Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception
Motile cilia play essential roles in various physiological processes including fluid flow generation and sperm motility. In this study, we identified 1,3-diphenyl-6-(4-phenylpiperazin-1-yl)benzo[<i>e</i>][1,2,4]triazin-7(1<i>H</i>)-one as a potent and reversible modulator of...
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2025-05-01
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| author | Maria Chatzifrangkeskou Alexandra Perdiou Revekka Kreouzou Georgia A. Zissimou Dragos F. Flesariu Panayiotis A. Koutentis Paris A. Skourides |
| author_facet | Maria Chatzifrangkeskou Alexandra Perdiou Revekka Kreouzou Georgia A. Zissimou Dragos F. Flesariu Panayiotis A. Koutentis Paris A. Skourides |
| author_sort | Maria Chatzifrangkeskou |
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| description | Motile cilia play essential roles in various physiological processes including fluid flow generation and sperm motility. In this study, we identified 1,3-diphenyl-6-(4-phenylpiperazin-1-yl)benzo[<i>e</i>][1,2,4]triazin-7(1<i>H</i>)-one as a potent and reversible modulator of ciliary function using the <i>Xenopus laevis</i> model. This benzotriazinone derivative inhibits ciliary-driven fluid flow by inducing cilia detachment without causing toxicity in developing embryos. Unlike traditional deciliation agents that rely on calcium signaling, this compound induces cilia loss through a shear stress-driven mechanism at the transition zone, without disrupting tissue morphology or the apical actin network. Importantly, it also induces flagellar loss and impairs sperm motility at picomolar concentrations. Our findings highlight the potential of this 6-(4-phenylpiperazin-1-yl)-substituted benzotriazinone as a non-hormonal male contraceptive and underscore a novel mechanism of cilia modulation that may have broader implications for the treatment of cilia-related disorders. |
| format | Article |
| id | doaj-art-bf022b0d3c7e418594bccbc893c5318f |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Cells |
| spelling | doaj-art-bf022b0d3c7e418594bccbc893c5318f2025-08-20T01:56:17ZengMDPI AGCells2073-44092025-05-01141068810.3390/cells14100688Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male ContraceptionMaria Chatzifrangkeskou0Alexandra Perdiou1Revekka Kreouzou2Georgia A. Zissimou3Dragos F. Flesariu4Panayiotis A. Koutentis5Paris A. Skourides6Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusDepartment of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusDepartment of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusDepartment of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusDepartment of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusDepartment of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusDepartment of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusMotile cilia play essential roles in various physiological processes including fluid flow generation and sperm motility. In this study, we identified 1,3-diphenyl-6-(4-phenylpiperazin-1-yl)benzo[<i>e</i>][1,2,4]triazin-7(1<i>H</i>)-one as a potent and reversible modulator of ciliary function using the <i>Xenopus laevis</i> model. This benzotriazinone derivative inhibits ciliary-driven fluid flow by inducing cilia detachment without causing toxicity in developing embryos. Unlike traditional deciliation agents that rely on calcium signaling, this compound induces cilia loss through a shear stress-driven mechanism at the transition zone, without disrupting tissue morphology or the apical actin network. Importantly, it also induces flagellar loss and impairs sperm motility at picomolar concentrations. Our findings highlight the potential of this 6-(4-phenylpiperazin-1-yl)-substituted benzotriazinone as a non-hormonal male contraceptive and underscore a novel mechanism of cilia modulation that may have broader implications for the treatment of cilia-related disorders.https://www.mdpi.com/2073-4409/14/10/688motile ciliadeciliation<i>Xenopus laevis</i>transition zone |
| spellingShingle | Maria Chatzifrangkeskou Alexandra Perdiou Revekka Kreouzou Georgia A. Zissimou Dragos F. Flesariu Panayiotis A. Koutentis Paris A. Skourides Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception Cells motile cilia deciliation <i>Xenopus laevis</i> transition zone |
| title | Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception |
| title_full | Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception |
| title_fullStr | Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception |
| title_full_unstemmed | Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception |
| title_short | Reversible Modulation of Motile Cilia by a Benzo[<i>e</i>][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception |
| title_sort | reversible modulation of motile cilia by a benzo i e i 1 2 4 triazinone a potential non hormonal approach to male contraception |
| topic | motile cilia deciliation <i>Xenopus laevis</i> transition zone |
| url | https://www.mdpi.com/2073-4409/14/10/688 |
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