Citation: Chen-Yu Ling, Yun-Liang Tao, Wen-Jing Chu, Hui Wang, Hai-Dong Wang, Yu-She Yang. Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain[J]. Chinese Chemical Letters, ;2016, 27(02): 235-240. doi: 10.1016/j.cclet.2015.09.019 shu

Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain

a.
a. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
b.
b. School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China;
c.
c. Department of Microbiology, China Pharmaceutical University, Nanjing 210009, China

Corresponding author: Hai-Dong Wang, Yu-She Yang,
Received Date: 10 March 2015
Available Online: 15 June 2015

A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12a, 12d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.
- Multi-drug resistant bacteria,
- Pleuromutilin,
- 4H-Pyran-4-one,
- Antibacterial activity
1. [1]
  [1] B. Spellberg, R. Guidos, D. Gilbert, et al., The epidemic of antibiotic-resistant infections: a call to action for the medical community from the infectious diseases society of America, Clin. Infect. Dis. 46 (2008) 155-164.
2. [2]
  [2] H.W. Boucher, G.H. Talbot, J.S. Bradley, et al., Bad bugs, no drugs: no ESKAPE! An update from the infectious diseases society of America, Clin. Infect. Dis. 48 (2009) 1-12.
3. [3]
  [3] T. Alexander, Antibiotic-resistance in Streptococcus pneumoniae, Clin. Infect. Dis. 24 (1997) S85-S88.
4. [4]
  [4] Y. Cetinkaya, P. Falk, C.G. Mayhall, Vancomycin-resistant Enterococci, Clin. Microbiol. Rev. 13 (2000) 686-707.
5. [5]
  [5] F. Kavanagh, A. Hervey, W.J. Robbins, Antibiotic substances from basidiomycetes. VⅢ. Pleurotus multilus (Fr.) sacc. and Pleurotus passeckerianus pilat, Proc. Natl. Acad. Sci. U. S. A. 37 (1951) 570-574.
6. [6]
  [6] L.A. Hodgin, G. Högenauer, The mode of action of pleuromutilin derivatives, Eur. J. Biochem. 47 (1970) 527-533.
7. [7]
  [7] H. Egger, H. Reinshagen, New pleuromutilin derivatives with enhanced antimicrobial activity. Ⅱ. Structure-activity correlations, J. Antibiot. 29 (1976) 923-927.
8. [8]
  [8] G. Laber, E. Schütze, In vivo efficacy of 81.723 hfu, a new pleuromutilin derivative against experimentally induced airsacculitis in chicks and turkey poults, Antimicrob. Agents Chemother. 7 (1975) 517-521.
9. [9]
  [9] P.C.T. Hannan, H.M. Windsor, P.H. Ripley, In vitro susceptibilities of recent field isolates of Mycoplasma hyopneumoniae and Mycoplasma hyosynoviae to valnemulin (Econor®), tiamulin and enrofloxacin and the in vitro development of resistance to certain antimicrobial agents in Mycoplasma hyopneumoniae, Res. Vet. Sci. 63 (1997) 157-160.
10. [10]
  [10] R.S. Daum, S. Kar, P. Kirkpatrick, Retapamulin, Nat. Rev. Drug Discov. 6 (2007) 865-866.
11. [11]
  [11] R. Novak, Are pleuromutilin antibiotics finally fit for human use? Ann. N. Y. Acad. Sci. 1241 (2011) 71-81.
12. [12]
  [12] W.T. Prince, Z. Ivezic-Schoenfeld, C. Lell, et al., Phase Ⅱ clinical study of BC-3781, a pleuromutilin antibiotic, in treatment of patients with acute bacterial skin and skin structure infections, Antimicrob. Agents Chemother. 57 (2013) 2087-2094.
13. [13]
  [13] Y.S. Lee, J.H. Park, M.H. Kim, S.H. Seo, H.J. Kim, Synthesis of tyrosinase inhibitory kojic acid derivative, Arch. Pharm. 339 (2006) 111-114.
14. [14]
  [14] B.V.S. Reddy, M.R. Reddy, C.H. Madan, K.P. Kumar, M.S. Rao, Indium(Ⅲ) chloride catalyzed three-component coupling reaction: a novel synthesis of 2-substituted aryl(indolyl)kojic acid derivatives as potent antifungal and antibacterial agents, Bioorg. Med. Chem. Lett. 20 (2010) 7507-7511.
15. [15]
  [15] J.M. Bueno, P. Manzano, M.C. García, et al., Potent antimalarial 4-pyridones with improved physico-chemical properties, Bioorg. Med. Chem. Lett. 21 (2011) 5214-5218.
16. [16]
  [16] Y.H. Chen, P.J. Lu, C. Hulme, A.Y. Shaw, Synthesis of kojic acid-derived copperchelating apoptosis inducing agents, Med. Chem. Res. 22 (2013) 995-1003.
17. [17]
  [17] M.F. Brown, M.J. Mitton-Fry, J.T. Arcari, et al., Pyridone-conjugated monobactam antibiotics with Gram-negative activity, J. Med. Chem. 56 (2013) 5541-5552.
18. [18]
  [18] CLSI, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard M07-A9, 9th ed., Clinical and Laboratory Standards Institute, Wayne, 2012.
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