Identification and Synthesis of DDI-6, a Quinolinol Analog Capable of Activating Both <i>Caenorhabditis elegans</i> and Mouse Spermatozoa
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- Karuo Yukiko
- Faculty of Pharmaceutical Sciences, Setsunan University
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- Shiraki Riona
- Department of Life Science, Faculty of Science and Engineering, Setsunan University
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- Yoshida Ayaka
- Department of Life Science, Faculty of Science and Engineering, Setsunan University
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- Tsunokawa Ryo
- Faculty of Pharmaceutical Sciences, Setsunan University
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- Nakahara-Yamada Mayuko
- Department of Life Science, Faculty of Science and Engineering, Setsunan University
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- Tarui Atsushi
- Faculty of Pharmaceutical Sciences, Setsunan University
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- Sato Kazuyuki
- Faculty of Pharmaceutical Sciences, Setsunan University
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- Kawai Kentaro
- Faculty of Pharmaceutical Sciences, Setsunan University
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- Omote Masaaki
- Faculty of Pharmaceutical Sciences, Setsunan University
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- Nishimura Hitoshi
- Department of Life Science, Faculty of Science and Engineering, Setsunan University
Bibliographic Information
- Other Title
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- Identification and Synthesis of DDI-6, a Quinolinol Analog Capable of Activating Both Caenorhabditis elegans and Mouse Spermatozoa
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Abstract
<p>Sperm activation is an essential process by which the male gametes become capable of fertilization. Because the process in Caenorhabditis elegans is readily reproducible in vitro, this organism serves as an excellent model to investigate it. C. elegans sperm activation in vivo occurs during spermiogenesis. Membranous organelles (MOs) contained within spermatids fuse with the plasma membrane, resulting in extracellular release of their contents and relocation of some proteins indispensable for fertilization from the MO membrane onto the sperm surface. Intriguingly, these cytological alternations are exhibited similarly in mouse spermatozoa during the acrosome reaction, which also represents a form of sperm activation, prompting us to hypothesize that C. elegans and mice share a common mechanism for sperm activation. To explore this, we first screened a chemical library to identify compounds that activate C. elegans spermatozoa. Because a quinolinol analog named DDI-6 seemed to be a candidate sperm activator, we synthesized it to use for further analyses. This involved direct dechlorination and hydrogenolysis of commercially available 5-chloro-8-quinolinol, both of which are key steps to yield 1,2,3,4-tetrahydro-8-quinolinol, and we subsequently introduced the sulfonamide group to the compound. When C. elegans spermatids were stimulated with solvent alone or the newly synthesized DDI-6, approx. 3% and approx. 28% of spermatids became MO-fused spermatozoa, respectively. Moreover, DDI-6 triggered the acrosome reaction in approx. 20% of mouse spermatozoa, while approx. 12% became acrosome-reacted after mock stimulation. Thus, DDI-6 serves as a moderately effective activator for both C. elegans and mouse spermatozoa.</p>
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 69 (6), 557-563, 2021-06-01
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390851165524113152
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- NII Article ID
- 130008046497
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- NII Book ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 031478296
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- PubMed
- 34078802
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed