TY  - JOUR
T1  - Molecular docking, ADMET, synthesis and anti-proliferative of novel derivatives of benzothiazine against lung cancer cell line ‎
A1  - Haider Jabbar Al-Karagully
A1  - Mohammed Kamil Hadi
JF  - Journal of Advanced Pharmacy Education and Research
JO  - J Adv Pharm Educ Res
SN  - 2249-3379
Y1  - 2025
VL  - 15
IS  - 1
DO  - 10.51847/zs9rTyYiaS
SP  - 60
EP  - 68
N2  - One of the most intriguing epigenetic targets for medication therapy is epidermal growth factor receptor tyrosine kinase (EGFR-TK). Overexpression of EGFR-TK is seen in many illnesses, including cancers. In the cnew EGFR-TK inhibitors were designed with the same consisting of erlotinib (approved anticancer drug) with longer linker and substituted hydrophobic moiety using Ligand Designer from Glide (Schrodinger LLC). By experimenting with different amide and Schiff base residues, the linker was optimized. Using licensed Schrodinger modeling software, the probable inhibition over EGFR-TK for the best-designed items was virtually assessed. The findings demonstrated that there is a possibility of an acceptable level of fitness interaction between the hydroxylated substitution hydrophobic moiety and the EGFR-TK active site. To forecast the final drugs' pharmacokinetic characteristics, an ADMET analysis was conducted. Good predicted drug-like characteristics were displayed by the final compounds. Recrystallization was used to successfully manufacture and purify the intermediates and final chemicals. FTIR, 1HNMR, and 13CNMR spectroscopy were used to characterize the chemical structure of the intermediates and final products. Using the MTT technique; all synthesized compounds (CN1-CN3) showed a reassuring antitumor performance in A504 lung cancer cells lines with IC50 of 7.58 μM, 10.08 μM, and 18.01 μM respectively, and inhibition percentages of 82.3%, 70.5%, and 65.2% respectively, which is comparable to erlotinib IC50 of 3.86 μM and inhibition percentage of 94.7%. The compound CN1 was the most promising one (IC50 = 7.58 µM and a percentage of inhibition=82.3%), compared with erlotinib, a reference authorized anticancer drug‎.
UR  - https://japer.in/article/molecular-docking-admet-synthesis-and-anti-proliferative-of-novel-derivatives-of-benzothiazine-aga-xjara3kpiyowq4d
ER  -