AFN-1252 is a potent inhibitor of enoyl-ACP reductase from Burkholderia pseudomallei - Crystal structure, mode of action, and biological activity

Protein Science

Volumn 24, Issue 5, 2015, Pages 832-840

  Narasimha Rao, Krishnamurthy ^a   Lakshminarasimhan, Anirudha ^a   Joseph, Sarah ^a   Lekshmi, Swathi U ^a   Lau, Ming Seong ^b   Takhi, Mohammed ^c   Sreenivas, Kandepu ^c   Nathan, Sheila ^b   Yusof, Rohana ^d   Abd Rahman, Noorsaadah ^d   Ramachandra, Murali ^a   Antony, Thomas ^a   Subramanya, Hosahalli ^a  

^a Aurigene Discovery Technologies Limited   (India)

^b UNIVERSITI KEBANGSAAN MALAYSIA   (Malaysia)

^c Pharmaceutical Development   (India)

^d UNIVERSITY OF MALAYA   (Malaysia)

Author keywords

AFN 1252; Burkholderia pseudomallei; FabI; Melioidosis

Indexed keywords

AFN 1252; MONOMER; OXIDOREDUCTASE INHIBITOR; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; API 1252; BENZOFURAN DERIVATIVE; ENOYL ACYL CARRIER PROTEIN REDUCTASE (NADH); PYRONE DERIVATIVE;

ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL GROWTH; BIOLOGICAL ACTIVITY; BURKHOLDERIA PSEUDOMALLEI; COMPLEX FORMATION; CRYSTAL STRUCTURE; DRUG MECHANISM; DRUG PROTEIN BINDING; ENZYME INACTIVATION; GROWTH INHIBITION; IC50; MELIOIDOSIS; PRIORITY JOURNAL; PROTEIN QUATERNARY STRUCTURE; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; ENZYMOLOGY; HUMAN; KINETICS; METABOLISM; MICROBIOLOGY; STAPHYLOCOCCAL INFECTIONS; X RAY CRYSTALLOGRAPHY;

ANTI-BACTERIAL AGENTS; BENZOFURANS; BURKHOLDERIA PSEUDOMALLEI; CRYSTALLOGRAPHY, X-RAY; ENOYL-(ACYL-CARRIER-PROTEIN) REDUCTASE (NADH); HUMANS; KINETICS; MELIOIDOSIS; PYRONES; STAPHYLOCOCCAL INFECTIONS;

EID: 84956798676     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1002/pro.2655     Document Type: Article

References (43)

1. Hayden HS, Lim R, Brittnacher MJ, Sims EH, Ramage ER, Fong C, Wu Z, Crist E, Chang J, Zhou Y, Radey M, Rohmer L, Haugen E, Gillett W, Wuthiekanun V, Peacock SJ, Kaul R, Miller SI, Manoil C, Jacobs MA, (2012) Evolution of Burkholderia pseudomallei in Recurrent Melioidosis. PLoS One 7 (5): e36507, 1-14.
2. Limmathurotsakul D, Thammasart S, Warrasuth N, Thapanagulsak P, Jatapai A, Pengreungrojanachai V, Anun S, Joraka W, Thongkamkoon P, Saiyen P, Wongratanacheewin S, Day NP, Peacock SJ, (2012) Melioidosis in animals, Thailand, 2006-2010. Emerg Infect Dis 18 (2): 325-327.
3. Wiersinga WJ, Currie BJ, Peacock SJ, (2012) Melioidosis. N Engl J Med 367 (11): 1035-1044.
4. Limmathurotsakul D, Peacock SJ, (2011) Melioidosis: a clinical overview. Br Med Bull 99: 125-139.
5. Cheng AC, Currie BJ, Dance DA, Funnell SG, Limmathurotsakul D, Simpson AJ, Peacock SJ, (2013) Clinical definitions of melioidosis. Am J Trop Med Hyg 88 (3): 411-413.
6. Dance D, (2014) Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents 43 (4): 310-318.
7. Estes DM, Dow SW, Schweizer HP, Torres AG, (2010) Present and future therapeutic strategies for melioidosis and glanders. Expert Rev Anti Infect Ther 8 (3): 325-338.
8. Schweizer HP, (2012) Mechanisms of antibiotic resistance in Burkholderia pseudomallei: implications for treatment of melioidosis. Future Microbiol 7 (12): 1389-1399.
9. Sarovich DS, Price EP, Limmathurotsakul D, Cook JM, Von Schulze AT, Wolken SR, Keim P, Peacock SJ, Pearson T, (2012) Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection. Infect Drug Resist 5: 129-132.
10. Moore RA, DeShazer D, Reckseidler S, Weissman A, Woods DE, (1999) Efflux-mediated aminoglycoside and macrolide resistance in Burkholderia pseudomallei. Antimicrob Agents Chemother 43 (3): 465-470.
11. Campbell JW, Cronan JE Jr, (2001) Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery. Annu Rev Microbiol 55: 305-332.
12. Parsons JB, Rock CO, (2011) Is bacterial fatty acid synthesis a valid target for antibacterial drug discovery? Curr Opin Microbiol 14: 544-549.
13. Brinster S, Lamberet G, Staels B, Trieu-Cuot P, Gruss A, Poyart C, (2009) Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens. Nature 458 (7234): 83-86.
14. Parsons JB, Frank MW, Subramanian C, Saenkham P, Rock CO,. (2011) Metabolic basis for the differential susceptibility of Gram-positive pathogens to fatty acid synthesis inhibitors Proc Natl Acad Sci USA 108 (37): 15378-15383.
15. Wang Y, Ma S, (2013) Recent advances in inhibitors of bacterial fatty acid synthesis type II (FASII) system enzymes as potential antibacterial agents. Chem Med Chem 8 (10): 1589-1608.
16. Cummings JE, Kingry LC, Rholl DA, Schweizer HP, Tonge PJ, Slayden RA, (2014) The Burkholderia pseudomallei enoyl-acyl carrier protein reductase FabI1 is essential for in vivo growth and is the target of a novel chemotherapeutic with efficacy. Antimicrob Agents and Chemother 58 (2): 931-935.
17. Lu H, Tonge PJ, (2008) Inhibitors of FabI, an enzyme drug target in the bacterial fatty acid biosynthesis pathway. Acc Chem Res 41 (1): 11-20.
18. Heath RJ, Yu Y, Shapiro MA, Olson E, Rock CO, (1998) Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis. J Biol Chem 273: 30316-30320.
19. Takhi M, Sreenivas K, Reddy CK, Munikumar M, Praveena K, Sudheer P, Rao BN, Ramakanth G, Sivaranjani J, Mulik S, Reddy YR, Narasimha Rao K, Pallavi R, Lakshminarasimhan A, Panigrahi SK, Antony T, Abdullah I, Lee YK, Ramachandra M, Yusof R, Rahman NA, Subramanya H, (2014) Discovery of azetidine based ene-amides as potent bacterial enoyl-ACP reductase (FabI) inhibitors. Eur J Med Chem 84: 382-394.
20. Miller WH, Seefeld MA, Newlander KA, Uzinskas IN, Burgess WJ, Heerding DA, Yuan CC, Head MS, Payne DJ, Rittenhouse SF, Moore TD, Pearson SC, Berry V, DeWolf WE Jr, Keller PM, Polizzi BJ, Qiu X, Janson CA, Huffman WF, (2002) Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI). J Med Chem 45: 3246-3256.
21. Tsuji BT, Harigaya Y, Lesse AJ, Forrest A, Ngo D, (2010) Mechanism and inhibition of the FabV enoyl-ACP reductase from Burkholderia Malle. Biochemistry 49: 1281-1289.
22. Tsuji BT, Harigaya Y, Lesse AJ, Forrest A, Ngo D, (2013) Activity of AFN-1252 -a novel FabI inhibitor, against Staphylococcus aureus in an in vitro pharmacodynamic model simulating human pharmacokinetics. J Chemother 25 (1): 32-35.
23. Kumar K, Chopra S, (2013) New drugs for methicillin-resistant Staphylococcus aureus: an update. J Antimicrob Chemother 68 (7): 1465-1470.
24. Kaplan N, Garner C, Hafkin B, (2013) AFN-1252 in vitro absorption studies and pharmacokinetics following microdosing in healthy subjects. Eur J Pharm Sci 50 (3-4): 440-446.
25. Kaplan N, Hafkin B, (2014) Preclinical Pharmacokinetics and Efficacy of Debio 1450 (Previously AFN-1720), a Prodrug of the Staphylococcal-specific Antibiotic Debio 1452 (Previously AFN-1252) ECCMID 2014, Barcelona, Spain.
26. Kaplan N, Albert M, Awrey D, Bardouniotis E, Berman J, Clarke T, Dorsey M, Hafkin B, Ramnauth J, Romanov V, Schmid MB, Thalakada R, Yethon J, Pauls HW, (2012) Mode of action, in vitro activity and in vivo efficacy of AFN-1252, a selective antistaphylococcal FabI inhibitor. Antimicrob Agents Chemother 56: 5865-5874.
27. Karlowsky JA, Kaplan N, Hafkin B, Hoban DJ, Zhanel GG, (2009) AFN-1252, a FabI inhibitor, demonstrates a staphylococcus-specific spectrum of activity. Antimicrob Agents Chemother 53: 3544-3548.
28. Yao J, Maxwell JB, Rock CO, (2013) Resistance to AFN-1252 arises from enoyl-acyl carrier protein reductase (FabI) missense mutations in Staphylococcus aureus. J Biol Chem 288: 36261-36271.
29. Yao J, Abdelrahman YM, Robertson RM, Cox JV, Belland RJ, White SW, Rock CO, (2014) Type II fatty acid synthesis is essential for the replication of Chlamydia trachomatis. J Biol Chem 289 (32): 22365-22376.
30. Escalada MG, Harwood JL, Maillard JY, Ochs D, (2005) Triclosan inhibition of fatty acid synthesis and its effect on growth of Escherichia coli and Pseudomonas aeruginosa. J Antimicrob Chemother 55: 879-882.
31. Heath RJ, Rubin JR, Holland DR, Zhang E, Snow ME, Rock CO, (1999) Mechanism of triclosan inhibition of bacterial fatty acid synthesis. J Biol Chem 274: 11110-11114.
32. Gerusz V, Denis A, Faivre F, Bonvin Y, Oxoby M, Briet S, LeFralliec G, Oliveira C, Desroy N, Raymond C, Peltier L, Moreau F, Escaich S, Vongsouthi V, Floquet S, Drocourt E, Walton A, Prouvensier L, Saccomani M, Durant L, Genevard JM, Sam-Sambo V, Soulama-Mouze C, (2012) From triclosan toward the clinic: discovery of nonbiocidal, potent FabI inhibitors for the treatment of resistant bacteria. J Med Chem 55: 9914-9928.
33. Liu N, Cummings JE, England K, Slayden RA, Tonge PJ, (2011) Mechanism and inhibition of the FabI enoyl-ACP reductase from Burkholderia pseudomallei. J Antimicrob Chemother 66: 564-573.
34. DeLano WL, (2002) The PyMOL molecular graphics system on World Wide Web. Version 1.5.0.4 Schrodinger LLC. Accession date 2013. Available at: http://www.pymol.org.
35. Schiebel J, Chang A, Shah S, Lu Y, Liu L, Pan P, Hirschbeck MW, Tareilus M, Eltschkner S, Yu W, Cummings JE, Knudson SE, Bommineni GR, Walker SG, Slayden RA, Sotriffer CA, Tonge PJ, Kisker C, (2014) Rational design of broad-spectrum antibacterial activity based on a clinically relevant enoyl-ACP reductase inhibitor. J Biol Chem 289 (23): 15987-16005.
36. Beveridge TJ, (1999) Structures of gram-negative cell walls and their derived membrane vesicles. J Bacteriol 181 (16): 4725-4733.
37. Helmut B, Sandra F, Gregor H, Friederike T, (1996) The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA. Eur J Biochem 24: 689-694.
38. Pauls H, Ramnauth J, (2013) Salts, prodrugs and polymorphs of FabI inhibitors. WO 2008098374 A1.
39. Wiegand I, Hilpert K, Hancock RE, (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nature Protoc 3 (2): 163-175.
40. Lee SH, Chong CE, Lim BS, Chai SJ, Sam KK, Mohamed R, Nathan S, (2007) Burkholderia pseudomallei animal and human isolates from Malaysia exhibit different phenotypic characteristics. Diagn Microbiol Infect Dis 58(3): 263-70.
41. Otwinowski Z, Minor W, (1997) Methods in enzymology. Macromolecular crystallography, Part B, New York: Academic Press, Vol. 276, pp 307-326.
42. Murshudov GN, Vagin AA, Dodson EJ, (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53: 240-255.
43. Emsley P, Lokhamp B, Scott WG, Cowtan K, (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66: 486-501.