Synthesis, molecular modeling, DFT studies, and EPR analysis of 1,4-dihydropyridines as potential calcium channel blockers

Basit Öğe Kaydı
dc.contributor.authorAslan, Ebru Koçak
dc.contributor.authorLam, Kevin
dc.contributor.authorDengiz, Çağatay
dc.contributor.authorDenzinger K.
dc.contributor.authorErdamar, Işık Yeşim Dicle
dc.contributor.authorHuang, Sun
dc.contributor.authorWolber, Gerhard
dc.date.accessioned2024-04-24T17:56:09Z
dc.date.available2024-04-24T17:56:09Z
dc.date.issued2024
dc.departmentDicle Üniversitesi, Ziya Gökalp Eğitim Fakültesi, Matematik ve Fen Bilimleri Eğitimi Bölümüen_US
dc.description.abstract1,4-Dihydropyridines (DHPs) are widely recognized as a highly effective class of L-type calcium channel blockers that offer significant therapeutic potential in managing cardiovascular conditions. Furthermore, their ability to target other types of calcium channels makes DHPs attractive candidates for therapeutic applications in neurological and psychiatric disorders. Close examination of the chemical structures of approved DHP-based antihypertensive drugs with a history of over forty years in the market reveals that the C-4 position is the least altered part of this privileged ring system. In the present study, we focused on this position and synthesized two novel compounds (DB1 and DB2) by carrying out chemical modifications on suitable positions of the main scaffold of DA1 (isobutyl 4-(benzo[d][1,3]dioxol-5-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) that was previously identified as a DHP-based effective and selective inhibitor of T-type (Cav3.2) over L-type (Cav1.2) calcium channel. Based on whole-cell patch-clamp analysis on Cav1.2 and Cav3.2, DB1 with bromine group on the benzodioxole ring appeared to be a more effective and selective inhibitor of Cav3.2 compared to DB2 with nitro at the same locus. Molecular docking and molecular dynamics (MD) simulations were performed to investigate the binding mode of both DB1 isomers to Cav3.2. Furthermore, density functional theory (DFT) methods were employed to obtain information regarding the stability of the molecules by computing various parameters, such as electric dipole moment, band gap, electronegativity, and global chemical hardness-softness, related to their charge-transfer characteristics. According to DFT studies, DB1 also appeared to be chemically more stable than DB2. Finally, ionizing radiation-induced free radicals of gamma-irradiated DB1 and DB2 in powder form were examined utilizing the electron paramagnetic resonance (EPR) technique and the obtained data demonstrated that radiation sterilization is suitable for the dosage forms including DB1 and DB2. © 2024 Elsevier B.V.en_US
dc.identifier.citationAslan, E. K., Lam, K., Dengiz, Ç., Denzinger, K., Erdamar, I. Y. D., Huang, S. ve diğerleri. (2024). Synthesis, molecular modeling, DFT studies, and EPR analysis of 1,4-dihydropyridines as potential calcium channel blockers. Journal of Molecular Structure, 1307, 1-13.
dc.identifier.doi10.1016/j.molstruc.2024.137983
dc.identifier.issn0022-2860
dc.identifier.scopus2-s2.0-85188795259
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2024.137983
dc.identifier.urihttps://hdl.handle.net/11468/23334
dc.identifier.volume1307en_US
dc.indekslendigikaynakScopus
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofJournal of Molecular Structure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subject3d Pharmacophoreen_US
dc.subjectBenzodioxoleen_US
dc.subjectChemical stabilityen_US
dc.subjectDihydropyridineen_US
dc.subjectHexahydroquinolineen_US
dc.subjectMolecular dynamicsen_US
dc.titleSynthesis, molecular modeling, DFT studies, and EPR analysis of 1,4-dihydropyridines as potential calcium channel blockersen_US
dc.titleSynthesis, molecular modeling, DFT studies, and EPR analysis of 1,4-dihydropyridines as potential calcium channel blockers
dc.typeArticleen_US

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
[ X ]
İsim:
Synthesis, molecular modeling, DFT studies, and EPR analysis of 1,4-dihydropyridines as potential calcium channel blockers.pdf
Boyut:
11.13 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Makale Dosyası
İndir

Koleksiyon

Scopus İndeksli Yayınlar Koleksiyonu
Matematik ve Fen Bilimleri Eğitimi Bölümü Koleksiyonu