A novel diarylic ligand developed as chemosensor for the detection of M²⁺ was studied by density functional theory (DFT) and time-dependent DFT (TD-DFT). Geometries of the free-ligand and M²⁺-ligand complex were optimized at the CAM-B3LYP/631+G(d,p) level of theory in dimethyl sulfoxide using the conductor like polarizable continuum model. The adsorption spectra of these molecules were analyzed and compared with experimental data. The in
Theoretical study of structural, electronics and optical properties for these compounds allowed to understand the chemical changes that occurred in the ligand in the complexation process with the M⁺² ion.

In the present work a byphenyl hydrazone/SiO₂ composite was synthetized by a simple procedure. First, the mesoporous SiO₂ and the byphenyl hydrazone ligand were prepared. To synthetize the composite, the mesoporous silica and the ligand were dispersed in ethanol/water by a microwave assisted process. The composite was characterized by different techniques to evaluate its properties as chemosensor. The physicochemical characterization of the composite confirmed the selectivity and sensitive capacity to detect Cu⁺² ions.

At the beginning of the millennium, the (R,R)-HPA-12 was found to be the first antagonist of ceramide transporter CERT, which has been identified as a key factor for the ER-to-Golgi trafficking of ceramides. Ten years later, we have revised the stereochemistry of the most active HPA-12 diastereomer to (R,S) and developed synthesis of more potent alkyl substituted HPA-12 analogs. In the present study, based on the experience of our research group, the synthesis of the constrained pyrrolidine analogs of both (R,S)-HPA-12 and (R,R)-HPA-12 starting from substituted pyroglutamic acids easily accessible via our methodology will be demonstrated. The efficient synthesis of both target diastereoisomers of pyrrolidine HPA-12 analog included four key reactions. First was aza-Michael addition in tandem with CIAT - crystallisation induced asymmetric transformation, which yielded almost pure diastereomer and established an important stereogenic centre. Second reaction was stereoselective cyclisation, which also yielded almost pure diastereomer and introduced oxoproline structure in the molecule. Consequently, the target diastereomers were prepared by stereoselective reduction of oxo group and Mitsunobu inversion respectively. Configuration of stereogenic centre created by this reduction plays significant role in biological activity of pyrrolidine HPA-12 analogs and was confirmed by X-ray analysis. The samples of final derivatives were tested against inhibition of CERT protein. The results of the binding assays to the CERT protein will be discussed.

Porcupine is a protein belonging to the O-acyltransferase family, involved in catalyzing of palmitoylation of WNT proteins. WNT signalling has significant roles in many physiological functions, e.g.: hematopoiesis, homeostasis, neurogenesis, and apoptosis. Anomalous WNT signalling has been observed to be related to tumours generation, metabolic and neurodegenerative disorders. Therefore, compounds that inhibit this pathway are of great interest for the development of therapeutic approaches. For a better understanding of the common traits of such compounds, we have undertaken an in silico study in order to develop a valid ligand-based pharmacophore model based on a series of porcupine inhibitors. The best pharmacophore hypothesis found after the 3D QSAR validation process is represented by the following features: one hydrogen bond donor (D), three rings (R) and one hydrophobic centroid (H). The 3D-QSAR model obtained using the DRRRH hypothesis shows statistically significant parameters: correlation coefficients for the training set: R² of 0.90, and a predictive correlation coefficient for the test set, Q² of 0.86. The assessment of the pharmacophore model was also done by using the Enrichment calculator which provided very reliable metrics values (Receiver Operating Characteristic – ROC of 1; Robust Initial Enhancement – RIE of 17.97). Thereby, we obtained valuable results which can be further used in the virtual screening process for the discovery of new active compounds with potential anticancer activity.

A simple, rapid, precise and accurate HPTLC method was developed and validated for the estimation of Nintedanib, a novel tyrosine kinase inhibitor used in idiopathic pulmonary fibrosis, in bulk drug. Chromatography was carried out using silica gel 60 F₂₅₄ TLC plate and mobile phase Chloroform: Methanol in the ratio 7:3 v/v. The densitometric determination was done at 386 nm. Regression analysis data for the calibration plot were indicative of a good linear relationship between response and concentration over the range of 800-3200 ng/band. The variance (r) was found to be 0.999. The LOD & LOQ were found to be 83.357 ng/band & 252.599 ng/band respectively. The method was validated according to ICH Q2R1 guideline. The method was precise and accurate with %RSD 0.5323 (intraday) and 0.6939 (interday) respectively and percentage recoveries in the range 99.6459 % – 101.4298 %.

The use of hydrazone-type 1-azatriene derivatives for the synthesis of 3-methyl isoquinolines through a one pot microwave-assisted cyclization was developed and evaluated. The 1-azatrienes were generated by reaction of 2-propenylbenzaldehydes with hydrazines. Their subsequent electrocyclization gave rise to 3-methylisoquinolines, as well as to 3-methyl-3,4-dihydroisoquinolines as reaction by-products. The reaction conditions were optimized, and its scope and limitations were explored.

The reaction between aromatic and aliphatic aldehydes and ketones with methoxylamine is promoted by cerium chloride. The antifungal activity of some methoxime derivatives against five postharvest phytopathogenic fungi, was examined, employing imazalil and carbendazim as positive controls, and the preliminary results are discussed. The target fungi were Rhizopus stolonifer, Botrytis cinerea, Penicillium digitatum, Penicillium italicum and Monilinia fructicola. These phytopathogens affect fruits worldwide, causing relevant economic damage. In all cases, minimum inhibitory concentrations and minimum fungicidal concentrations were obtained. Despite most of the simple compounds resulted inactive, preliminary results suggest that certain compounds display a structure-dependent activity which correlates with the length of the substituent attached to the oxime sp² carbon.

A novel four-step methodology for the synthesis of 5-acyl- and 5-arylsulfonyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones, beta-oxoesters, or alpha-arylsulfonylketones followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-acyl- or 5-arylsulfonyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of strong bases, eliminate CHCl₃ to give the target compounds. The above methodology was also used in the synthesis of 5-acyl-1,2-dihydropyrimidin-2-imines starting from N-[(1-acetoxy-2,2,2-trichloro)ethyl]-N′-guanidine.

The reaction of 5-amino-3- (cyanomethyl) -1H-pyrazole-4-carbonitrile with 3-aryl-2,4-di(ethoxycarbonyl)-5-hydroxy-5-methylcyclohexanones in boiling acetic acid leads to the formation of new 4,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinazolines. The mechanism is discussed. The structure of the products was confirmed by means of ¹Н и ¹³С (DEPTQ) NMR, as well as 2D NMR (NOESY, ¹Н–¹³С HSQC, HMBC).

The reaction of 6-amino-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles with phosphorus sulfide in boiling pyridine leads to the formation of the unexpected [1,2]oxaphosphinino[6,5-c]pyrazoles. The structure of the products was confirmed by means of 2D NMR spectroscopy and X-ray analysis.