25063-55-2Relevant academic research and scientific papers
Facile one-pot synthesis, butyrylcholinesterase and α-glucosidase inhibitory activities, structure–activity relationship, molecular docking and DNA–drug binding analysis of Meldrum’s acid derivatives
Mehfooz, Haroon,Saeed, Aamer,Faisal, Muhammad,Larik, Fayaz Ali,Muqadar, Urooj,Khatoon, Saira,Channar, Pervaiz Ali,Ismail, Hammad,Bilquees, Salma,Rashid, Sajid,Shafique, Shagufta,Mirza, Bushra,Dilshad, Erum,Ahmad, Fawad
, p. 2437 - 2456 (2020)
Meldrum’s acid derivatives were facile synthesized by one-pot condensation process and characterized by NMR (1H, 13C, DEPT-90 and DEPT-135) and EI-MS. The synthesized compounds were screened for their potential to inhibit butyrylcholinesterase (BChE) and α-glucosidase enzymes. Interestingly, the derivative 3a showed potent α-glucosidase inhibitory activity, with the IC50 value equal to 2.1?mg/mL as compared to standard acarbose (IC50 = 4.7?mg/mL), whereas, in terms of BChE inhibitory activity investigation, the derivatives 3a and 3c showed novel results, with the IC50 values equal to 1.2 and 2.9?mg/mL, respectively, as compared to standard galantamine hydrobromide (IC50 = 4.7?mg/mL), making derivative 3a a dual inhibitor of both enzymes. Further, structure–activity relationship, comparative molecular docking analysis and the DNA–drug binding interaction were studied to investigate relationship between the chemical structure and its biological activity, inhibition of mechanism, interaction of compounds, DNA binding constant and Gibbs free energy. Structural insights into inhibitor binding to the α-glucosidase and BuChE revealed significant contribution of hydrophobic regions and significant residues of active sites. Comparative molecular docking studies showed that the residues of oxyanion hole, catalytic triad and hydrophobic pocket were actively engaged in interaction with the inhibitor. DNA binding constant was found in the order Kb 3e > Kb 3c > Kb 3a > Kb 3b > Kb 3d, while Gibbs free energy was found in the order ?G 3e > ?G 3a > ?G 3b > ?G 3c > ?G 3d.
Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities
Madrid, Peter B.,Sherrill, John,Liou, Ally P.,Weisman, Jennifer L.,DeRisi, Joseph L.,Guy, R. Kiplin
, p. 1015 - 1018 (2007/10/03)
A simple two-step synthesis method was used to make 51 B-ring-substituted 4-hydroxyquinolines allowing analysis of the effect of ring substitutions on inhibition of growth of chloroquine sensitive and resistant strains of Plasmodium falciparum, the dominant cause of malaria morbidity. Substituted quinoline rings other than the 7-chloroquinoline ring found in chloroquine were found to have significant activity against the drug-resistant strain of P. falciparum W2.
