The present study epitomizes the design, synthesis, photophysics, solvation, and interaction with calf-thymus DNA of a potential antitumor, anticancer quinoline-appended chalcone derivative, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) using steady state absorption and fluorescence spectroscopy, molecular modeling, molecular docking, Fourier-transform infrared spectroscopy (FTIR), molecular dynamics (MD) simulation, and gel electrophoresis studies. ADMQ shows an unusual photophysical behavior in a variety of solvents of different polarity. The dual emission has been observed along with the formation of twisted intramolecular charge transfer (TICT) excited state. The radiationless deactivation of the TICT state is found to be promoted strongly by hydrogen bonding. Quantum mechanical (DFT, TDDFT, and ZINDO-CI) calculations show that the ADMQ is sort of molecular rotor which undergoes intramolecular twist followed by a complete charge transfer in the optimized excited state. FTIR studies reveals that ADMQ undergoes important structural change from its native structure to a β-hydroxy keto form in water at physiological pH. The concentration-dependent DNA cleavage has been identified in agarose gel DNA electrophoresis experiment and has been further supported by MD simulation. ADMQ forms hydrogen bond with the deoxyribose sugar attached with the nucleobase adenine DA-17 (chain A) and result in significant structural changes which potentially cleave DNA double helix. The compound does not exhibit any deleterious effect or toxicity to the E. coli strain in cytotoxicity studies. The consolidated spectroscopic research described herein can provide enormous information to open up new avenues for designing and synthesizing chalcone derivatives with low systematic toxicity for medicinal chemistry research.

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.

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