Prikaz osnovnih podataka o dokumentu
3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity
dc.creator | Oluić, Jelena | |
dc.creator | Nikolić, Katarina | |
dc.creator | Vučićević, Jelica | |
dc.creator | Gagić, Žarko | |
dc.creator | Filipić, Slavica | |
dc.creator | Agbaba, Danica | |
dc.date.accessioned | 2019-09-02T11:57:57Z | |
dc.date.available | 2019-09-02T11:57:57Z | |
dc.date.issued | 2017 | |
dc.identifier.issn | 1386-2073 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/2818 | |
dc.description.abstract | Aim and Objective: Altered activity of PI3K/mTOR signaling pathway is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably attractive concept in potential cancer treatment. The main aim of this work was to design novel PI3K/mTOR inhibitors with enhanced antiproliferative activity. Materials and Methods: 3D-QSAR pharmacophore modeling studies were performed on two groups comprised of 37 and 48 dual PI3K/mTOR inhibitors. Obtained 3D-pharmacophores were used in design of new dual PI3K/mTOR inhibitors. Based on the in silico ADMET data, structure-based virtual screening and docking studies, the most promising novel candidates were selected. Results: Four reliable PLS models with good statistical parameters (q(2) (=) 0.72, r(pred)(2) = 0.93; q(2) = 0.81, r(pred)(2) = 0.88 for 3D-QSAR (mTOR) models and q(2) = 0.79, r(pred)(2) = 0.93; q(2) = 0.79, r(pred)(2) = 0.94 for 3D-QSAR (PI3K) models) were obtained and new highly selective and potent dual PI3K/mTOR inhibitors were designed. Further in silico ADMET profiling of the designed compounds selected the most promising novel PI3K/mTOR inhibitors as drug candidates. Results of the 3D-QSAR studies were confirmed by structure-based virtual screening protocol that identified selected designed compounds as a best fit for PI3K and mTOR receptors. Molecular docking studies on PI3K and mTOR crystal structures revealed the key active site residues involved in binding of PI3K/mTOR ligands. Conclusion: After combining the results of 3D-QSAR, ADMET profiling, virtual screening and docking, compounds 56-57 and 56-62 were chosen as the most promising new dual PI3K/mTOR inhibitors. | 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.title | 3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Aгбаба, Даница; Филипић, Славица; Николић, Катарина; Олуић, Јелена; Вучићевић, Јелица; Гагић, Жарко; | |
dc.citation.volume | 20 | |
dc.citation.issue | 4 | |
dc.citation.spage | 292 | |
dc.citation.epage | 303 | |
dc.citation.other | 20(4): 292-303 | |
dc.citation.rank | M23 | |
dc.identifier.wos | 000408462300003 | |
dc.identifier.doi | 10.2174/1386207320666170427143858 | |
dc.identifier.pmid | 28460621 | |
dc.identifier.scopus | 2-s2.0-85028947772 | |
dc.type.version | publishedVersion |
Dokumenti
Datoteke | Veličina | Format | Pregled |
---|---|---|---|
Uz ovaj zapis nema datoteka. |