Synthesis, Biological Evaluation, 2D-QSAR, and Molecular Simulation Studies of Dihydropyrimidinone Derivatives as Alkaline Phosphatase Inhibitors was written by Altaf, Reem;Nadeem, Humaira;Iqbal, Muhammad Nasir;Ilyas, Umair;Ashraf, Zaman;Imran, Muhammad;Muhammad, Syed Aun. And the article was included in ACS Omega in 2022.Category: chlorides-buliding-blocks The following contents are mentioned in the article:
The presence of alk. phosphatases has been observed in several species and has been known to play a crucial role in various biol. functions. Higher expressions of alk. phosphatase have been found in several multifactorial disorders and cancer patients, which has led it to be an interesting target for drug discovery. A strong structural similarity exists between intestinal alk. phosphatases (IAPs) and tissue-nonspecific alk. phosphatases (TNAPs), which has led to the discovery of only a few selective inhibitors. Therefore, a series of 22 derivatives of 6-(chloromethyl)-4-(4-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate and Et 6-(chloromethyl)-4-(2-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate were synthesized to evaluate the anticancer potential of these compounds against breast cancer. The compounds were characterized through spectral and elemental analyses. The inhibitory effect of dihydropyrimidinone derivatives on alk. phosphatases was evaluated using the calf alk. phosphatase assay. The antioxidant activity of these compounds was performed to study the radical scavenging effect. In silico mol. docking and mol. dynamic simulations were performed to elucidate the binding mode of active compounds Moreover, the two-dimensional qual.-structure-activity relationship (2D-QSAR) was performed to study the structural requirements for enzyme inhibition. The calf alk. phosphatase inhibitory assay revealed significant inhibition of the enzyme by compound I with IC50 1.27μM at 0.1 mM concentration as compared to standard KH2PO4 having IC50 2.80μM. Several compounds also showed very good inhibition with IC50 values of 2.502, 2.943, and 2.132μM, resp., at the same concentration The antioxidant assay revealed efficient radical scavenging activity of three compounds at 100μg/mL with IC50 values of 0.48, 0.61, and 0.75μg/mL, resp. The mol. docking and simulation studies revealed efficient binding of active compounds in the active binding site of the target enzyme. The final QSAR equation revealed good predictivity and statistical validation having R2 = 0.958 and Q2 = 0.903, resp., for the generated model. The compound I showed the highest inhibitory activity with stable binding modes acting as a future lead for identifying alk. phosphatase inhibitors. The mol. simulations suggested the stable binding of this compound, and the QSAR studies revealed the importance of autocorrelated descriptors in the inhibition of alk. phosphatase. The investigated compounds may serve as potential pharmacophores for potent and selective alk. phosphatase inhibitors. We intend to further investigate the biol. activities of these compounds as alk. phosphatase inhibitors. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Category: chlorides-buliding-blocks).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. Alkanes and aryl alkanes may be chlorinated under free radical conditions, with UV light. However, the extent of chlorination is difficult to control.Category: chlorides-buliding-blocks
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics