3D molecular pharmacophore determination of PI3K-α kinase inhibitors
Apstrakt
PI3K-α, as an enzyme with increased activity in many types of cancer,
represents important target for research of new cytostatic agents. 3D-QSAR
study was applied on 92 PI3K-α inhibitors in order to determine molecular
pharmacophore structure. Obtained validation parameters (R2=0.84; Q2=0.67,
R2
pred=0.681) indicate on reliability and good predictive potential of the 3DQSAR
model. Pharmacophore analysis showed that following structural
characteristic have the greatest impact on activity of PI3K-α inhibitors:
presence of hydrogen bond donor and hydrogen bond acceptor at a distance
of 18-18.4Å or 12-12.4Å, presence of hydrophobic domain and hydrogen
bond donor at a distance of 15.2-15.6Å, presence of steric hot spot and
hydrogen bond donor at a distance of 1.6-2Å and presence of hydrogen bond
acceptor and steric hot spot at a distance of 14.4-14.8Å. These findings
provide guidelines for future design of new PI3K-α inhibitors with enhanced
activity.
Izvor:
Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, 2018, I, 97-100Izdavač:
- Society of Physical Chemists of Serbia
Finansiranje / projekti:
- Sinteza, kvantitativni odnos između strukture i dejstva, fizičko-hemijska karakterizacija i analiza farmakološki aktivnih supstanci (RS-MESTD-Basic Research (BR or ON)-172033)
Napomena:
- 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 24–28, 2018, Belgrade
Institucija/grupa
PharmacyTY - CONF AU - Gagić, Žarko AU - Jovanović, Milan AU - Agbaba, Danica AU - Nikolić, Katarina PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4851 AB - PI3K-α, as an enzyme with increased activity in many types of cancer, represents important target for research of new cytostatic agents. 3D-QSAR study was applied on 92 PI3K-α inhibitors in order to determine molecular pharmacophore structure. Obtained validation parameters (R2=0.84; Q2=0.67, R2 pred=0.681) indicate on reliability and good predictive potential of the 3DQSAR model. Pharmacophore analysis showed that following structural characteristic have the greatest impact on activity of PI3K-α inhibitors: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12-12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, presence of steric hot spot and hydrogen bond donor at a distance of 1.6-2Å and presence of hydrogen bond acceptor and steric hot spot at a distance of 14.4-14.8Å. These findings provide guidelines for future design of new PI3K-α inhibitors with enhanced activity. PB - Society of Physical Chemists of Serbia C3 - Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry T1 - 3D molecular pharmacophore determination of PI3K-α kinase inhibitors VL - I SP - 97 EP - 100 UR - https://hdl.handle.net/21.15107/rcub_farfar_4851 ER -
@conference{ author = "Gagić, Žarko and Jovanović, Milan and Agbaba, Danica and Nikolić, Katarina", year = "2018", abstract = "PI3K-α, as an enzyme with increased activity in many types of cancer, represents important target for research of new cytostatic agents. 3D-QSAR study was applied on 92 PI3K-α inhibitors in order to determine molecular pharmacophore structure. Obtained validation parameters (R2=0.84; Q2=0.67, R2 pred=0.681) indicate on reliability and good predictive potential of the 3DQSAR model. Pharmacophore analysis showed that following structural characteristic have the greatest impact on activity of PI3K-α inhibitors: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12-12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, presence of steric hot spot and hydrogen bond donor at a distance of 1.6-2Å and presence of hydrogen bond acceptor and steric hot spot at a distance of 14.4-14.8Å. These findings provide guidelines for future design of new PI3K-α inhibitors with enhanced activity.", publisher = "Society of Physical Chemists of Serbia", journal = "Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry", title = "3D molecular pharmacophore determination of PI3K-α kinase inhibitors", volume = "I", pages = "97-100", url = "https://hdl.handle.net/21.15107/rcub_farfar_4851" }
Gagić, Ž., Jovanović, M., Agbaba, D.,& Nikolić, K.. (2018). 3D molecular pharmacophore determination of PI3K-α kinase inhibitors. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry Society of Physical Chemists of Serbia., I, 97-100. https://hdl.handle.net/21.15107/rcub_farfar_4851
Gagić Ž, Jovanović M, Agbaba D, Nikolić K. 3D molecular pharmacophore determination of PI3K-α kinase inhibitors. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry. 2018;I:97-100. https://hdl.handle.net/21.15107/rcub_farfar_4851 .
Gagić, Žarko, Jovanović, Milan, Agbaba, Danica, Nikolić, Katarina, "3D molecular pharmacophore determination of PI3K-α kinase inhibitors" in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, I (2018):97-100, https://hdl.handle.net/21.15107/rcub_farfar_4851 .