Structural studies, DFT based computational analysis and inhibitory potential of 2H-pyrido[1,2-a] pyrimidine-2,4(3H)-dione and 4-hydroxy-1,8-naphthyridin-2(1H)-one against MEK2

This paper describes the synthesis, spectroscopic characterization, in-vitro activity on A549 cell line, density functional theory, structure-activity relationship, molecular docking and ADMET evaluation of 2H-pyrido[1,2-a] pyrimidine-2,4(3H)-dione (PY) and 4-hydroxy-1,8-naphthyridin-2(1H)-one (NI). It was discovered that PY and NI showed moderate cytotoxicity against A549 cell line. Both the compounds PY and NI shows a remarkable decrease in the % cell viability of approx. 23% and 22% respectively. The ADMET analysis predicted a stronger effect for the P-glycoprotein activity. The first hyperpolarizabilities (β0) were found to be 2.21*10⁻³⁰esu (PY) and 5.79*10⁻³⁰esu (NI) respectively and compared with the standard reference urea. It was observed that the chemical reactivity of NI was better as compared to PY and ultimately it may be regarded as a good synthetic intermediate for the synthesis of a number of bioactive heterocycles like Vosaroxin, Gemifloxacin, quinazolines and many more. The two isomeric pyridine derivatives (PY and NI) were synthesized.<i>In-silico</i> studies of PY and NI include DFT, Molecular dynamics, ADMET, etc.The experimental values of PY and NI were in agreement with the theoretical results.PY and NI were investigated on the basis of ADMET and docking score and compared with Gilotrif.Compound NI was found most potent against the cancer cell line (A549). The two isomeric pyridine derivatives (PY and NI) were synthesized. <i>In-silico</i> studies of PY and NI include DFT, Molecular dynamics, ADMET, etc. The experimental values of PY and NI were in agreement with the theoretical results. PY and NI were investigated on the basis of ADMET and docking score and compared with Gilotrif. Compound NI was found most potent against the cancer cell line (A549).