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dc.creatorKovaević, Strahinja
dc.creatorKaradzić-Banjac, Milica
dc.creatorPodunavac-Kuzmanović, Sanja
dc.creatorMilošević, Nataša
dc.creatorCurcić, Jelena
dc.creatorVulić, Jelena
dc.creatorSeregelj, Vanja
dc.creatorBanjac, Nebojša
dc.creatorUšćumlić, Gordana
dc.date.accessioned2020-12-17T22:54:04Z
dc.date.available2020-12-17T22:54:04Z
dc.date.issued2020
dc.identifier.issn1476-9271
dc.identifier.urihttp://aspace.agrif.bg.ac.rs/handle/123456789/5331
dc.description.abstractThe present study is focused on a series of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimide derivatives, as potential anticonvulsants. The retention behavior of eleven succinimide derivatives was determined by using reversed phase high performance liquid chromatography (RP-HPLC) and reversed phase high performance thin layer chromatography (RP-HPTLC). The estimated retention behavior was correlated with partition (logP) and distribution coefficients (logD). These high correlations pointed out that the determined retention parameters (logK(0) and R-M(0)) can be considered chromatographic (anisotropic) lipophilicity of the studied succinimide derivatives. The structural properties, which dominantly affect the chromatographic lipophilicity, were determined as well. The significant correlations between the chromatographic lipophilicity and plasma protein binding (PPB), Madin-Darby Canine Kidney (MDCK) cells permeability, volume of distribution (Vd) and absorption constant (Ka) indicate the strong influence of lipophilicity on pharmacokinetics of 1-aryl-3-ethyl-3-methylsuccinimide derivatives. These derivatives have also been tested applying Comprehensive Medicinal Chemistry (CMC) drug-like rules which confirmed their drug-like properties. Besides, their blood-brain penetration (BBB) ability has been estimated applying the set of Clark's rules and by using Pre-ADMET software. Regarding toxicity, it was predicted that only one compound from the set might have toxic effects by blocking the hERG potassium channel. The present study reveals which molecular features in the structure of novel succinimide derivatives could be crucial for their lipophilicity, and consequently for their pharmacokinetic properties. The results indicate that the newly synthesized series of succinimide derivatives should be further considered in design of novel anticonvulsants.en
dc.publisherElsevier Sci Ltd, Oxford
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172012/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172013/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172014/RS//
dc.rightsrestrictedAccess
dc.sourceComputational Biology and Chemistry
dc.subjectADMETen
dc.subjectChromatographyen
dc.subjectLipophilicityen
dc.subjectPharmacokineticsen
dc.subjectQSRRen
dc.subjectSuccinimideen
dc.titleChromatographic and computational screening of anisotropic lipophilicity and pharmacokinetics of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimidesen
dc.typearticle
dc.rights.licenseARR
dc.citation.other84: -
dc.citation.rankM22
dc.citation.volume84
dc.identifier.doi10.1016/j.compbiolchem.2019.107161
dc.identifier.scopus2-s2.0-85076526384
dc.identifier.pmid31787580
dc.identifier.wos000510947400019
dc.type.versionpublishedVersion


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