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Planta Med 2017; 83(09): 805-811
DOI: 10.1055/s-0043-100382
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antichlamydial Dimeric Indole Derivatives from Marine Actinomycete Rubrobacter radiotolerans

Jian Lin Li   *
1   School of Pharmacy, Nantong University, Nantong, China
,
Dandan Chen   *
1   School of Pharmacy, Nantong University, Nantong, China
2   Department of Pharmacy, The Second Peopleʼs Hospital of Nantong, Nantong, China
,
Lei Huang
1   School of Pharmacy, Nantong University, Nantong, China
,
Min Ni
1   School of Pharmacy, Nantong University, Nantong, China
,
Yu Zhao
1   School of Pharmacy, Nantong University, Nantong, China
,
Huizhou Fan
3   Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, USA
,
Xiaofeng Bao
1   School of Pharmacy, Nantong University, Nantong, China
› Author Affiliations
Further Information

Publication History

received 26 September 2016
revised 19 December 2016

accepted 29 December 2016

Publication Date:
17 January 2017 (online)

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Abstract

Chlamydiae are widely distributed pathogens of human populations, which can lead to serious reproductive and other health problems. In our search for novel antichlamydial metabolites from marine derived-microorganisms, one new (1) and two known (2, 3) dimeric indole derivatives were isolated from the sponge-derived actinomycete Rubrobacter radiotolerans. The chemical structures of these metabolites were elucidated by NMR spectroscopic data as well as CD calculations. All three metabolites suppressed chlamydial growth in a concentration-dependent manner. Among them, compound 1 exhibited the most effective antichlamydial activity with IC50 values of 46.6 ~ 96.4 µM in the production of infectious progeny. Compounds appeared to target the mid-stage of the chlamydial developmental cycle by interfering with reticular body replication, but not directly inactivating the infectious elementary body.

Key words

Chlamydia - dimeric indole - sponges - actinomycete - Rubrobacter radiotolerans - antichlamydial

* These two authors contributed equally to this work.


Supporting Information

1H, 13C, and 2D NMR data of compound 1 and concentration-response curves for generating IC50 values of the three compounds on each Chlamydia are available as Supporting Information.

 

  • References

  • 1 Abdelrahman YM, Belland RJ. The chlamydial developmental cycle. FEMS Microbiol Rev 2005; 29: 949-959
    CrossrefPubMedGoogle Scholar
  • 2 Stephens RS, Myers G, Eppinger M, Bavoil PM. Divergence without difference: phylogenetics and taxonomy of Chlamydia resolved. FEMS Immunol Med Microbiol 2009; 55: 115-119
    CrossrefPubMedGoogle Scholar
  • 3 Potroz MG, Cho NJ. Natural products for the treatment of trachoma and Chlamydia trachomatis . Molecules 2015; 20: 4180-4203
    CrossrefPubMedGoogle Scholar
  • 4 Fan H. Blindness-causing trachomatous trichiasis biomarkers sighted. Invest Ophthalmol Vis Sci 2012; 53: 2560
    CrossrefPubMedGoogle Scholar
  • 5 Belland RJ, Ouellette SP, Gieffers J, Byrne GI. Chlamydia pneumoniae and atherosclerosis. Cell Microbiol 2004; 6: 117-127
    CrossrefPubMedGoogle Scholar
  • 6 Grau AJ, Urbanek C, Palm F. Common infections and the risk of stroke. Nat Rev Neurol 2010; 6: 681-694
    PubMedGoogle Scholar
  • 7 Balin BJ, Little CS, Hammond CJ, Appelt DM, Whittum-Hudson JA, Gerard HC, Hudson AP. Chlamydophila pneumoniae and the etiology of late-onset Alzheimerʼs disease. J Alzheimers Dis 2008; 13: 371-380
    CrossrefPubMedGoogle Scholar
  • 8 Hybiske K, Stephens RS. Mechanisms of Chlamydia trachomatis entry into nonphagocytic cells. Infect Immun 2007; 75: 3925-3934
    CrossrefPubMedGoogle Scholar
  • 9 Hybiske K, Stephens RS. Mechanisms of host cell exit by the intracellular bacterium Chlamydia . Proc Natl Acad Sci U S A 2007; 104: 11430-11435
    CrossrefPubMedGoogle Scholar
  • 10 Beeckman DS, De Puysseleyr L, De Puysseleyr K, Vanrompay D. Chlamydial biology and its associated virulence blockers. Crit Rev Microbiol 2014; 40: 313-328
    CrossrefPubMedGoogle Scholar
  • 11 Sandoz KM, Rockey DD. Antibiotic resistance in Chlamydiae. Future Microbiol 2010; 5: 1427-1442
    CrossrefPubMedGoogle Scholar
  • 12 Workowski KA, Levine WC, Wasserheit JN. Centers for Disease Control and Prevention, Atlanta, Georgia. U.S. Centers for Disease Control and Prevention guidelines for the treatment of sexually transmitted diseases: an opportunity to unify clinical and public health practice. Ann Intern Med 2002; 137: 255-262
    CrossrefPubMedGoogle Scholar
  • 13 Workowski KA. Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. Clin Infect Dis 2015; 61 (Suppl. 08) S759-S762
    CrossrefPubMedGoogle Scholar
  • 14 Hogan RJ, Mathews SA, Mukhopadhyay S, Summersgill JT, Timms P. Chlamydial persistence: beyond the biphasic paradigm. Infect Immun 2004; 72: 1843-1855
    CrossrefPubMedGoogle Scholar
  • 15 Yokoi S, Yasuda M, Ito S, Takahashi Y, Ishihara S, Deguchi T, Maeda S, Kubota Y, Tamaki M, Fukushi H. Uncommon occurrence of fluoroquinolone resistance-associated alterations in GyrA and ParC in clinical strains of Chlamydia trachomatis . J Infect Chemother 2004; 10: 262-267
    CrossrefPubMedGoogle Scholar
  • 16 Khachatryan AR, Besser TE, Call DR. The streptomycin-sulfadiazine-tetracycline antimicrobial resistance element of calf-adapted Escherichia coli is widely distributed among isolates from Washington state cattle. Appl Environ Microbiol 2008; 74: 391-395
    CrossrefPubMedGoogle Scholar
  • 17 Di Francesco A, Donati M, Rossi M, Pignanelli S, Shurdhi A, Baldelli R, Cevenini R. Tetracycline-resistant Chlamydia suis isolates in Italy. Vet Rec 2008; 163: 251-252
    CrossrefPubMedGoogle Scholar
  • 18 Binet R, Bowlin AK, Maurelli AT, Rank RG. Impact of azithromycin resistance mutations on the virulence and fitness of Chlamydia caviae in guinea pigs. Antimicrob Agents Chemother 2010; 54: 1094-1101
    CrossrefPubMedGoogle Scholar
  • 19 Igietseme JU, Eko FO, Black CM. Chlamydia vaccines: recent developments and the role of adjuvants in future formulations. Expert Rev Vaccines 2011; 10: 1585-1596
    CrossrefPubMedGoogle Scholar
  • 20 Mabey DC, Hu V, Bailey RL, Burton MJ, Holland MJ. Towards a safe and effective chlamydial vaccine: lessons from the eye. Vaccine 2014; 32: 1572-1578
    CrossrefPubMedGoogle Scholar
  • 21 Bao X, Gylfe A, Sturdevant GL, Gong Z, Xu S, Caldwell HD, Elofsson M, Fan H. Benzylidene acylhydrazides inhibit chlamydial growth in a type III secretion- and iron chelation-independent manner. J Bacteriol 2014; 196: 2989-3001
    CrossrefPubMedGoogle Scholar
  • 22 Good JA, Silver J, Nunez-Otero C, Bahnan W, Krishnan KS, Salin O, Engstrom P, Svensson R, Artursson P, Gylfe A, Bergstrom S, Almqvist F. Thiazolino 2-pyridone amide inhibitors of Chlamydia trachomatis infectivity. J Med Chem 2016; 59: 2094-2108
    CrossrefPubMedGoogle Scholar
  • 23 Hanski L, Ausbacher D, Tiirola TM, Strom MB, Vuorela PM. Amphipathic beta2, 2-amino acid derivatives suppress infectivity and disrupt the intracellular replication cycle of Chlamydia pneumoniae . PLoS One 2016; 11: e0157306
    CrossrefPubMedGoogle Scholar
  • 24 Horan AC, Shearer MC, Hedge V, Beyazova ML, Brodsky BC, King A, Berrie R, Cardaci K, Nimeck M. A family of novel macrocyclic lactones, the saccharocarcins produced by Saccharothrix aerocolonigenes subsp. antibiotica. I. Taxonomy, fermentation, isolation and biological properties. J Antibiot (Tokyo) 1997; 50: 119-125
    CrossrefPubMedGoogle Scholar
  • 25 Salin O, Alakurtti S, Pohjala L, Siiskonen A, Maass V, Maass M, Yli-Kauhaluoma J, Vuorela P. Inhibitory effect of the natural product betulin and its derivatives against the intracellular bacterium Chlamydia pneumoniae . Biochem Pharmacol 2010; 80: 1141-1151
    CrossrefPubMedGoogle Scholar
  • 26 Abdelmohsen UR, Cheng C, Reimer A, Kozjak-Pavlovic V, Ibrahim AK, Rudel T, Hentschel U, Edrada-Ebel R, Ahmed SA. Antichlamydial sterol from the red sea sponge Callyspongia aff. implexa . Planta Med 2015; 81: 382-387
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Mondol MA, Kim JH, Lee MA, Tareq FS, Lee HS, Lee YJ, Shin HJ. Ieodomycins A–D, antimicrobial fatty acids from a marine Bacillus sp. J Nat Prod 2011; 74: 1606-1612
    CrossrefPubMedGoogle Scholar
  • 28 Li JL, Huang L, Liu J, Song Y, Gao J, Jung JH, Liu Y, Chen G. Acetylcholinesterase inhibitory dimeric indole derivatives from the marine actinomycetes Rubrobacter radiotolerans . Fitoterapia 2015; 102: 203-207
    CrossrefPubMedGoogle Scholar