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Imidazoline-1 Receptor Ligands as Apoptotic Agents: Pharmacophore Modeling and Virtual Docking Study
dc.creator | Nikolić, Katarina | |
dc.creator | Veljković, Nevena | |
dc.creator | Gemović, Branislava | |
dc.creator | Srdić-Rajić, Tatjana | |
dc.creator | Agbaba, Danica | |
dc.date.accessioned | 2019-09-02T11:34:41Z | |
dc.date.available | 2019-09-02T11:34:41Z | |
dc.date.issued | 2013 | |
dc.identifier.issn | 1386-2073 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/1933 | |
dc.description.abstract | The group of imidazoline-1 receptors (I-1-IR) agonists encompasses drugs are currently used in treatment of high blood pressure and hyperglycemia. The I-1-IR protein structures have not been determined yet, but Nischarin protein that binds numerous imidazoline ligands inducing initiation of various cell-signaling cascades, including apoptosis, is identified as strong I-1-IR candidate. In this study we examined apoptotic activity of rilmenidine (potent I-1-IR agonist), moxonidine (moderate I-1-IR agonist), and efaroxan (I-1-IR partial agonist) on cancer cell line (K562) expressing Nischarin. The Nischarine domains mapping was performed by use of the Informational Spectrum Method (ISM). The 3D-Quantitative Structure-Activity Relationship (3D-QSAR) and virtual docking studies of 29 I-1-IR ligands (agonists, partial agonists, and antagonists) were carried out on I-1-IR receptors binding affinities. The 3D-QSAR study defined 3D-pharmacophore models for I-1-IR agonistic and I-1-IR antagonistic activity and created regression model for prediction of I-1-IR activity of novel compounds. The 3D-QSAR models were applied for design and evaluation of novel I-1-IR agonists and I-1-IR antagonists. The most promising I-1-IR ligands with enhanced activities than parent compounds were proposed for synthesis. The results of 3D-QSAR, ISM, and virtual docking studies were in perfect agreement and allowed precise definition of binding mode of I-1-IR agonists (Arg 758, Arg 866, Val 981, and Glu 1057) and significantly different binding modes of I-1-IR antagonists or partial I-1-IR agonists. The performed theoretical study provides reliable system for evaluation of I-1-IR agonistic and I-1-IR antagonistic activity of novel I-1-IR ligands, as drug candidates with anticancer activities. | en |
dc.publisher | Bentham Science Publ Ltd, Sharjah | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172033/RS// | |
dc.rights | restrictedAccess | |
dc.source | Combinatorial Chemistry & High Throughput Screening | |
dc.subject | Apoptotic activity | en |
dc.subject | I-1-imidazoline receptor | en |
dc.subject | I-1-IR agonist | en |
dc.subject | I-1-IR antagonist | en |
dc.subject | pharmacophore modeling | en |
dc.subject | structure activity relationship | en |
dc.subject | virtual docking | en |
dc.title | Imidazoline-1 Receptor Ligands as Apoptotic Agents: Pharmacophore Modeling and Virtual Docking Study | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Срдић-Рајић, Татјана; Николић, Катарина; Aгбаба, Даница; Гемовић, Бранислава; Вељковић, Невена; | |
dc.citation.volume | 16 | |
dc.citation.issue | 4 | |
dc.citation.spage | 298 | |
dc.citation.epage | 319 | |
dc.citation.other | 16(4): 298-319 | |
dc.citation.rank | M22 | |
dc.identifier.wos | 000317058100004 | |
dc.identifier.doi | 10.2174/1386207311316040004 | |
dc.identifier.pmid | 23360165 | |
dc.identifier.scopus | 2-s2.0-84877962730 | |
dc.type.version | publishedVersion |