Antihypertensive activity of a quinoline appended chalcone derivative and its site specific binding interaction with a relevant target carrier protein

Abstract

The usefulness of heterocyclic chalcone derivative as a therapeutic target in controlling hypertension and its site specific binding interaction with model transport protein to get a clear picture about its delivery mechanism. AbstractInhibition of Angiotensin Converting Enzyme (ACE) is identified as a main therapeutic target in controlling hypertension. The principal intent of this work is to investigate the ACE inhibitory property of a quinoline appended chalcone derivative (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ), and its binding mechanism with model transport protein BSA by employing steady state and time resolved fluorescence, Circular Dichroism (CD), in silico Molecular Docking, Induced Fit Docking (IFD) and Molecular Dynamics (MD) simulation. Incubation of ADMQ with kidney cortex plasma membrane shows considerable antihypertensive effect by the inhibition of ACE. ADMQ undergoes strong interaction with ACE both in absence and presence of BSA. Comparable ACE inhibitory mechanistic profile of ADMQ with standard drug captopril has been identified in terms of ligand interaction pattern, changes in secondary structural elements and protein RMSF. The steady state emission of BSA undergoes a remarkable decrement via ground state complex formation upon addition of ADMQ in aqueous buffer solution of BSA at physiological pH 7.4 contrary to the time resolved and FRET measurement where both the static andenergy transfer mechanism co-exists. Rotationally restricted ADMQ molecule shows strong binding affinity towards subdomain IIA of site I with a close proximity (2.45 nm) of the Trp 213 residue. The minor decrease of α-helical content as calculated from CD spectral measurement and 1-3 Å change in protein RMSD during MD simulation clearly indicate that the polypeptide chain is partially destabilized due to the above site specific accommodation of the host (ADMQ). A slight diminution in the ACE inhibitory profile is observed in presence of BSA; however BSA shows lesser binding towards ADMQ in presence of the target enzyme. The spectroscopic research described herein may provide enormous important information for ACE inhibition of chalcone derivative and its detail binding interaction with carrier protein for the chalcone based drug designing in medicinal chemistry research.

Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach

“…Several commercial drugs such as Primaquine ® , Plasmoquine ® , Mefloquine ® , Chloroquine ® , OSI-930, and Saquinavir ® incorporate quinoline pharmacophore [ 14 , 15 ]. A range of quinoline derivatives have been reported for their analgesic [ 16 ], antifungal [ 17 ], antibacterial [ 18 ], antioxidant [ 19 ], anticancer [ 20 , 21 ], anti-inflammatory [ 22 ], antiviral [ 23 , 24 ], anti-Alzheimer [ 25 ], cytotoxic [ 26 ], antileishmanial [ 27 , 28 ], and anti-hypertensive activities [ 29 , 30 ]. Similarly, piperidine ring is also prevalent in numerous naturally occurring alkaloids [ 31 ].…”

Motion‐Induced Changes in Emission as an Effective Strategy for the Ratiometric Probing of Human Serum Albumin and Trypsin in Biological Fluids

“…Furthermore, changes in the CD signals of the protein upon incubation with different amounts of compound 1 showed a perturbation in the α‐helical structure of the protein template (Figure c), which suggested that the probe molecule had become embedded in the α‐helices of subdomain IIA of HSA . FTIR analysis also revealed that stretching frequencies related to the α‐helices of the protein (amide I, OH, and NH bands) were affected during the interaction with compound 1 (see the Supporting Information, Figures S13 and S14) …”

“…[55,56] FTIR analysisa lso revealed that stretching frequencies related to the a-helices of the protein (amide I, OH, and NH bands) were affected during the interaction with compound 1 (see the Supporting Information, Figures S13 and S14). [57,58] Because pH value had ap ronounced influence on the assembly behavior of compound 1,w ea lso investigated the effect of pH value on its albumin-sensing properties. The emission spectrum of compound 1 at pH 6.0 clearly showed aggregate emission, with am aximum at l = 454 nm.…”

An efficient 3-acylquinoline synthesis from acetophenones and anthranilviaC(sp3)–H bond activation mediated by Selectfluor

“…3-Acylquinolines have been reported to possess herbicidal activity 46 as well as antihypertensive activity. 47 Some efficient methods for the preparation of 3-acylquinolines have been developed, such as Pd-catalyzed carbonylative Suzuki crosscoupling reactions of arylboronic acid with 3-iodoquinoline, 48 Pd-catalyzed coupling of aldehydes and 3-bromoquinoline 49 or arylboronic acid and 3-quinolinecarbaldehyde, 50 Fe-catalyzed cascade Michael addition/cyclization of o-aminoaryl aldehydes/ketones/alcohols with ynones, 45 and domino reactions between N,N-dimethyl enaminones and anilines. 41 In addition, dehydrogenation of saturated carbonyl compounds to afford a,b-unsaturated carbonyl derivatives has been found to be compatible with other organic transformations, leading to efficient one-pot protocols for the synthesis of functionalized molecules.…”