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.

2D/1D MoS2 /TiO2 Heterostructure Photocatalyst with a Switchable CO2 Reduction Product.

Regulating the transfer pathway of charge carriers in heterostructure photocatalysts is of great importance for selective CO2 photoreduction. Herein, the charge transfer pathway and in turn the redox potential succeeded to regulate in 2D MoS2 /1D TiO2 heterostructure by varying the light wavelength range. Several in situ measurements and experiments confirm that charge transfer follows either an S-scheme mechanism under simulated solar irradiation or a heterojunction approach under visible light illumination, elucidating the switchable property of the MoS2 /TiO2 heterostructure. Replacing the simulated sunlight irradiation with the visible light illumination switches the photocatalytic CO2 reduction product from CO to CH4. 13 CO2 isotope labeling confirms that CO2 is the source of carbon for CH4 and CO products. The photoelectrochemical H2 generation further supports the switching property of MoS2 /TiO2 . Unlike previous studies, density functional theory calculations are used to investigate the band structure of Van der Waals MoS2 /TiO2 S scheme after contact, allowing to propose accurate charge transfer pathways, in which the theoretical results are well matched with the experimental results. This work opens the opportunity to develop photocatalysts with switchable charge transport and tunable redox potential for selective artificial photosynthesis.