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Aspects for development of novel antibacterial medicines using a vitamin D3 decomposition product in Helicobacter pylori infection

The Journal of Antibiotics volume 76, pages 665–672 (2023)Cite this article

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Abstract

A previous study by our group demonstrated that a vitamin D3 decomposition product (VDP1) acts as the selective bactericidal substance on Helicobacter pylori. VDP1 is an indene compound modified with a carbonyl and an alkyl. The alkyl of VDP1 turned out to be a mandatory structure to exert effective bactericidal action on H. pylori. Meanwhile, it still remains to be clarified as to how influence the alteration of the carbonyl in VDP1 has on the anti-H. pylori activity. In this study, we synthesized novel VDP1 derivatives that replaced the carbonyl of VDP1 by various functional groups and investigated the antibacterial action of the VDP1 derivatives on H. pylori. VDP1 derivatives retaining either a hydroxy (VD3-1) or an acetic ester (VD3-3) exhibited more effective bactericidal action to H. pylori than VDP1. The replacement of the carbonyl of VDP1 by either an allyl acetate (VD3-2) or an acrylic acid (VD3-5) provided almost no change to the anti-H. pylori activity. Apart from this, an isomer of VDP1 (VD3-4) slightly improved anti-H. pylori activity of VDP1. Meanwhile, the replacement of the carbonyl of VDP1 by a methyl acrylate (VD3-6) attenuated the anti-H. pylori activity. As with VDP1, its derivatives also were suggested to exert the anti-H. pylori action through the interaction with myristic acid side chains of dimyristoyl-phosphatidylethanolamine, a characteristic membrane lipid constituent of this pathogen. These results indicate that it is capable of developing specific antibacterial medicines for H. pylori targeting the biomembranal dimyristoyl-phosphatidylethanolamine using VDP1 as the fundamental structure.

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Funding

This work was supported by a Grant-in-Aid from Adaptable and Seamless Technology Transfer Program through Target-driven R&D (A-STEP), JSPS KAKENHI (Grant Number 23K04952), and JKA promotion funds from KEIRIN RACE.

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Author notes

  1. These authors contributed equally: Kiyofumi Wanibuchi, Kouichi Hosoda, Avarzed Amgalanbaatar.

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Yokohama University of Pharmacy, 601, Matano-cho, Totsuka-ku, Yokohama-shi, Kanagawa, 245-0066, Japan

    Kiyofumi Wanibuchi, Masato Ihara, Motoki Takezawa, Yuki Sakai & Mitsuru Shoji

  2. Nikon Cell Innovation Co., Ltd., 2-4-10, Shinsuna, Koto-ku, Tokyo, 136-0075, Japan

    Kouichi Hosoda

  3. Department of Graduate Education, Graduate School, Mongolian National University of Medical Sciences, 14210, Zoing street, Sukhbaatar District, Ulaanbaatar, 14210, Mongolia

    Avarzed Amgalanbaatar

  4. Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan

    Hisashi Masui

  5. Department of Microbiology, School of Medicine, Kitasato University, 1-15-1, Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, 252-0374, Japan

    Shunji Hayashi

  6. Public Health Center of Uki, Kumamoto Prefecture Office, 400-1, Kugu, Matsubase-machi, Uki-shi, Kumamoto, 869-0532, Japan

    Hirofumi Shimomura

Authors
  1. Kiyofumi Wanibuchi
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  2. Kouichi Hosoda
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  3. Avarzed Amgalanbaatar
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  5. Motoki Takezawa
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  6. Yuki Sakai
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  9. Shunji Hayashi
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  10. Hirofumi Shimomura
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Correspondence to Hirofumi Shimomura.

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Wanibuchi, K., Hosoda, K., Amgalanbaatar, A. et al. Aspects for development of novel antibacterial medicines using a vitamin D3 decomposition product in Helicobacter pylori infection. J Antibiot 76, 665–672 (2023). https://doi.org/10.1038/s41429-023-00651-w

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