The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study
Само за регистроване кориснике
2022
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Adrenergic receptors are among the most studied G protein-coupled receptors. Activation or blockade of these receptors is a major therapeutic approach for the treatment of numerous disorders such as cardiac hypertrophy, congestive heart failure, hypertension, angina pectoris, cardiac arrhythmias, depression, benign prostate hyperplasia, anaphylaxis, asthma, and hyperthyroidism. Among all nine cloned adrenoceptor subtypes and the subsequent development of animal models, a significant target for various neurological conditions treatment is alpha1-adrenergic receptors. 2-{[4-(2-Methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles, their 5 substituted derivatives, and structurally similar, arylpiperazine based alpha1-adrenergic receptors antagonists (trazodone, naftopidil, and urapidil) have been subjects of comparative analysis. Most of the novel compounds showed alpha1-adrenergic affinity in the range from 22 nM to 250 nM. The in silico docking and molecular dynamics simulations, bi...nding data together with absorption, distribution, metabolism, and excretion (ADME) calculations identified the promising lead compounds. The results brought out the conclusions which allowed us to propose a rationale for the activity of these molecules and to highlight six compounds (2-5, 8, and 12) that exhibited an acceptable pharmacokinetic profile to the advanced investigation as the potential alpha1-adrenergic receptor antagonists.
Кључне речи:
Alpha1-adrenergic receptors / Arylpiperazines / Binding assay / Docking analyses / Molecular dynamics simulations / PharmacokineticsИзвор:
Applied Biochemistry and Biotechnology, 2022, 194, 3749-3764Издавач:
- Springer
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200026 (Универзитет у Београду, Институт за хемију, технологију и металургију - ИХТМ) (RS-MESTD-inst-2020-200026)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200168 (Универзитет у Београду, Хемијски факултет) (RS-MESTD-inst-2020-200168)
DOI: 10.1007/s12010-022-03922-8
ISSN: 1559-0291; 0273-2289
PubMed: 35507251
WoS: 00079063420000
Scopus: 2-s2.0-85129642501
Институција/група
IHTMTY - JOUR AU - Penjišević, Jelena AU - Šukalović, Vladimir AU - Andrić, Deana AU - Suručić, Relja AU - Kostić Rajačić, Slađana PY - 2022 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/5229 AB - Adrenergic receptors are among the most studied G protein-coupled receptors. Activation or blockade of these receptors is a major therapeutic approach for the treatment of numerous disorders such as cardiac hypertrophy, congestive heart failure, hypertension, angina pectoris, cardiac arrhythmias, depression, benign prostate hyperplasia, anaphylaxis, asthma, and hyperthyroidism. Among all nine cloned adrenoceptor subtypes and the subsequent development of animal models, a significant target for various neurological conditions treatment is alpha1-adrenergic receptors. 2-{[4-(2-Methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles, their 5 substituted derivatives, and structurally similar, arylpiperazine based alpha1-adrenergic receptors antagonists (trazodone, naftopidil, and urapidil) have been subjects of comparative analysis. Most of the novel compounds showed alpha1-adrenergic affinity in the range from 22 nM to 250 nM. The in silico docking and molecular dynamics simulations, binding data together with absorption, distribution, metabolism, and excretion (ADME) calculations identified the promising lead compounds. The results brought out the conclusions which allowed us to propose a rationale for the activity of these molecules and to highlight six compounds (2-5, 8, and 12) that exhibited an acceptable pharmacokinetic profile to the advanced investigation as the potential alpha1-adrenergic receptor antagonists. PB - Springer T2 - Applied Biochemistry and Biotechnology T1 - The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study VL - 194 SP - 3749 EP - 3764 DO - 10.1007/s12010-022-03922-8 ER -
@article{ author = "Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Suručić, Relja and Kostić Rajačić, Slađana", year = "2022", abstract = "Adrenergic receptors are among the most studied G protein-coupled receptors. Activation or blockade of these receptors is a major therapeutic approach for the treatment of numerous disorders such as cardiac hypertrophy, congestive heart failure, hypertension, angina pectoris, cardiac arrhythmias, depression, benign prostate hyperplasia, anaphylaxis, asthma, and hyperthyroidism. Among all nine cloned adrenoceptor subtypes and the subsequent development of animal models, a significant target for various neurological conditions treatment is alpha1-adrenergic receptors. 2-{[4-(2-Methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles, their 5 substituted derivatives, and structurally similar, arylpiperazine based alpha1-adrenergic receptors antagonists (trazodone, naftopidil, and urapidil) have been subjects of comparative analysis. Most of the novel compounds showed alpha1-adrenergic affinity in the range from 22 nM to 250 nM. The in silico docking and molecular dynamics simulations, binding data together with absorption, distribution, metabolism, and excretion (ADME) calculations identified the promising lead compounds. The results brought out the conclusions which allowed us to propose a rationale for the activity of these molecules and to highlight six compounds (2-5, 8, and 12) that exhibited an acceptable pharmacokinetic profile to the advanced investigation as the potential alpha1-adrenergic receptor antagonists.", publisher = "Springer", journal = "Applied Biochemistry and Biotechnology", title = "The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study", volume = "194", pages = "3749-3764", doi = "10.1007/s12010-022-03922-8" }
Penjišević, J., Šukalović, V., Andrić, D., Suručić, R.,& Kostić Rajačić, S.. (2022). The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study. in Applied Biochemistry and Biotechnology Springer., 194, 3749-3764. https://doi.org/10.1007/s12010-022-03922-8
Penjišević J, Šukalović V, Andrić D, Suručić R, Kostić Rajačić S. The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study. in Applied Biochemistry and Biotechnology. 2022;194:3749-3764. doi:10.1007/s12010-022-03922-8 .
Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Suručić, Relja, Kostić Rajačić, Slađana, "The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study" in Applied Biochemistry and Biotechnology, 194 (2022):3749-3764, https://doi.org/10.1007/s12010-022-03922-8 . .