Naveen Shivalingegowda

Synthesis of novel 2-pyrazoline analogues with potent anti-inflammatory effect mediated by inhibition of phospholipase A2: Crystallographic, in silico docking and QSAR analysis

Oxidative-stress induces inflammatory diseases. Further, infections caused by drug-resistant microbial strains are on the rise. This necessitates the discovery of novel small-molecules for intervention therapy. A series of 3-(2,3-dichlorophenyl)-1-(aryl)prop-2-en-1-ones are synthesized as intermediates via Claisen-Schmidt reaction approach. Subsequently, these intermediates were transformed into 2-pyrazolines by their reaction with phenylhydrazine hydrochlorides in methanol and few drops of acetic acid under reflux conditions. Synthesized compounds were characterized by spectroscopic, crystallographic and elemental analyses studies and then, were evaluated for their in vitro antimicrobial and anti-inflammatory activities. Amongst the series, 3-(4-chlorophenyl)-5-(2,3-dichlorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (5e), 5-(2,3-dichlorophenyl)-3-(4-fluorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (5c) and 5-(2,3-dichlorophenyl)-3-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (5h) showed significant inhibition of phospholipase A2 with IC50 values of 10.2, 11.1 and 11.9µM, respectively. Protein structure modelling and docking studies indicated that the compounds showed binding to a highly conserved calcium-binding pocket on the enzyme. Further, compounds (5e), 1-(3-chlorophenyl)-5-(2,3-dichlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (5b), and 1-(3-chlorophenyl)-3-(4-chlorophenyl)-5-(2,3-dichlorophenyl)-4,5-dihydro-1H-pyrazole (5f) showed excellent antimicrobial activities against various bacterial and fungal strains. In conclusion, this study is a successful attempt at the synthesis and characterization of chalcone derivatives that can target phospholipase A2, an enzyme that is a prominent player in the physiological inflammatory cascade. Thus, these compounds show promise for development as next-generation nonsteroidal anti-inflammatory drugs.

Synthesis, structural characterization and biological properties of phosphorescent iridium(III) complexes

Two phosphorescent cyclometalated iridium(III)-triptycenyl-1,10-phenanthroline complexes [Ir(ppy)2(tpt-phen)]+ (1) and [Ir(bhq)2(tpt-phen)]+ (2) {ppy=2-phenylpyridine, bhq=Benzo[h]quinoline, tpt-phen=triptycenyl-1,10-phenanthroline} have been synthesized and structurally characterized. The structure of complex 2 has been studied by single crystal X-ray crystallography. The photophysical properties of complexes in a different solvent have also been investigated. The binding of complexes to the double stranded calf thymus (CT-DNA) has been investigated by spectroscopic techniques. These complexes condense originally circular plasmid DNA into particulate structures. The DNA-condensation induced by these complexes have been investigated by electrophoretic mobilty shift assay, dynamic light scattering, and fluorescence microscopy. Furthermore, the cytotoxicity of these complexes towards HeLa cells have been studied and their cellular localisation properties have been investigated by fluorescence microscopy.

Synthesis of cocrystals/salts of flucytosine: Structure and stability

5-Fluorocytosine or flucytosine (FLC) is a well-known drug for anti-fungal treatment and is one of the essential medicines needed in a health system. The main disadvantage of FLC drugs is their instability due to hydration under storage conditions. In the present work, cocrystal/salt screening experiments resulted in three molecular salts of FLC with dihydroxybenzoic acid derivatives, 2,3-dihydroxybenzoic acid (2,3HBA), 3,5-dihydroxybenzoic acid (3,5HBA), and 2,6-dihydroxybenzoic acid (2,6HBA), and two cocrystals with gallic acid (GAA) and glutaric acid (GLA). Since FLC drugs are highly susceptible to hydration, the present work concentrated on the stability of the synthesized molecular salts/cocrystals under different relative humidity (RH) conditions. All the newly formed crystalline adducts were characterized structurally, and the crystal structures were determined using single-crystal X-ray diffraction techniques (SCXRD). The FLC–2,6HBA salt was found to be a monohydrate, whereas the FLC–3,5HBA salt was crystallized as a hemipentahydrate. FLC–2,3HBA and FLC–GLA were crystallized in 2 : 1 equimolar ratios of FLC and the coformer. The FLC–GAA cocrystal crystallized in a 1 : 1 equimolar ratio. Two point heterosynthons between FLC and the coformer were observed in all the crystalline structures except FLC–GLA, where the structure was formed through a single point heterosynthon. Stability studies under different relative humidity conditions showed the non-hygroscopicity of the synthesized molecular salts/cocrystals. It was found that the FLC–2,3HBA salt, and the FLC–GAA and FLC–GLA cocrystals did not experience any hydration under the accelerated humidity conditions (both 70–75% RH and 90–95% RH) at ambient temperature (∼30 °C). However, FLC–2,6HBA and FLC–3,5HBA were found to be hygroscopic under 70–75% RH conditions. Furthermore, all the synthesized salts/cocrystals except FLC–3,5HBA were found to be stable for 2 months under ambient conditions (∼30 °C, 60–65% RH). Therefore, the FLC–2,3HBA salt, and the FLC–GAA and FLC–GLA cocrystals are better candidates for the preparation of new drug products of FLC.

Synthesis, characterization, X-ray diffraction studies and biological evaluation of tert-butyl 4-(2-ethoxy-2-oxoethyl)-piperazine-1-carboxylate and tert-butyl 4-(2-hydrazino-2-oxoethyl)piperazine-1-carboxylate

Two derivatives of N-Boc piperazine, an ester derivative, i.e., tert-butyl 4-(2-ethoxy-2-oxoethyl)-piperazine-1-carboxylate (1), and, a hydrazide derivative tert-butyl 4-(2-hydrazino-2-oxoethyl)piperazine-1-carboxylate (2) were synthesized and were characterized by FT-IR, 1H & 13C NMR and LCMS spectroscopic studies. The structures of both 1 and 2 were further confirmed by single crystal X-ray diffraction analysis. The molecule of 1 is linear in shape with the ethyl acetate moiety adopting fully extended conformation, while the molecule of 2 is L-shaped with the molecule being twisted at the C10 atom. The crystal structure of 1 adopts a two-dimensional zig-zag architecture featuring C–H…O intermolecular interactions, while that of 2 features strong N–H…O hydrogen bonds and intermolecular interactions of the type N–H…N and C–H…N, resulting in a two-dimensional structure. Furthermore, a detailed analysis of the intermolecular interactions and crystal packing of 1 and 2 via Hirshfeld surface analysis and fingerprint plots was performed. The antibacterial and antifungal activities of both the compounds have been studied against several microorganisms, and were found to be moderately active.

1,3-Bis[(E)-(3-bromobenzylidene)amino]propan-2-ol

1,3-Bis[(E)-(3-bromobenzylidene)amino]propan-2-ol Schiff base was synthesized in an acceptable yield by condensation of 3-bromobenzaldehyde with 1,3-diaminopropan-2-ol in methanol. The structure of the desired Schiff base compound was spectroscopically analyzed by EI-MS, CHN-elemental analysis, FT-IR, UV-visible, and 1H and 13C-NMR. The structure was also computed by DFT-optimization, MEP, Mulliken, NPA, IR- B3LYP/6-311++G(d), and SCF-TD-DFT.

Synthesis, spectral, biological activity, and crystal structure evaluation of novel pyrazoline derivatives having sulfonamide moiety

In the present study, synthesis and characterization of pyrazoline derivatives integrated with sulfonamide scaffold have been performed. The characterization of the molecules was done by elemental analysis, ultraviolet–visible, infrared, nuclear magnetic resonance (NMR), and mass spectra. Crystal structure of compounds 2e and 2g were determined by single crystal X-ray diffraction. In the compounds 2e and 2g, the intra molecular hydrogen bonds N15--H15…O13 and N14--H14…N1 were closed to form a S(6) ring motif, whereas the N14--H14…O17 hydrogen bond links, pairs of molecules related by inversion, forming the familiar R22(10) ring motif. The Hirshfeld surface analysis comprising of the dnorm surface plots, electrostatic potentials and two-dimensional fingerprint plots were generated in order to give visual confirmation of the intermolecular interactions. The molecules were screened for their in vitro antitubercular and antimicrobial activity. The molecules 2n and 2m have shown high potent against M. tuberculosis and most of the molecules have shown good potential against different bacteria and fungi.

Crystal structure of 3-(thiophen-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carboxamide

Abstract C15H15N3OS, monoclinic, P21/c (No. 14), a = 10.2852(5) Å, b = 10.1649(5) Å, c = 14.7694(8) Å, β = 107.442(2)°, V = 1473.12(13) Å3, Z = 4, Rgt(F) = 0.0449, wRref(F2) = 0.1275, T = 293(2) K.

Ultrasound-assisted synthesis of two novel [CuBr(diamine) 2 ·H 2 O]Br complexes: Solvatochromism, crystal structure, physicochemical, Hirshfeld surface thermal, DNA/binding, antitumor and antibacterial activities

Two new hydrated monocationic Cu(II) complexes with 1,3-propylenediamine and 1,2-ethylenediamine of general formula [CuBr(N-N)2·H2O]Br were prepared. The complexes were identified by means of several spectroscopic tools (Uv-visible, IR and MS), thermally (TG/DTA) and CHN-elemental analysis. The three dimensional structure for complex A and B was provide by X-ray diffraction studies and showed the Cu(II) ion as 4 + 1 + 1 coordinated, four nitrogen atoms of the diamine ligands, one bromide ion and one H2O semi-coordinated to the Cu(II) center, a typical trans effect is clearly observed in the two complexes. The molecular crystal structures are linked via several H-bonds like N_H…Br and N_H…O. Additionally, intra-molecular H-bonds of kind C_H…Br is observed; these interactions lead to crystal structure three dimensional architecture packing. Hirshfeld surfaces (HSA) analysis was served to figure out the inter-contacts and fingerprints atoms percentage. DNA-binding, antitumor and antibacterial effectiveness of the desired complexes were evaluated.

A fluorophore-labelled copper complex: crystal structure, hybrid cyclic water–perchlorate cluster and biological properties

A fluorophore-labelled copper(II) complex, aquabis(dimethylformamide-κO)(perchlorato-κO)[2-(quinolin-2-yl)-1,3-oxazolo[4,5-f][1,10]phenanthroline]copper(II) perchlorate monohydrate, [Cu(ClO4)(C22H12N4O)(C3H7NO)2(H2O)]ClO4·H2O, has been synthesized and characterized. A cyclic hydrogen-bonded water-perchlorate anionic cluster, i.e. [(ClO4)2(H2O)2]2-, has been identified within the structure. Each cyclic anionic cluster unit is interconnected by hydrogen bonding to the cation. The cations join into an infinite hydrogen-bonded chain running in the [010] direction. Furthermore, interaction of the complex with calf-thymus DNA (CT-DNA) and cellular localization within the cells was explored. Spectroscopic studies indicate that the compound has a good affinity for DNA and stains the nucleus of the cells.

DNA Binding Test, X-Ray Crystal Structure, Spectral Studies, TG-DTA, and Electrochemistry of [CoX2(dmdphphen)] (Dmdphphen Is 2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline, X = Cl, and NCS) Complexes

Two new neutral mixed-ligand cobalt(II) complexes, [CoCl2(dmdphphen)] 1 and [Co(NCS)2(dmdphphen)]  2, where dmdphphen is 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, were synthesized and characterized by an elemental analysis, UV-Vis, IR, TG/DTA, cyclic voltammetry CV, and single X-ray diffraction. Complex 2 crystallized as monoclinic with a space group P21/c. Co(II) ions are located in a distorted tetrahedral environment. TG/DTA result shows that these complexes are very stable and decomposed through one-step reaction. The two complexes exhibit a quasireversible one-electron response at −550 and 580 mV versus Cp2Fe/Cp2Fe+, which has been assigned to Co(I)/Co(II) and Co(II)/Co(III) couples. Absorption spectral studies reveal that such complexes exhibit hypochromicity during their interaction with CT-DNA.