROLLED STUDY; CRYPTOSPORIDIUM PARVUM; DIFFERENTIAL SCANNING CALORIMETRY; DRUG MECHANISM; ELECTRON SPIN RESONANCE; FATTY LIVER; GIARDIA INTESTINALIS; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; LIPOPHILICITY; MOLECULAR DYNAMICS; MYCOBACTERIUM TUBERCULOSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; PROTON MOTIVE FORCE; SACCHAROMYCES CEREVISIAE; STAPHYLOCOCCUS AUREUS; ANTAGONISTS AND INHIBITORS; BIOPHYSICS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; ENZYMOLOGY; GROWTH, DEVELOPMENT AND AGING; HUMAN; MOLECULAR MODEL;

ALKYL AND ARYL TRANSFERASES; ANTI-INFECTIVE AGENTS; BIOPHYSICAL PHENOMENA; CLOMIPHENE; DRUG DISCOVERY; ENZYME INHIBITORS; HUMANS; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; MOLECULAR STRUCTURE; MYCOBACTERIUM TUBERCULOSIS; PIPERIDINES; PROTON-MOTIVE FORCE; QUINOLINES; STAPHYLOCOCCUS AUREUS; UNCOUPLING AGENTS;

EID: 84952671080     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1521988112     Document Type: Article

References (92)

1. Anonymous (2013) Dictionary of Natural Products on DVD (Chapman & Hall/CRC, London).
2. Oldfield E, Lin FY (2012) Terpene biosynthesis: Modularity rules. Angew Chem Int Ed Engl 51(5):1124-1137.
3. CDC (2013) Antibiotic Resistance Threats in the US. Available at www.cdc.gov/features/AntibioticResistanceThreats/index.html. Accessed November 21, 2015.
4. Taylor J, et al. (2014) Estimating the economic costs of antimicrobial resistance. Available at www.rand.org/pubs/research-reports/RR911.html. Accessed November 21, 2015.
5. East SP, Silver LL (2013) Multitarget ligands in antibacterial research: Progress and opportunities. Expert Opin Drug Discov 8(2):143-156.
6. Oldfield E, Feng X (2014) Resistance-resistant antibiotics. Trends Pharmacol Sci 35(12):664-674.
7. WHO (2015) Global tuberculosis report 2015. Available at www.who.int/tb/publications/global-report/en/). Accessed November 21, 2015.
8. Zumla AI, et al. (2014) New antituberculosis drugs, regimens, and adjunct therapies: Needs, advances, and future prospects. Lancet Infect Dis 14(4):327-340.
9. Andries K, et al. (2005) A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307(5707):223-227.
10. Protopopova M, et al. (2005) Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1, 2-ethylenediamines. J Antimicrob Chemother 56(5):968-974.
11. Zumla A, Nahid P, Cole ST (2013) Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov 12(5):388-404.
12. Tahlan K, et al. (2012) SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother 56(4):1797-1809.
13. Li K, et al. (2014) Multitarget drug discovery for tuberculosis and other infectious diseases. J Med Chem 57(7):3126-3139.
14. Benaim G, et al. (2006) Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem 49(3):892-899.
15. Benaim G, et al. (2014) Dronedarone, an amiodarone analog with improved anti-Leishmania mexicana efficacy. Antimicrob Agents Chemother 58(4):2295-2303.
16. Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biol Rev Camb Philos Soc 41(3):445-502.
17. Mitchell P (1972) Chemiosmotic coupling in energy transduction: A logical development of biochemical knowledge. J Bioenerg 3(1):5-24.
18. Benaim G, Paniz Mondolfi AE (2012) The emerging role of amiodarone and dronedarone in Chagas disease. Nat Rev Cardiol 9(10):605-609.
19. Veiga-Santos P, et al. (2015) SQ109, a new drug lead for Chagas disease. Antimicrob Agents Chemother 59(4):1950-1961.
20. Li W, et al. (2014) Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis. Antimicrob Agents Chemother 58(11):6413-6423.
21. Thoma R, et al. (2004) Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase. Nature 432(7013):118-122.
22. Sacksteder KA, Protopopova M, Barry CE, 3rd, Andries K, Nacy CA (2012) Discovery and development of SQ109: A new antitubercular drug with a novel mechanism of action. Future Microbiol 7(7):823-837.
23. Woods RA, Bard M, Jackson IE, Drutz DJ (1974) Resistance to polyene antibiotics and correlated sterol changes in two isolates of Candida tropicalis from a patient with an amphotericin B-resistant funguria. J Infect Dis 129(1):53-58.
24. Ling LL, et al. (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517(7535):455-459.
25. Goldman RC (2013) Why are membrane targets discovered by phenotypic screens and genome sequencing in Mycobacterium tuberculosis? Tuberculosis (Edinb) 93(6):569-588.
26. Stock U, et al. (2013) Measuring interference of drug-like molecules with the respiratory chain: Toward the early identification of mitochondrial uncouplers in lead finding. Assay Drug Dev Technol 11(7):408-422.
27. WHO (2014) Global network to support countries tackle rising tapeworm infection. Available at www.who.int/neglected-diseases/global-network-tackle-tapeworm/en/. Accessed November 21, 2015.
28. White CA, Jr (2004) Nitazoxanide: A new broad spectrum antiparasitic agent. Expert Rev Anti Infect Ther 2(1):43-49.
29. Makobongo MO, Einck L, Peek RM, Jr, Merrell DS (2013) In vitro characterization of the anti-bacterial activity of SQ109 against Helicobacter pylori. PLoS One 8(7):e68917.
30. De Carvalho LP, Lin G, Jiang X, Nathan C (2009) Nitazoxanide kills replicating and nonreplicating Mycobacterium tuberculosis and evades resistance. J Med Chem 52(19):5789-5792.
31. De Carvalho LP, Darby CM, Rhee KY, Nathan C (2011) Nitazoxanide disrupts membrane potential and intrabacterial pH homeostasis of Mycobacterium tuberculosis. ACS Med Chem Lett 2(11):849-854.
32. Shigyo K, et al. (2013) Efficacy of nitazoxanide against clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 57(6):2834-2837.
33. Lam KK, et al. (2012) Nitazoxanide stimulates autophagy and inhibits mTORC1 signaling and intracellular proliferation of Mycobacterium tuberculosis. PLoS Pathog 8(5):e1002691.
34. Tao H, Zhang Y, Zeng X, Shulman GI, Jin S (2014) Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med 20(11):1263-1269.
35. Wang YC, et al. (2013) Drug screening identifies niclosamide as an inhibitor of breast cancer stem-like cells. PLoS One 8(9):e74538.
36. Imperi F, et al. (2013) New life for an old drug: The anthelmintic drug niclosamide inhibits Pseudomonas aeruginosa quorum sensing. Antimicrob Agents Chemother 57(2):996-1005.
37. Perry RJ, et al. (2013) Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler. Cell Metab 18(5):740-748.
38. Perry RJ, Zhang D, Zhang XM, Boyer JL, Shulman GI (2015) Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science 347(6227):1253-1256.
39. Via LE, et al. (2015) Host-mediated bioactivation of pyrazinamide: Implications for efficacy, resistance, and therapeutic alternatives. ACS Infect Dis 1(5):203-214.
40. Speirs RJ, Welch JT, Cynamon MH (1995) Activity of n-propyl pyrazinoate against pyrazinamide-resistant Mycobacterium tuberculosis: Investigations into mechanism of action of and mechanism of resistance to pyrazinamide. Antimicrob Agents Chemother 39(6):1269-1271.
41. Cholo MC, Steel HC, Fourie PB, Germishuizen WA, Anderson R (2012) Clofazimine: Current status and future prospects. J Antimicrob Chemother 67(2):290-298.
42. Karat ABA, Jeevaratnam A, Karat S, Rao PSS (1970) Double-blind controlled clinical trial of clofazimine in reactive phases of lepromatous leprosy. BMJ 1(5690):198-200.
43. Grant SS, Kaufmann BB, Chand NS, Haseley N, Hung DT (2012) Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals. Proc Natl Acad Sci USA 109(30):12147-12152.
44. Lechartier B, Cole ST (2015) Mode of action of clofazimine and combination therapy with benzothiazinones against Mycobacterium tuberculosis. Antimicrob Agents Chemother 59(8):4457-4463.
45. Hards K, et al. (2015) Bactericidal mode of action of bedaquiline. J Antimicrob Chemother 70(7):2028-2037.
46. Rokitskaya TI, Ilyasova TM, Severina II, Antonenko YN, Skulachev VP (2013) Electrogenic proton transport across lipid bilayer membranes mediated by cationic derivatives of rhodamine 19: Comparison with anionic protonophores. Eur Biophys J 42(6):477-485.
47. Nagamune H, et al. (1993) The lipophilic weak base (Z)-5-methyl-2-[2-(1-naphthyl) ethenyl]-4-piperidinopyridine (AU-1421) is a potent protonophore type cationic uncoupler of oxidative phosphorylation in mitochondria. Biochim Biophys Acta 1141(2-3):231-237.
48. Chen F-C, et al. (2014) Pros and cons of the tuberculosis drugome approach.an empirical analysis. PLoS One 9(6):e100829.
49. Zhu W, et al. (2013) Antibacterial drug leads targeting isoprenoid biosynthesis. Proc Natl Acad Sci USA 110(1):123-128.
50. Larsen SD, et al. (2006) Discovery and initial development of a novel class of antibacterials: Inhibitors of Staphylococcus aureus transcription/translation. Bioorg Med Chem Lett 16(24):6173-6177.
51. Peukert S, et al. (2008) Design and structure-activity relationships of potent and selective inhibitors of undecaprenyl pyrophosphate synthase (UPPS): Tetramic, tetronic acids and dihydropyridin-2-ones. Bioorg Med Chem Lett 18(6):1840-1844.
52. Zhang Y, et al. (2012) HIV-1 integrase inhibitor-inspired antibacterials targeting isoprenoid biosynthesis. ACS Med Chem Lett 3(5):402-406.
53. Wang J, et al. (2006) Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature 441(7091):358-361.
54. Wu M, et al. (2011) Antidiabetic and antisteatotic effects of the selective fatty acid synthase (FAS) inhibitor platensimycin in mouse models of diabetes. Proc Natl Acad Sci USA 108(13):5378-5383.
55. Davies Forsman L, et al. (2014) Intra- and extracellular activities of trimethoprimsulfamethoxazole against susceptible and multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 58(12):7557-7559.
56. Blein JP, Ducruet JM, Gauvrit C (1979) Identification and biological-activity of an impurity of technical Diuron. Weed Res 19(2):117-121.
57. Routaboul JM, et al. (1991) Effects of N, N'-bis-(4-trifluoromethylphenyl)-urea on isolated plant-mitochondria and thylakoid membranes. Phytochemistry 30(3):733-738.
58. Brown JR, et al. (2011) The structure-activity relationship of urea derivatives as antituberculosis agents. Bioorg Med Chem 19(18):5585-5595.
59. Kenwood BM, et al. (2014) Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol Metab 3(2):114-123.
60. Farha MA, Verschoor CP, Bowdish D, Brown ED (2013) Collapsing the proton motive force to identify synergistic combinations against Staphylococcus aureus. Chem Biol 20(9):1168-1178.
61. Singh AP, Nicholls P (1985) Cyanine and safranine dyes as membrane potential probes in cytochrome c oxidase reconstituted proteoliposomes. J Biochem Biophys Methods 11(2-3):95-108.
62. Gange DM, Donovan S, Lopata RJ, Henegar K (1995) The QSAR of insecticidal uncouplers. Classical and Three-Dimensional QSAR in Agrochemistry, ACS Symposium Series, eds Hansch C, Fujita T, Vol 606, pp 199-212.
63. Brennan PJ, Nakaido H (1995) The envelope of mycobacteria. Annu Rev Biochem 64:29-63.
64. Oldfield E, Chapman D (1971) Effects of cholesterol and cholesterol derivatives on hydrocarbon chain mobility in lipids. Biochem Biophys Res Commun 43(3):610-616.
65. Kelley LA, Sternberg MJ (2009) Protein structure prediction on the Web: A case study using the Phyre server. Nat Protoc 4(3):363-371.
66. Cheng W, Li W (2014) Structural insights into ubiquinone biosynthesis in membranes. Science 343(6173):878-881.
67. Lin F-Y, et al. (2012) Head-to-head prenyl tranferases: Anti-infective drug targets. J Med Chem 55(9):4367-4372.
68. Guo R-T, et al. (2007) Bisphosphonates target multiple sites in both cis- and transprenyltransferases. Proc Natl Acad Sci USA 104(24):10022-10027.
69. Wang W, et al. (2008) The structural basis of chain length control in Rv1086. J Mol Biol 381(1):129-140.
70. Chan HC, et al. (2014) Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from Mycobacterium tuberculosis. J Am Chem Soc 136(7):2892-2896.
71. Farha MA, et al. (2015) Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase. Proc Natl Acad Sci USA 112(35):11048-11053.
72. Jacobs AC, et al. (2013) Adenylate kinase release as a high-throughput-screeningcompatible reporter of bacterial lysis for identification of antibacterial agents. Antimicrob Agents Chemother 57(1):26-36.
73. Derbyshire ER, Prudencio M, Mota MM, Clardy J (2012) Liver-stage malaria parasites vulnerable to diverse chemical scaffolds. Proc Natl Acad Sci USA 109(22):8511-8516.
74. Layre E, et al. (2014) Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c. Proc Natl Acad Sci USA 111(8):2978-2983.
75. Young DC, et al. (2015) In vivo biosynthesis of terpene nucleosides provides unique chemical markers of Mycobacterium tuberculosis infection. Chem Biol 22(4):516-526.
76. Pethe K, et al. (2004) Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation. Proc Natl Acad Sci USA 101(37):13642-13647.
77. Kim MO, et al. (2015) A Molecular Dynamics Investigation of Mycobacterium tuberculosis Prenyl Synthases: Conformational Flexibility and Implications for Computeraided Drug Discovery. Chem Biol Drug Des 85(6):756-769.
78. Baell JB, Holloway GA (2010) New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem 53(7):2719-2740.
79. Yang X, et al. (2014) Prevention of multidrug resistance (MDR) in osteosarcoma by NSC23925. Br J Cancer 110(12):2896-2904.
80. Kitambi SS, et al. (2014) Vulnerability of glioblastoma cells to catastrophic vacuolization and death induced by a small molecule. Cell 157(2):313-328.
81. Brown RF, et al. (1946) alpha-(2-Piperidyl)-2-aryl-4-quinolinemethanols. J Am Chem Soc 68(12):2705-2708.
82. Mead JF, Senear AE, Koepfli JB (1946) The synthesis of potential antimalarials; 2-alkylalpha-(2-piperidyl)-4-quinolinemethanols. J Am Chem Soc 68(12):2708-2710.
83. Duan Z, et al. (2012) Synthesis and evaluation of (2-(4-methoxyphenyl)-4-quinolinyl) (2-piperidinyl) methanol (NSC23925) isomers to reverse multidrug resistance in cancer. J Med Chem 55(7):3113-3121.
84. Duan Z, Choy E, Hornicek FJ (2009) NSC23925, identified in a high-throughput cellbased screen, reverses multidrug resistance. PLoS One 4(10):e7415.
85. Rybniker J, et al. (2015) Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. Nat Commun 6:7659.
86. Sjostrom JE, Kuhler T, Larsson H (1997) Basis for the selective antibacterial activity in vitro of proton pump inhibitors against Helicobacter spp. Antimicrob Agents Chemother 41(8):1797-1801.
87. Tsutsui N, et al. (2000) A novel action of the proton pump inhibitor rabeprazole and its thioether derivative against the motility of Helicobacter pylori. Antimicrob Agents Chemother 44(11):3069-3073.
88. Ohara T, et al. (2001) Inhibitory action of a novel proton pump inhibitor, rabeprazole, and its thioether derivative against the growth and motility of clarithromycinresistant Helicobacter pylori. Helicobacter 6(2):125-129.
89. Fryklund J, Wallmark B (1986) Sulfide and sulfoxide derivatives of substituted benzimidazoles inhibit acid formation in isolated gastric glands by different mechanisms. J Pharmacol Exp Ther 236(1):248-253.
90. Lu P, et al. (2011) Pyrazinoic acid decreases the proton motive force, respiratory ATP synthesis activity, and cellular ATP levels. Antimicrob Agents Chemother 55(11):5354-5357.
91. Li K, et al. (2015) Oxa, thia, heterocycle, and carborane analogues of SQ109: Bacterial and protozoal cell growth inhibitors. ACS Infect Dis 1(5):215-221.
92. Gostimskaya I, Galkin A (2010) Preparation of highly coupled rat heart mitochondria. J Vis Exp, 10.3791/220.