In vitro, in silico biochemical evaluation of some candidate drugs as anticancer. A Facile Rout for Synthesis of novel 3-(2-aminothiazole-4-yl)-2H-chromen-2-one-based heterocycles and their relation to physical therapy | ||
| Egyptian Journal of Chemistry | ||
| Articles in Press, Accepted Manuscript, Available Online from 20 February 2025 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejchem.2025.351834.11140 | ||
| Authors | ||
| Taha Eldebss* 1; Mohamed Alboqai2; ABDEL MONEIM ELTORGOMAN3; Shaimaa Hassanan4 | ||
| 1organic chemistry department, faculty of science , cairo university | ||
| 2Irbid National University, Irbid, Jordan | ||
| 3University of , Menoufia, Egypt | ||
| 4University of Cairo ,Giza121613 Egypt | ||
| Abstract | ||
| A new series derived from 3-(2-aminothiazole-4-yl)-2H-chromen-2-one was synthesized, characterized and its pharmacological activity toward epidermal growth factor receptor (EGFR) inhibition was screened as a part of our ongoing search for new bioactive molecules. The newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13 C- NMR and mass spectral data. A total 5 new synthesized compounds were evaluated for their in-vitro anticancer activities and their potential tumor cell growth inhibitory activity against human liver cancer cell line (HEPG-2) and human breast cancer cell line (MCF-7) and human colon cancer cell line (HCT-116). The results obtained indicated that some of such compounds showed promising anticancer activities.The most active compound of the series was 9, showing IC50 value of 4.1 μg compared to doxorubcin with IC50 of 2.1 μg and vinblatine with IC50 of 4.6 μg. Also the best computational method with exchange–correlation energy functional DFT/B3LYP/6-311++G (d,p) level of theory decided to compute molecular properties of the hybrid Coumarin derivatives (2,3-4a,4b,8 and 9). We determined the molecular electrostatic surface potential (MESP) to determine the most active site in these derivatives series with high quality informative and visualization. We have applied structure activity/property relationship for all proposed derivatives indicate that the proposed compounds exhibit good oral bioavailability and also Coumarin derivative (9) have a good biological activity which needs a drug delivery carrier to deposit on the surface of suitable nanomaterial with specific properties to enhance oral bioavailability which is very near to optimal value range. molecular docking and molecular dynamics simulation (MDS) techniques runs for 100 ns for the best docked complexes (1M17-4b and 1M17-9). Free binding energies technique MM/GBSA and PBSA are performed using snapshots taken from the systems trajectories 100 ns. These results revealed that the 1M17-9complex system acquired a relatively more stable conformation and even better descriptors than the other 1M17-4bcomplex studied systems, which indicates that it is highly amenable to inhibition Epidermal Growth Factor Receptor tyrosine kinase domain (TKD) which is excellent correlation with experimentally biological effectiveness of the designed drug construct. | ||
| Keywords | ||
| EGFR inhibitors; IC50; erltornib; molecular docking studies; coumarin | ||
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