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Identification and characterization of a vitamin D₃ decomposition product bactericidal against Helicobacter pylori.

Hosoda K, Shimomura H, Wanibuchi K, Masui H, Amgalanbaatar A, Hayashi S, Takahashi T, Hirai Y - Sci Rep (2015)

Bottom Line: A unique dimyristoyl phosphatidylethanolamine in the membrane lipid compositions contributed to the interaction of VDP1 with H. pylori cells.In both (1)H and (13)C NMR analyses, the spectra patterns of VDP1 corresponded with those of Grundmann's ketone.These results suggest that VDP1 (or Grundmann's ketone-type indene compound) may become a fundamental structure for the development of new antibacterial substances with selective bactericidal action against H. pylori.

View Article: PubMed Central - PubMed

Affiliation: Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi. 329-0498, Japan.

ABSTRACT
This study demonstrated that the vitamin D₃ decomposition product VDP1 exerts an antibacterial action against Helicobacter pylori but not against other bacteria. Treatment with VDP1 induced a collapse of cell membrane structures of H. pylori and ultimately lysed the bacterial cells. A unique dimyristoyl phosphatidylethanolamine in the membrane lipid compositions contributed to the interaction of VDP1 with H. pylori cells. In separate experiments, VDP1 had no influence on the viability of the human cancer cell lines MKN45 and T47D and lacked any vitamin D₃-like hormonal action against the latter. In both (1)H and (13)C NMR analyses, the spectra patterns of VDP1 corresponded with those of Grundmann's ketone. These results suggest that VDP1 (or Grundmann's ketone-type indene compound) may become a fundamental structure for the development of new antibacterial substances with selective bactericidal action against H. pylori.

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Anti-H. pylori activity of synthetic VDP1.(a) Chemical structure of VDP1. (b) The minimum inhibitory concentrations (MICs) of VDP1 and 1α,25-dihydroxyvitamin D3 (1,25D3) for the FC-retaining H. pylori strain NCTC 11638. (c) Eight bacterial species (107 CFU/ml), including five strains of H. pylori, were incubated for 24 h in a broth (1.5 ml) containing various concentrations of VDP1 in addition to 30 μM FC. After the incubation, the CFUs were counted to determine the minimum bactericidal concentrations (MBCs) that completely eradicate the 106 CFU of bacteria. Seven bacterial species were used in the experiment: S. aureus, E. coli, Salmonella, K. pneumoniae, P. mirabilis, S. marcescens and P. aeruginosa. (d) The FC-retaining H. pylori strain NCTC 11638 was incubated for 0.5 to 2 h in the presence of a 2 μg/ml concentration of VDP1, amoxicillin (AX) or kanamycin (KM) in a broth (1.5 ml) containing 30 μM FC, and the CFUs were counted. The mean CFU ± SD per ml was calculated from three independent experiments.
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f6: Anti-H. pylori activity of synthetic VDP1.(a) Chemical structure of VDP1. (b) The minimum inhibitory concentrations (MICs) of VDP1 and 1α,25-dihydroxyvitamin D3 (1,25D3) for the FC-retaining H. pylori strain NCTC 11638. (c) Eight bacterial species (107 CFU/ml), including five strains of H. pylori, were incubated for 24 h in a broth (1.5 ml) containing various concentrations of VDP1 in addition to 30 μM FC. After the incubation, the CFUs were counted to determine the minimum bactericidal concentrations (MBCs) that completely eradicate the 106 CFU of bacteria. Seven bacterial species were used in the experiment: S. aureus, E. coli, Salmonella, K. pneumoniae, P. mirabilis, S. marcescens and P. aeruginosa. (d) The FC-retaining H. pylori strain NCTC 11638 was incubated for 0.5 to 2 h in the presence of a 2 μg/ml concentration of VDP1, amoxicillin (AX) or kanamycin (KM) in a broth (1.5 ml) containing 30 μM FC, and the CFUs were counted. The mean CFU ± SD per ml was calculated from three independent experiments.

Mentions: The analysis of both 1H-NMR and 13C-NMR identified VDP1 with Grundmann's ketone, (1R,3aR,7aR)-1-[(1R)-1,5-dimethylhexyl]octahydro-7a-methyl-4H-inden-4-one, which was obtained via the oxidative reaction of vitamin D3 catalyzed by ruthenium (Fig. 6a). The NMR spectra of the purified VDP1 were detected as follows: 1H NMR (500 MHz, CDCl3) δ 2.44 (dd, J = 11.8, 7 Hz, 1H), 2.26 (ddd, J = 14.2, 6.0, 2.0 Hz, 1H), 2.22 (m, 1H), 2.12 (ddd, J = 13.1, 9.6, 2.8 Hz, 1H), 2.00 (m, 1H), 1.90 (m, 2H), 1.72 (m, 1H), 1.52 (m, 3H), 1.42 (m, 2H), 1.34 (m, 2H), 1.30 (m, 1H), 1.14 (m, 3H), 1.04 (m, 1H), 0.95 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.64 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 212.5, 62.2, 56.9, 50.1, 41.2, 39.6, 39.1, 36.2, 35.7, 28.1, 27.7, 24.2, 24.0, 23.0, 22.7, 19.2, 18.9, 12.6. Meanwhile, the NMR spectra of the synthesized VDP1 were detected as follows: 1H NMR (500 MHz, CDCl3) δ 2.45 (dd, J = 11.8, 7 Hz, 1H), 2.27 (ddd, J = 14.2, 6.0, 2.0 Hz, 1H), 2.22 (m, 1H), 2.12 (ddd, J = 13.1, 9.6, 2.8 Hz, 1H), 2.00 (m, 1H), 1.90 (m, 2H), 1.72 (m, 1H), 1.57 (m, 1H), 1.52 (m, 2H), 1.42 (m, 1H), 1.39 (m, 1H), 1.34 (m, 2H), 1.30 (m, 1H), 1.14 (m, 3H), 1.04 (m, 1H), 0.95 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.64 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 212.4, 62.2, 56.9, 50.1, 41.1, 39.6, 39.1, 36.1, 35.7, 28.1, 27.7, 24.2, 24.0, 23.0, 22.7, 19.2, 18.9, 12.6 (see Supplementary Figs. S1 and S2).


Identification and characterization of a vitamin D₃ decomposition product bactericidal against Helicobacter pylori.

Hosoda K, Shimomura H, Wanibuchi K, Masui H, Amgalanbaatar A, Hayashi S, Takahashi T, Hirai Y - Sci Rep (2015)

Anti-H. pylori activity of synthetic VDP1.(a) Chemical structure of VDP1. (b) The minimum inhibitory concentrations (MICs) of VDP1 and 1α,25-dihydroxyvitamin D3 (1,25D3) for the FC-retaining H. pylori strain NCTC 11638. (c) Eight bacterial species (107 CFU/ml), including five strains of H. pylori, were incubated for 24 h in a broth (1.5 ml) containing various concentrations of VDP1 in addition to 30 μM FC. After the incubation, the CFUs were counted to determine the minimum bactericidal concentrations (MBCs) that completely eradicate the 106 CFU of bacteria. Seven bacterial species were used in the experiment: S. aureus, E. coli, Salmonella, K. pneumoniae, P. mirabilis, S. marcescens and P. aeruginosa. (d) The FC-retaining H. pylori strain NCTC 11638 was incubated for 0.5 to 2 h in the presence of a 2 μg/ml concentration of VDP1, amoxicillin (AX) or kanamycin (KM) in a broth (1.5 ml) containing 30 μM FC, and the CFUs were counted. The mean CFU ± SD per ml was calculated from three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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f6: Anti-H. pylori activity of synthetic VDP1.(a) Chemical structure of VDP1. (b) The minimum inhibitory concentrations (MICs) of VDP1 and 1α,25-dihydroxyvitamin D3 (1,25D3) for the FC-retaining H. pylori strain NCTC 11638. (c) Eight bacterial species (107 CFU/ml), including five strains of H. pylori, were incubated for 24 h in a broth (1.5 ml) containing various concentrations of VDP1 in addition to 30 μM FC. After the incubation, the CFUs were counted to determine the minimum bactericidal concentrations (MBCs) that completely eradicate the 106 CFU of bacteria. Seven bacterial species were used in the experiment: S. aureus, E. coli, Salmonella, K. pneumoniae, P. mirabilis, S. marcescens and P. aeruginosa. (d) The FC-retaining H. pylori strain NCTC 11638 was incubated for 0.5 to 2 h in the presence of a 2 μg/ml concentration of VDP1, amoxicillin (AX) or kanamycin (KM) in a broth (1.5 ml) containing 30 μM FC, and the CFUs were counted. The mean CFU ± SD per ml was calculated from three independent experiments.
Mentions: The analysis of both 1H-NMR and 13C-NMR identified VDP1 with Grundmann's ketone, (1R,3aR,7aR)-1-[(1R)-1,5-dimethylhexyl]octahydro-7a-methyl-4H-inden-4-one, which was obtained via the oxidative reaction of vitamin D3 catalyzed by ruthenium (Fig. 6a). The NMR spectra of the purified VDP1 were detected as follows: 1H NMR (500 MHz, CDCl3) δ 2.44 (dd, J = 11.8, 7 Hz, 1H), 2.26 (ddd, J = 14.2, 6.0, 2.0 Hz, 1H), 2.22 (m, 1H), 2.12 (ddd, J = 13.1, 9.6, 2.8 Hz, 1H), 2.00 (m, 1H), 1.90 (m, 2H), 1.72 (m, 1H), 1.52 (m, 3H), 1.42 (m, 2H), 1.34 (m, 2H), 1.30 (m, 1H), 1.14 (m, 3H), 1.04 (m, 1H), 0.95 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.64 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 212.5, 62.2, 56.9, 50.1, 41.2, 39.6, 39.1, 36.2, 35.7, 28.1, 27.7, 24.2, 24.0, 23.0, 22.7, 19.2, 18.9, 12.6. Meanwhile, the NMR spectra of the synthesized VDP1 were detected as follows: 1H NMR (500 MHz, CDCl3) δ 2.45 (dd, J = 11.8, 7 Hz, 1H), 2.27 (ddd, J = 14.2, 6.0, 2.0 Hz, 1H), 2.22 (m, 1H), 2.12 (ddd, J = 13.1, 9.6, 2.8 Hz, 1H), 2.00 (m, 1H), 1.90 (m, 2H), 1.72 (m, 1H), 1.57 (m, 1H), 1.52 (m, 2H), 1.42 (m, 1H), 1.39 (m, 1H), 1.34 (m, 2H), 1.30 (m, 1H), 1.14 (m, 3H), 1.04 (m, 1H), 0.95 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.87 (d, J = 2.3 Hz, 3H), 0.64 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 212.4, 62.2, 56.9, 50.1, 41.1, 39.6, 39.1, 36.1, 35.7, 28.1, 27.7, 24.2, 24.0, 23.0, 22.7, 19.2, 18.9, 12.6 (see Supplementary Figs. S1 and S2).

Bottom Line: A unique dimyristoyl phosphatidylethanolamine in the membrane lipid compositions contributed to the interaction of VDP1 with H. pylori cells.In both (1)H and (13)C NMR analyses, the spectra patterns of VDP1 corresponded with those of Grundmann's ketone.These results suggest that VDP1 (or Grundmann's ketone-type indene compound) may become a fundamental structure for the development of new antibacterial substances with selective bactericidal action against H. pylori.

View Article: PubMed Central - PubMed

Affiliation: Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi. 329-0498, Japan.

ABSTRACT
This study demonstrated that the vitamin D₃ decomposition product VDP1 exerts an antibacterial action against Helicobacter pylori but not against other bacteria. Treatment with VDP1 induced a collapse of cell membrane structures of H. pylori and ultimately lysed the bacterial cells. A unique dimyristoyl phosphatidylethanolamine in the membrane lipid compositions contributed to the interaction of VDP1 with H. pylori cells. In separate experiments, VDP1 had no influence on the viability of the human cancer cell lines MKN45 and T47D and lacked any vitamin D₃-like hormonal action against the latter. In both (1)H and (13)C NMR analyses, the spectra patterns of VDP1 corresponded with those of Grundmann's ketone. These results suggest that VDP1 (or Grundmann's ketone-type indene compound) may become a fundamental structure for the development of new antibacterial substances with selective bactericidal action against H. pylori.

Show MeSH
Related in: MedlinePlus