A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety
Abstract The present study involves synthesis a new series of α-aminophosphonates 2a-f and 4a-d derivatives in good yield with a simple workup via Kabachnik-Fields reaction in the presence of lithium perchlorate as Lewis acid catalyst. All the newly synthesized compounds were confirmed using various...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40265-8 |
| _version_ | 1797576726611492864 |
|---|---|
| author | Mohamed H. Baren Seham A. Ibrahim Munirah M. Al-Rooqi Saleh A. Ahmed Mohammed M. El-Gamil Hend A. Hekal |
| author_facet | Mohamed H. Baren Seham A. Ibrahim Munirah M. Al-Rooqi Saleh A. Ahmed Mohammed M. El-Gamil Hend A. Hekal |
| author_sort | Mohamed H. Baren |
| collection | DOAJ |
| description | Abstract The present study involves synthesis a new series of α-aminophosphonates 2a-f and 4a-d derivatives in good yield with a simple workup via Kabachnik-Fields reaction in the presence of lithium perchlorate as Lewis acid catalyst. All the newly synthesized compounds were confirmed using various physical, spectroscopic, and analytical data. The in vitro anticancer activities of each compound were evaluated against colorectal carcinoma Colon cancer (HCT-116) and Epdermoid carcinoma (HEP2) and also Human lung fibroblast normal cell line (WI38) compared with Doxorubicin. The results showed that Compounds 2a, 4b and 4d exhibited more potent inhibitory activity for Epdermoid Carcinoma (HEP2) compared with doxorubicin. For colon carcinoma cells (HCT-116) Compounds 2a, 2d and 4b gave the strongest activity among all compounds compared with doxorubicin. Moreover, all designed structures were docked into the active site of VEGFR2 and FGFR1 proteins. The result reveals that compound 2b and have the strongest inhibitory activity of the VEGFR2 and FGFR1 proteins indicating that these substances might conceivably operate as VEGFR2 and FGFR1 inhibitors and hence might take role in anticancer activities with various binding interactions. The 3D-QSAR models produced strong statistical results since they were defined by PLS factors 4 and confirmed by parameters as R2, R2 CV, Stability, F-value, P-value, RMSE, Q2, and Pearson-r. |
| first_indexed | 2024-03-10T21:57:49Z |
| format | Article |
| id | doaj.art-d09950ff858048d2a5ccf34b1d45d1b4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T21:57:49Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d09950ff858048d2a5ccf34b1d45d1b42023-11-19T13:04:29ZengNature PortfolioScientific Reports2045-23222023-09-0113112010.1038/s41598-023-40265-8A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moietyMohamed H. Baren0Seham A. Ibrahim1Munirah M. Al-Rooqi2Saleh A. Ahmed3Mohammed M. El-Gamil4Hend A. Hekal5Chemistry Department, Faculty of Science, Tanta UniversityChemistry Department, Faculty of Science, Tanta UniversityDepartment of Chemistry, Faculty of Applied Sciences, Umm Al-Qura UniversityDepartment of Chemistry, Faculty of Applied Sciences, Umm Al-Qura UniversityDepartment of Toxic and Narcotic Drug, Forensic Medicine, Mansoura Laboratory, Medico legal Organization, Ministry of JusticeChemistry Department, Faculty of Science, Tanta UniversityAbstract The present study involves synthesis a new series of α-aminophosphonates 2a-f and 4a-d derivatives in good yield with a simple workup via Kabachnik-Fields reaction in the presence of lithium perchlorate as Lewis acid catalyst. All the newly synthesized compounds were confirmed using various physical, spectroscopic, and analytical data. The in vitro anticancer activities of each compound were evaluated against colorectal carcinoma Colon cancer (HCT-116) and Epdermoid carcinoma (HEP2) and also Human lung fibroblast normal cell line (WI38) compared with Doxorubicin. The results showed that Compounds 2a, 4b and 4d exhibited more potent inhibitory activity for Epdermoid Carcinoma (HEP2) compared with doxorubicin. For colon carcinoma cells (HCT-116) Compounds 2a, 2d and 4b gave the strongest activity among all compounds compared with doxorubicin. Moreover, all designed structures were docked into the active site of VEGFR2 and FGFR1 proteins. The result reveals that compound 2b and have the strongest inhibitory activity of the VEGFR2 and FGFR1 proteins indicating that these substances might conceivably operate as VEGFR2 and FGFR1 inhibitors and hence might take role in anticancer activities with various binding interactions. The 3D-QSAR models produced strong statistical results since they were defined by PLS factors 4 and confirmed by parameters as R2, R2 CV, Stability, F-value, P-value, RMSE, Q2, and Pearson-r.https://doi.org/10.1038/s41598-023-40265-8 |
| spellingShingle | Mohamed H. Baren Seham A. Ibrahim Munirah M. Al-Rooqi Saleh A. Ahmed Mohammed M. El-Gamil Hend A. Hekal A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety Scientific Reports |
| title | A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety |
| title_full | A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety |
| title_fullStr | A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety |
| title_full_unstemmed | A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety |
| title_short | A new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety |
| title_sort | new class of anticancer activity with computational studies for a novel bioactive aminophosphonates based on pyrazole moiety |
| url | https://doi.org/10.1038/s41598-023-40265-8 |
| work_keys_str_mv | AT mohamedhbaren anewclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT sehamaibrahim anewclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT munirahmalrooqi anewclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT salehaahmed anewclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT mohammedmelgamil anewclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT hendahekal anewclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT mohamedhbaren newclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT sehamaibrahim newclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT munirahmalrooqi newclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT salehaahmed newclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT mohammedmelgamil newclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety AT hendahekal newclassofanticanceractivitywithcomputationalstudiesforanovelbioactiveaminophosphonatesbasedonpyrazolemoiety |