| Yazarlar (4) |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
Halil Şenol
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
|
Şeyma Bulut
Türkiye |
|
Fahri Akbaş
Türkiye |
| Özet |
| In this study, we synthesized 15 novel quinazoline-morpholinobenzylideneamino hybrid compounds from methyl anthranilate and we assessed their cytotoxicity via in vitro assays against A549 and BEAS-2B cell lines. Molecular docking studies were conducted to evaluate the protein-ligand interactions and inhibition mechanisms on nine different molecular targets, while molecular dynamics (MD) simulations were carried out to assess the stability of the best docked ligand-protein complexes. Additionally, ADME prediction was carried out to determine physicochemical parameters and drug likeness. According to the cytotoxicity assays, compound 1 (IC = 2.83 μM) was found to be the most active inhibitor against A549 cells. While the selectivity index (SI) of compound 1 is 29, the SI of the reference drugs paclitaxel and sorafenib, used in this study, are 2.40 and 4.92, respectively. Among the hybrid compounds, 1 has the best docking scores against VEGFR1 (-11.744 kcal/mol), VEGFR2 (-12.407 kcal/mol) and EGFR (-10.359 kcal/mol). During MD simulations, compound 1 consistently exhibited strong hydrogen bond interactions with the active sites of VEGFR1 and 2, and these interactions were maintained for more than 90% of the simulation time. Additionally, the RMSD and RMSF values of the ligand-protein complexes exhibited high stability at their minimum levels around 1-2 Å. In conclusion, these findings suggest that compound 1 may be a potent and selective inhibitor candidate for lung cancer treatment and inhibition of VEGFR2, especially. |
| Anahtar Kelimeler |
| cytotoxicity | in silico | lung cancer | morpholinobenzylidene | quinazoline-4(3H)-one |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | Chemical Biology & Drug Design |
| Dergi ISSN | 1747-0277 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 07-2024 |
| Cilt No | 104 |
| Sayı | 1 |
| Doi Numarası | 10.1111/cbdd.14599 |
| Makale Linki | https://doi.org/10.1111/cbdd.14599 |
| Atıf Sayıları | |
| WoS | 12 |
