P. Bhavana

Design, synthesis, physicochemical studies, solvation, and DNA damage of quinoline-appended chalcone derivative: comprehensive spectroscopic approach toward drug discovery.

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.

Nitrothienylporphyrins: Synthesis, crystal structure and, the effect of position and number of nitro groups on the spectral and electrochemical properties.

This article describes the investigation on the effect of orientation of the meso thienyl groups of porphyrins in deciding the site of nitration. The thienyl rings present at the meso position is found to be more susceptible for electrophilic nitration reaction than the pyrrole β-position in the molecules where there is a better conjugation between the thienyl rings and the porphyrin π-system. Signal corresponding to the imino hydrogens in the proton NMR spectrum of meso nitrothienylporphyrins get shifted to upfield with increase in the number of nitro groups on the porphyrin. This is also due to the extended conjugation of the porphyrins π-system with the meso thienyl rings. The above observations are also supported by the redox potentials of those compounds.

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

Inhibition 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 the absence and presence of BSA. Comparable ACE inhibitory mechanistic profile of ADMQ with standard drug captopril has been identified in terms of the 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 an aqueous buffer solution of BSA at a physiological pH of 7.4 contrary to the time resolved and FRET measurement where both the static and energy transfer mechanism co-exists. The rotationally restricted ADMQ molecule shows strong binding affinity towards subdomain IIA of site I with a close proximity (2.45 nm) to the Trp 213 residue. The minor decrease of α-helical content as calculated from CD spectral measurement and 1–3 A 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 the presence of BSA; however BSA shows lesser binding towards ADMQ in the presence of the target enzyme. The spectroscopic research described herein may provide enormously important information for ACE inhibition of the chalcone derivative and its detailed binding interaction with a carrier protein for chalcone based drug designing in medicinal chemistry research.

Groove binding mediated structural modulation and DNA cleavage by quinoline appended chalcone derivative

The present study embodies the detail DNA binding interaction of a potential bioactive quinoline appended chalcone derivative (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) with calf thymus DNA (ctDNA) and its consequences by UV-Vis absorption, steady state fluorescence spectroscopy, fluorescence anisotropy, circular dichromism, helix melting, agarose gel electrophoresis, molecular docking, Induced Fit Docking (IFD) and molecular dynamics (MD) simulation. The UV-Vis absorption and fluorescence study reveal that the molecule undergoes considerable interaction with the nucleic acid. The control KI quenching experiment shows the lesser accessibility of ADMQ molecule to the ionic quencher (I(-)) in presence of ctDNA as compared to the bulk aqueous phase. Insignificant change in helix melting temperature as well as in circular dichromism (CD) spectra points toward non-covalent groove binding interaction. The moderate rotational confinement of this chalcone derivative (anisotropy=0.106) trapped in the nucleic acid environment, the comparative displacement assay with well-known minor groove binder Hoechst 33258 and intercalator Ethidium Bromide establishes the minor groove binding interactions of the probe molecule. Molecular docking, IFD and MD simulation reveal that the DNA undergoes prominent morphological changes in terms of helix unwinding and bending to accommodate ADMQ in a crescent shape at an angle of 110° in a sequence specific manner. During interaction, ADMQ rigidifies and bends the sugar phosphate backbone of the nucleic acid and thereby shortens its overall length by 3.02Å. Agarose gel electrophoresis experiment with plasmid pBR 322 reveals that the groove binded ADMQ result in a concentration dependent cleavage of plasmid DNA into its supercoiled and nicked circular form. The consolidated spectroscopic research described herein provides quantitative insight into the interaction of a heterocyclic chalcone derivative with relevant target nucleic acid, which may be useful for the future research on chalcone based therapeutic agents.

(2E)-3-(4-Chloro­phen­yl)-1-(2,4-dimethyl­quinolin-3-yl)prop-2-en-1-one

Two independent molecules comprise the asymmetric unit of the title compound, C20H16ClNO, which differ in the orientation of the chalcone residue with respect to the quinoline ring [the C—C—C(=O)—C torsion angles are 69.5 (2) and 86.0 (2)°]. The configuration about each of the ethylene bonds [1.342 (2) and 1.338 (2) Å] is E. The three-dimensional crystal structure is stabilized by a combination of C—H⋯O, C—H⋯N, C—H⋯π interactions and π–π contacts between the independent molecules [Cg(C6 of quinoline)⋯Cg(C6 of quinoline) = 3.6719 (11) Å].

3-(4-Bromo-phen-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde.

In the title compound, C16H11BrN2O, the phenyl and chlorobenzene rings are twisted out of the mean plane of the pyrazole ring, forming dihedral angles of 13.70 (10) and 36.48 (10)°, respectively. The carbaldehyde group is also twisted out of the pyrazole plane [the C—C—C—O torsion angle is 7.9 (3)°]. A helical supramolecular chain along the b axis and mediated by C—H⋯O interactions is the most prominent feature of the crystal packing.

(2E)-1-(2,4-Dimethyl-quinolin-3-yl)-3-phenyl-prop-2-en-1-one.

Two independent molecules comprise the asymmetric unit of the title compound, C20H17NO, which differ in the orientation of the terminal phenyl ring with respect to the quinoline ring [the dihedral angles are 75.72 (11) and 84.53 (12)° for the two molecules]. The conformation about each of the ethylene bonds [1.329 (3) and 1.318 (3) Å] is E. The crystal structure features a combination of C—H⋯N, C—H⋯π and π–π contacts [inter-centroid between the phenyl ring and the quinoline benzene ring is 3.6024 (19) Å], generating a three-dimensional network.

[meso-5,10,15,20-Tetra­kis(5-bromo­thio­phen-2-yl)porphyrinato-κ4N,N′,N′′,N′′′]nickel(II)

The NiII atom in the title porphyrin complex, [Ni(C36H16Br4N4S4)], is in a square-planar geometry defined by four pyrrole N atoms. There is considerable buckling in the porphyrin ring with the dihedral angles between the N4 donor set and the pyrrole rings being in the range 17.0 (3)–18.8 (3)°. Each of the six-membered chelate rings is twisted about an Ni—N bond and the dihedral angles between diagonally opposite chelate rings are 13.08 (15) and 13.45 (11)°; each pair of rings is orientated in opposite directions. The bromothienyl rings are twisted out of the plane of the central N4 core with dihedral angles in the range 51.7 (2)–74.65 (19)°. Supramolecular chains along [001] are formed through C—H⋯Br interactions in the crystal packing. Three of the four bromothienyl units are disordered over two coplanar positions of opposite orientation with the major components being in 0.691 (3), 0.738 (3) and 0.929 (9) fractions.

1-(6,8-Dibromo-2-methyl­quinolin-3-yl)ethanone

Two independent molecules,1 and 2, with similar conformations comprise the asymmetric unit in the title compound, C12H9Br2NO. The major difference between the molecules relates to the relative orientation of the ketone–methyl groups [the C—C—C—C torsion angles are −1.7 (6) and −16.8 (6)° for molecules 1 and 2, respectively]; in each case, the ketone O atom is directed towards the ring-bound methyl group. The crystal packing comprises layers of molecules, sustained by C—H⋯O and π–π {ring centroid(C6) of molecule 2 with NC5 of molecule 1 [3.584 (3) Å] and NC5 of molecule 2 [3.615 (3) Å]} interactions. C—H⋯Br contacts also occur.

(2E)-1-(2,4-Dimethyl­quinolin-3-yl)-3-(thio­phen-2-yl)prop-2-en-1-one

Two independent but virtually identical molecules comprise the asymmetric unit in the title compound, C18H15NOS. With reference to the quinolin-3-yl group, the 3-(thiophen-2-yl)prop-2-en-1-one residue is almost perpendicular, with all but the carbonyl O atom lying to one side of the plane. This conformation is reflected by the C—C—C—C torsion angles of −102.2 (3) and 81.1 (3)° in the two independent molecules. The dihedral angle formed between the 13 non-H atoms directly associated with the quinolin-3-yl group and the thiophen-2-yl ring is 87.70 (11)° [83.85 (10)° for the second independent molecule]. The presence of C—H⋯O, C—H⋯N and π–π interactions [centroid–centroid distance = 3.5590 (12) Å] lead to supramolecular chains along the c-axis direction. These are connected along the a-axis direction by C—H⋯π interactions. The resultant supramolecular layers stack along the b axis.