Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis
Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisph...
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| Autor*in: |
Hassan, A. M. A. [verfasserIn] El-Hussieny, Marwa [verfasserIn] El-Sayed, Naglaa F. [verfasserIn] Fouad, Marwa A. [verfasserIn] Ewies, Ewies F. [verfasserIn] Ezzat, Manal Abdel Fattah [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2024 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| Übergeordnetes Werk: |
Enthalten in: Medicinal chemistry research - Springer US, 1991, 33(2024), 7 vom: 05. Juni, Seite 1167-1177 |
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| Übergeordnetes Werk: |
volume:33 ; year:2024 ; number:7 ; day:05 ; month:06 ; pages:1167-1177 |
| Links: |
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| DOI / URN: |
10.1007/s00044-024-03242-y |
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| Katalog-ID: |
SPR056674236 |
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| 520 | |a Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. | ||
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| 650 | 4 | |a Osteoclastogenesis |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a Farnesyl pyrophosphate synthase |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Ewies, Ewies F. |e verfasserin |0 (orcid)0000-0002-4832-5766 |4 aut | |
| 700 | 1 | |a Ezzat, Manal Abdel Fattah |e verfasserin |4 aut | |
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10.1007/s00044-024-03242-y doi (DE-627)SPR056674236 (SPR)s00044-024-03242-y-e DE-627 ger DE-627 rakwb eng 540 610 VZ PHARM DE-84 fid 44.42 bkl 42.13 bkl 35.71 bkl Hassan, A. M. A. verfasserin aut Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. Osteoporosis (dpeaa)DE-He213 Osteoclastogenesis (dpeaa)DE-He213 Bisphosphonates (dpeaa)DE-He213 Farnesyl pyrophosphate synthase (dpeaa)DE-He213 El-Hussieny, Marwa verfasserin aut El-Sayed, Naglaa F. verfasserin aut Fouad, Marwa A. verfasserin aut Ewies, Ewies F. verfasserin (orcid)0000-0002-4832-5766 aut Ezzat, Manal Abdel Fattah verfasserin aut Enthalten in Medicinal chemistry research Springer US, 1991 33(2024), 7 vom: 05. Juni, Seite 1167-1177 (DE-627)490223427 (DE-600)2191978-1 1554-8120 nnns volume:33 year:2024 number:7 day:05 month:06 pages:1167-1177 https://dx.doi.org/10.1007/s00044-024-03242-y X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.42 VZ 42.13 VZ 35.71 VZ AR 33 2024 7 05 06 1167-1177 |
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10.1007/s00044-024-03242-y doi (DE-627)SPR056674236 (SPR)s00044-024-03242-y-e DE-627 ger DE-627 rakwb eng 540 610 VZ PHARM DE-84 fid 44.42 bkl 42.13 bkl 35.71 bkl Hassan, A. M. A. verfasserin aut Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. Osteoporosis (dpeaa)DE-He213 Osteoclastogenesis (dpeaa)DE-He213 Bisphosphonates (dpeaa)DE-He213 Farnesyl pyrophosphate synthase (dpeaa)DE-He213 El-Hussieny, Marwa verfasserin aut El-Sayed, Naglaa F. verfasserin aut Fouad, Marwa A. verfasserin aut Ewies, Ewies F. verfasserin (orcid)0000-0002-4832-5766 aut Ezzat, Manal Abdel Fattah verfasserin aut Enthalten in Medicinal chemistry research Springer US, 1991 33(2024), 7 vom: 05. Juni, Seite 1167-1177 (DE-627)490223427 (DE-600)2191978-1 1554-8120 nnns volume:33 year:2024 number:7 day:05 month:06 pages:1167-1177 https://dx.doi.org/10.1007/s00044-024-03242-y X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.42 VZ 42.13 VZ 35.71 VZ AR 33 2024 7 05 06 1167-1177 |
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10.1007/s00044-024-03242-y doi (DE-627)SPR056674236 (SPR)s00044-024-03242-y-e DE-627 ger DE-627 rakwb eng 540 610 VZ PHARM DE-84 fid 44.42 bkl 42.13 bkl 35.71 bkl Hassan, A. M. A. verfasserin aut Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. Osteoporosis (dpeaa)DE-He213 Osteoclastogenesis (dpeaa)DE-He213 Bisphosphonates (dpeaa)DE-He213 Farnesyl pyrophosphate synthase (dpeaa)DE-He213 El-Hussieny, Marwa verfasserin aut El-Sayed, Naglaa F. verfasserin aut Fouad, Marwa A. verfasserin aut Ewies, Ewies F. verfasserin (orcid)0000-0002-4832-5766 aut Ezzat, Manal Abdel Fattah verfasserin aut Enthalten in Medicinal chemistry research Springer US, 1991 33(2024), 7 vom: 05. Juni, Seite 1167-1177 (DE-627)490223427 (DE-600)2191978-1 1554-8120 nnns volume:33 year:2024 number:7 day:05 month:06 pages:1167-1177 https://dx.doi.org/10.1007/s00044-024-03242-y X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.42 VZ 42.13 VZ 35.71 VZ AR 33 2024 7 05 06 1167-1177 |
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10.1007/s00044-024-03242-y doi (DE-627)SPR056674236 (SPR)s00044-024-03242-y-e DE-627 ger DE-627 rakwb eng 540 610 VZ PHARM DE-84 fid 44.42 bkl 42.13 bkl 35.71 bkl Hassan, A. M. A. verfasserin aut Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. Osteoporosis (dpeaa)DE-He213 Osteoclastogenesis (dpeaa)DE-He213 Bisphosphonates (dpeaa)DE-He213 Farnesyl pyrophosphate synthase (dpeaa)DE-He213 El-Hussieny, Marwa verfasserin aut El-Sayed, Naglaa F. verfasserin aut Fouad, Marwa A. verfasserin aut Ewies, Ewies F. verfasserin (orcid)0000-0002-4832-5766 aut Ezzat, Manal Abdel Fattah verfasserin aut Enthalten in Medicinal chemistry research Springer US, 1991 33(2024), 7 vom: 05. Juni, Seite 1167-1177 (DE-627)490223427 (DE-600)2191978-1 1554-8120 nnns volume:33 year:2024 number:7 day:05 month:06 pages:1167-1177 https://dx.doi.org/10.1007/s00044-024-03242-y X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.42 VZ 42.13 VZ 35.71 VZ AR 33 2024 7 05 06 1167-1177 |
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10.1007/s00044-024-03242-y doi (DE-627)SPR056674236 (SPR)s00044-024-03242-y-e DE-627 ger DE-627 rakwb eng 540 610 VZ PHARM DE-84 fid 44.42 bkl 42.13 bkl 35.71 bkl Hassan, A. M. A. verfasserin aut Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. Osteoporosis (dpeaa)DE-He213 Osteoclastogenesis (dpeaa)DE-He213 Bisphosphonates (dpeaa)DE-He213 Farnesyl pyrophosphate synthase (dpeaa)DE-He213 El-Hussieny, Marwa verfasserin aut El-Sayed, Naglaa F. verfasserin aut Fouad, Marwa A. verfasserin aut Ewies, Ewies F. verfasserin (orcid)0000-0002-4832-5766 aut Ezzat, Manal Abdel Fattah verfasserin aut Enthalten in Medicinal chemistry research Springer US, 1991 33(2024), 7 vom: 05. Juni, Seite 1167-1177 (DE-627)490223427 (DE-600)2191978-1 1554-8120 nnns volume:33 year:2024 number:7 day:05 month:06 pages:1167-1177 https://dx.doi.org/10.1007/s00044-024-03242-y X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.42 VZ 42.13 VZ 35.71 VZ AR 33 2024 7 05 06 1167-1177 |
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Hassan, A. M. A. @@aut@@ El-Hussieny, Marwa @@aut@@ El-Sayed, Naglaa F. @@aut@@ Fouad, Marwa A. @@aut@@ Ewies, Ewies F. @@aut@@ Ezzat, Manal Abdel Fattah @@aut@@ |
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A.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. 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Hassan, A. M. A. |
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Hassan, A. M. A. ddc 540 fid PHARM bkl 44.42 bkl 42.13 bkl 35.71 misc Osteoporosis misc Osteoclastogenesis misc Bisphosphonates misc Farnesyl pyrophosphate synthase Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis |
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540 610 VZ PHARM DE-84 fid 44.42 bkl 42.13 bkl 35.71 bkl Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis Osteoporosis (dpeaa)DE-He213 Osteoclastogenesis (dpeaa)DE-He213 Bisphosphonates (dpeaa)DE-He213 Farnesyl pyrophosphate synthase (dpeaa)DE-He213 |
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ddc 540 fid PHARM bkl 44.42 bkl 42.13 bkl 35.71 misc Osteoporosis misc Osteoclastogenesis misc Bisphosphonates misc Farnesyl pyrophosphate synthase |
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ddc 540 fid PHARM bkl 44.42 bkl 42.13 bkl 35.71 misc Osteoporosis misc Osteoclastogenesis misc Bisphosphonates misc Farnesyl pyrophosphate synthase |
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Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis |
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Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis |
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Hassan, A. M. A. |
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Hassan, A. M. A. El-Hussieny, Marwa El-Sayed, Naglaa F. Fouad, Marwa A. Ewies, Ewies F. Ezzat, Manal Abdel Fattah |
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synthesis and characterization of new tetrakisphosphonic acid derivatives as fpps inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis |
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Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis |
| abstract |
Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstractGer |
Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstract_unstemmed |
Abstract Numerous bone illnesses, including osteoporosis, are brought on by abnormal osteoclast differentiation. The identification of effective strategies for preventing osteoporosis involves focusing on the production and activation of osteoclasts. Herein, we synthesized a new series of tetrakisphosphonic acid derivatives and assessed their farnesyl pyrophosphate synthase inhibitory activity (FPPS) and anti-osteoclastogenic properties in vitro using the MTT assay and the Tartrate-Resistant Acid Phosphatase (TRAP) staining test. Among the synthesized novel tetrakisphosphonic acid derivatives, the unsubstituted benzylidene derivative 2a and the 2-brominated benzylidene derivative 2g exhibited the most promising bioactivity on the FPPS. All the synthesized compounds were proven to have the capacity to decrease the osteoclastogenesis process. Furthermore, both compounds 2a and 2g displayed the highest antiosteoclastogenic activity when compared to the reference compound, zoledronate. Molecular docking investigations revealed the probable interaction patterns between the potent derivatives 2a and 2g in the hFPPS binding pocket. The results of this investigation indicated that these novel compounds might be useful as FPPS-targeting and antiosteoclastogenic medications. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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Synthesis and characterization of new tetrakisphosphonic acid derivatives as FPPS inhibitors and evaluation of their anti-osteoclastogenic potential for prevention of osteoporosis |
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| score |
7.400448 |