Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach

7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reac...
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Autor*in:	Jorge Alberto Valle da Silva [verfasserIn] Eugenie Nepovimova [verfasserIn] Teodorico Castro Ramalho [verfasserIn] Kamil Kuca [verfasserIn] Tanos Celmar Costa França [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	acetylcholinesterase vx molecular modeling nac 7-meota-4-pa

Übergeordnetes Werk:	In: Journal of Enzyme Inhibition and Medicinal Chemistry - Taylor & Francis Group, 2017, 34(2019), 1, Seite 1018-1029
Übergeordnetes Werk:	volume:34 ; year:2019 ; number:1 ; pages:1018-1029

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1080/14756366.2019.1609953

Katalog-ID:	DOAJ077852656

Internformat


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allfields	10.1080/14756366.2019.1609953 doi (DE-627)DOAJ077852656 (DE-599)DOAJ488a172c13024fb4a68ec3b087195a07 DE-627 ger DE-627 rakwb eng RM1-950 Jorge Alberto Valle da Silva verfasserin aut Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction. acetylcholinesterase vx molecular modeling nac 7-meota-4-pa Therapeutics. Pharmacology Eugenie Nepovimova verfasserin aut Teodorico Castro Ramalho verfasserin aut Kamil Kuca verfasserin aut Tanos Celmar Costa França verfasserin aut In Journal of Enzyme Inhibition and Medicinal Chemistry Taylor & Francis Group, 2017 34(2019), 1, Seite 1018-1029 (DE-627)330383906 (DE-600)2049579-1 14756374 nnns volume:34 year:2019 number:1 pages:1018-1029 https://doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/article/488a172c13024fb4a68ec3b087195a07 kostenfrei http://dx.doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/toc/1475-6366 Journal toc kostenfrei https://doaj.org/toc/1475-6374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 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_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 34 2019 1 1018-1029
spelling	10.1080/14756366.2019.1609953 doi (DE-627)DOAJ077852656 (DE-599)DOAJ488a172c13024fb4a68ec3b087195a07 DE-627 ger DE-627 rakwb eng RM1-950 Jorge Alberto Valle da Silva verfasserin aut Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction. acetylcholinesterase vx molecular modeling nac 7-meota-4-pa Therapeutics. Pharmacology Eugenie Nepovimova verfasserin aut Teodorico Castro Ramalho verfasserin aut Kamil Kuca verfasserin aut Tanos Celmar Costa França verfasserin aut In Journal of Enzyme Inhibition and Medicinal Chemistry Taylor & Francis Group, 2017 34(2019), 1, Seite 1018-1029 (DE-627)330383906 (DE-600)2049579-1 14756374 nnns volume:34 year:2019 number:1 pages:1018-1029 https://doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/article/488a172c13024fb4a68ec3b087195a07 kostenfrei http://dx.doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/toc/1475-6366 Journal toc kostenfrei https://doaj.org/toc/1475-6374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 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_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 34 2019 1 1018-1029
allfields_unstemmed	10.1080/14756366.2019.1609953 doi (DE-627)DOAJ077852656 (DE-599)DOAJ488a172c13024fb4a68ec3b087195a07 DE-627 ger DE-627 rakwb eng RM1-950 Jorge Alberto Valle da Silva verfasserin aut Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction. acetylcholinesterase vx molecular modeling nac 7-meota-4-pa Therapeutics. Pharmacology Eugenie Nepovimova verfasserin aut Teodorico Castro Ramalho verfasserin aut Kamil Kuca verfasserin aut Tanos Celmar Costa França verfasserin aut In Journal of Enzyme Inhibition and Medicinal Chemistry Taylor & Francis Group, 2017 34(2019), 1, Seite 1018-1029 (DE-627)330383906 (DE-600)2049579-1 14756374 nnns volume:34 year:2019 number:1 pages:1018-1029 https://doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/article/488a172c13024fb4a68ec3b087195a07 kostenfrei http://dx.doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/toc/1475-6366 Journal toc kostenfrei https://doaj.org/toc/1475-6374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 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_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 34 2019 1 1018-1029
allfieldsGer	10.1080/14756366.2019.1609953 doi (DE-627)DOAJ077852656 (DE-599)DOAJ488a172c13024fb4a68ec3b087195a07 DE-627 ger DE-627 rakwb eng RM1-950 Jorge Alberto Valle da Silva verfasserin aut Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction. acetylcholinesterase vx molecular modeling nac 7-meota-4-pa Therapeutics. Pharmacology Eugenie Nepovimova verfasserin aut Teodorico Castro Ramalho verfasserin aut Kamil Kuca verfasserin aut Tanos Celmar Costa França verfasserin aut In Journal of Enzyme Inhibition and Medicinal Chemistry Taylor & Francis Group, 2017 34(2019), 1, Seite 1018-1029 (DE-627)330383906 (DE-600)2049579-1 14756374 nnns volume:34 year:2019 number:1 pages:1018-1029 https://doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/article/488a172c13024fb4a68ec3b087195a07 kostenfrei http://dx.doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/toc/1475-6366 Journal toc kostenfrei https://doaj.org/toc/1475-6374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 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_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 34 2019 1 1018-1029
allfieldsSound	10.1080/14756366.2019.1609953 doi (DE-627)DOAJ077852656 (DE-599)DOAJ488a172c13024fb4a68ec3b087195a07 DE-627 ger DE-627 rakwb eng RM1-950 Jorge Alberto Valle da Silva verfasserin aut Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction. acetylcholinesterase vx molecular modeling nac 7-meota-4-pa Therapeutics. Pharmacology Eugenie Nepovimova verfasserin aut Teodorico Castro Ramalho verfasserin aut Kamil Kuca verfasserin aut Tanos Celmar Costa França verfasserin aut In Journal of Enzyme Inhibition and Medicinal Chemistry Taylor & Francis Group, 2017 34(2019), 1, Seite 1018-1029 (DE-627)330383906 (DE-600)2049579-1 14756374 nnns volume:34 year:2019 number:1 pages:1018-1029 https://doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/article/488a172c13024fb4a68ec3b087195a07 kostenfrei http://dx.doi.org/10.1080/14756366.2019.1609953 kostenfrei https://doaj.org/toc/1475-6366 Journal toc kostenfrei https://doaj.org/toc/1475-6374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 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_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 34 2019 1 1018-1029
language	English
source	In Journal of Enzyme Inhibition and Medicinal Chemistry 34(2019), 1, Seite 1018-1029 volume:34 year:2019 number:1 pages:1018-1029
sourceStr	In Journal of Enzyme Inhibition and Medicinal Chemistry 34(2019), 1, Seite 1018-1029 volume:34 year:2019 number:1 pages:1018-1029
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	acetylcholinesterase vx molecular modeling nac 7-meota-4-pa Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Journal of Enzyme Inhibition and Medicinal Chemistry
authorswithroles_txt_mv	Jorge Alberto Valle da Silva @@aut@@ Eugenie Nepovimova @@aut@@ Teodorico Castro Ramalho @@aut@@ Kamil Kuca @@aut@@ Tanos Celmar Costa França @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	330383906
id	DOAJ077852656
language_de	englisch
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callnumber-first	R - Medicine
author	Jorge Alberto Valle da Silva
spellingShingle	Jorge Alberto Valle da Silva misc RM1-950 misc acetylcholinesterase misc vx misc molecular modeling misc nac misc 7-meota-4-pa misc Therapeutics. Pharmacology Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach
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topic_title	RM1-950 Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach acetylcholinesterase vx molecular modeling nac 7-meota-4-pa
topic	misc RM1-950 misc acetylcholinesterase misc vx misc molecular modeling misc nac misc 7-meota-4-pa misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc acetylcholinesterase misc vx misc molecular modeling misc nac misc 7-meota-4-pa misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc acetylcholinesterase misc vx misc molecular modeling misc nac misc 7-meota-4-pa misc Therapeutics. Pharmacology
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title	Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach
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title_full	Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach
author_sort	Jorge Alberto Valle da Silva
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author_browse	Jorge Alberto Valle da Silva Eugenie Nepovimova Teodorico Castro Ramalho Kamil Kuca Tanos Celmar Costa França
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class	RM1-950
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author-letter	Jorge Alberto Valle da Silva
doi_str_mv	10.1080/14756366.2019.1609953
author2-role	verfasserin
title_sort	molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-pa, 2-pam, and obidoxime with vx-inhibited human acetylcholinesterase: a near attack conformation approach
callnumber	RM1-950
title_auth	Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach
abstract	7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction.
abstractGer	7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction.
abstract_unstemmed	7-methoxytacrine-4-pyridinealdoxime (7-MEOTA-4-PA, named hybrid 5C) is a compound formerly synthesized and evaluated in vitro, together with 4-pyridine aldoxime (4-PA) and commercial reactivators of acetylcholinesterase (AChE). This compound was designed with the purpose of being a prophylactic reactivator, capable of interacting with different subdomains of the active site of AChE. To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Then, further docking studies, molecular dynamics simulations, and molecular mechanics Poisson–Boltzmann surface area calculations, were carried out to investigate reactivation performances, considering the near attack conformation (NAC) approach, prior to the nucleophilic substitution mechanism. Our results helped to elucidate the interactions of such molecules with the different subdomains of the active site of HssAChE. Additionally, NAC poses of each oxime were suggested for further theoretical studies on the reactivation reaction.
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container_issue	1
title_short	Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach
url	https://doi.org/10.1080/14756366.2019.1609953 https://doaj.org/article/488a172c13024fb4a68ec3b087195a07 http://dx.doi.org/10.1080/14756366.2019.1609953 https://doaj.org/toc/1475-6366 https://doaj.org/toc/1475-6374
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author2	Eugenie Nepovimova Teodorico Castro Ramalho Kamil Kuca Tanos Celmar Costa França
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up_date	2024-07-03T14:31:09.876Z
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Molecular modeling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime, 4-PA, 2-PAM, and obidoxime with VX-inhibited human acetylcholinesterase: a near attack conformation approach

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