Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative Activity
A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF<sup>V600E</sup>. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds <b...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/16/11/1522 |
| _version_ | 1827639050034479104 |
|---|---|
| author | Lamya H. Al-Wahaibi Mohamed Hisham Hesham A. Abou-Zied Heba A. Hassan Bahaa G. M. Youssif Stefan Bräse Alaa M. Hayallah Mohamed Abdel-Aziz |
| author_facet | Lamya H. Al-Wahaibi Mohamed Hisham Hesham A. Abou-Zied Heba A. Hassan Bahaa G. M. Youssif Stefan Bräse Alaa M. Hayallah Mohamed Abdel-Aziz |
| author_sort | Lamya H. Al-Wahaibi |
| collection | DOAJ |
| description | A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF<sup>V600E</sup>. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds <b>8</b>, <b>9</b>, <b>18</b>, and <b>19</b> inhibited cell proliferation significantly in the four cancer cells, with GI<sub>50</sub> values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI<sub>50</sub> = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAF<sup>V600E</sup>. Molecular docking investigations provided confirmation that compounds <b>18</b> and <b>19</b> possess the capability to inhibit EGFR and BRAF<sup>V600E</sup>. Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects. |
| first_indexed | 2024-03-09T16:32:15Z |
| format | Article |
| id | doaj.art-58fc1dca95434f25acd7ae4f3ad765aa |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:15Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-58fc1dca95434f25acd7ae4f3ad765aa2023-11-24T15:00:02ZengMDPI AGPharmaceuticals1424-82472023-10-011611152210.3390/ph16111522Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative ActivityLamya H. Al-Wahaibi0Mohamed Hisham1Hesham A. Abou-Zied2Heba A. Hassan3Bahaa G. M. Youssif4Stefan Bräse5Alaa M. Hayallah6Mohamed Abdel-Aziz7Department of Chemistry, College of Sciences, Princess Nourah Bint Abdulrahman University, Riyadh 11564, Saudi ArabiaPharmaceutical Chemistry Department, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia City 61111, EgyptPharmaceutical Chemistry Department, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia City 61111, EgyptMedicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, EgyptPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptInstitute of Biological and Chemical Systems, IBCS-FMS, Karlsruhe Institute of Technology, 76131 Karlsruhe, GermanyPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptMedicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, EgyptA novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF<sup>V600E</sup>. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds <b>8</b>, <b>9</b>, <b>18</b>, and <b>19</b> inhibited cell proliferation significantly in the four cancer cells, with GI<sub>50</sub> values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI<sub>50</sub> = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAF<sup>V600E</sup>. Molecular docking investigations provided confirmation that compounds <b>18</b> and <b>19</b> possess the capability to inhibit EGFR and BRAF<sup>V600E</sup>. Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.https://www.mdpi.com/1424-8247/16/11/1522quinazolin-4-one3-cyanopyridin-2-oneEGFRBRAF<sup>V600E</sup>anti-cancerdocking |
| spellingShingle | Lamya H. Al-Wahaibi Mohamed Hisham Hesham A. Abou-Zied Heba A. Hassan Bahaa G. M. Youssif Stefan Bräse Alaa M. Hayallah Mohamed Abdel-Aziz Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative Activity Pharmaceuticals quinazolin-4-one 3-cyanopyridin-2-one EGFR BRAF<sup>V600E</sup> anti-cancer docking |
| title | Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative Activity |
| title_full | Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative Activity |
| title_fullStr | Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative Activity |
| title_full_unstemmed | Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative Activity |
| title_short | Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF<sup>V600E</sup>: Design, Synthesis, and Antiproliferative Activity |
| title_sort | quinazolin 4 one 3 cyanopyridin 2 one hybrids as dual inhibitors of egfr and braf sup v600e sup design synthesis and antiproliferative activity |
| topic | quinazolin-4-one 3-cyanopyridin-2-one EGFR BRAF<sup>V600E</sup> anti-cancer docking |
| url | https://www.mdpi.com/1424-8247/16/11/1522 |
| work_keys_str_mv | AT lamyahalwahaibi quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity AT mohamedhisham quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity AT heshamaabouzied quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity AT hebaahassan quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity AT bahaagmyoussif quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity AT stefanbrase quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity AT alaamhayallah quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity AT mohamedabdelaziz quinazolin4one3cyanopyridin2onehybridsasdualinhibitorsofegfrandbrafsupv600esupdesignsynthesisandantiproliferativeactivity |