One-pot and two-pot methods for chalcone derived pyrimidines synthesis and applications

Chalcone-derived pyrimidine is a well-known heterocyclic compound that is commonly present in ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) bio-isosteres. Pyrimidine derivatives are effective in both the electronic industry and drug industries. This review highlights the synthesis of pyrimidines, namely mono-pyrimidine, bis-pyrimidine, fused pyrimidine, symmetric, and asymmetric pyrimidine via one-pot and two-pot methods. The one-pot method is the direct reaction of amino derivatives with aldehydes and acetophenones, whereas the two-pot method is frequently reported for the synthesis of chalcone before the cyclization to a pyrimidine. This review is important in organic synthesis, particularly in the heterocyclic field, regarding pyrimidines and their significance in therapeutic and electronic industries.     

The Antiproliferative and Apoptotic Effect of a Novel Synthesized S-Triazine Dipeptide Series,and Toxicity Screening in Zebrafish Embryos

Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a—which contains morpholine, aniline, and glycylglycinate methyl ester—showed a high level of cytotoxicity against MCF-7 cells with IC₅₀ values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.     

Synthesis,Characterization and Photocatalytic Behavior of SiO2@nitrized-TiO2 Nanocomposites Obtained by a Straightforward Novel Approach

We report on the facile synthesis of SiO₂@nitrized-TiO₂ nanocomposite (NST) by calcination of TiO₂ xerogel with OctaAmmonium POSS® (N-POSS; POSS=polyhedral oligomeric silsesquioxanes). The as-obtained nanoporous mixed oxide is constituted by uniformly distributed SiO₂ and nitrized-TiO₂, where the silica component is present in an amorphous state and TiO₂ in an anatase/rutile mixed phase (92.1 % vs. 7.9 %, respectively) with very small anatase crystallites (3.7 nm). The TiO₂ lattice is nitrized both at interstitial and substitutional positions. NST features a negatively charged surface with a remarkable surface area (406 m² g⁻¹), endowed with special adsorption capabilities towards cationic dyes. Its photocatalytic behavior was tested by following the degradation of standard aqueous methylene blue and methyl orange solutions under UV and visible light irradiation, according to ISO 10678:2010. For comparison, analogous investigations were carried out on a silica-free N−TiO₂, obtained by using NH₄Cl as nitrogen source.     

Exploring the Potential of Multinuclear Solid-State 1H, 13C,and 35Cl Magnetic Resonance To Characterize Static and Dynamic Disorder in Pharmaceutical Hydrochlorides

Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch-to-batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field ³⁵Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: specifically, dynamic disorder occurring in duloxetine hydrochloride ( 1 ), static disorder in promethazine hydrochloride ( 2 ), and trifluoperazine dihydrochloride ( 3 ). In all structures, the presence of crystallographic disorder was confirmed by ¹³C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3 , ¹H solid-state NMR provided additional confirmation. Applying ³⁵Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3 , while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from ¹H, ¹³C, and ³⁵Cl NMR, we show that 3 exhibits a unique case of disorder involving the ⁺N−H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy three distinct sites.     

Polymer–polymer interactions via analog calorimetry. 3. Interaction between styrene and acrylonitrile repeat units

Analog calorimetry is used to study the interaction between styrene and acrylonitrile repeat units. Electrostatic charge calculations were used as a guide to divide the polymer repeat units and analogs into groups. A mean-field binary interaction model was used to evaluate group interaction energies. The enthalpic interaction energy for the styrene-acrylonitrile pair from this study is 7.63 ± 0.12 cal/cm³ which is consistent with values obtained from phase behavior studies of poly(styrene-co-acrylonitrile) blends. The cyano group, C(TRIPLE BOND)N, of the acrylonitrile repeat unit has a permanent dipole. The results of this study suggest that the orientation of this dipole with respect to the backbone of the acrylonitrile unit strongly affects its interaction with styrene repeat unit. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35: 831–839, 1997     

Polymer-Polymer interactions via analog calorimetry. 1—blends of polystyrene with poly(2,6-dimethyl-1,4-phenylene oxide)

Analog calorimetry is used as a tool to study the interaction of polystyrene, PS, with poly(2,6-dimethyl-1,4-phenylene oxide), PPO, and with poly(1,4-phenylene oxide). Electrostatic charge calculations were used as a guide to divide polymer repeat units and analogs into groups. A mean-field binary interaction model was used to cvaluate group interaction energies. The enthalpic interaction energy for the blend of PS-PPO obtained from this study is −1.35 ± 0.19 cal/cm₃, which is in good agreement with values obtained from neutron scattering. The results indicate that electronic rearrangements between the phenyl ring and substituted methyl groups in PPO have a large influence on the interaction with polystyrene. © 1996 John Wiley & Sons, Inc.     

Magnetically recoverable lanthanum hydroxide as an efficient catalyst for Aerobic Oxidative Conversions of primary alcohols to the nitriles

Herein we report a novel magnetically recoverable lanthanum hydroxide nanoparticles for oxidative synthesis of nitriles directly from corresponding alcohols with ammonia as nitrogen source. The procedure for the preparation and characterization of La(OH)₃/Fe₃O₄ magnetic nanoparticles were investigated and the scope and generality of the method was explored for a series of structurally diverse primary alcohols with electron‐donating and electron‐withdrawing groups. The best result was observed when 5 mol% of La with respect to the benzyl alcohol was used at reflux condition under O₂ atmosphere. The La(OH)₃/Fe₃O₄ magnetic nanoparticles could be easily isolated from the reaction mixture with an external magnet and reused at least 5 times without significant loss in activity.     

Quality variation and standardization of black pepper (Piper nigrum): A comparative geographical evaluation based on instrumental and metabolomics analysis

Black pepper (Piper nigrum; BP), known as the ‘king of spices’, imported from various countries is widely available in Saudi Arabian markets, as its demand as a food as well as a medicine for minor ailments is increasing in the country. However, there is a lack of appropriate information regarding these samples in terms of quality variation and standardization. We thus aimed to evaluate the quality and standardize the BP sample with respect to its physicochemical characters, active principle variation [i.e. piperine (PPN)], toxicity, and biological activity. The main focus is to validate whether any difference exists in the quality and quantity of active principle in these samples. For this purpose, physicochemical (chemical tests and ash values) and instrumental analyses [accelerated solvent extraction (ASE), ultra-high-pressure liquid chromatography (UHPLC)-diode array detector, infrared (IR), nuclear magnetic resonance (NMR), and inductively coupled plasma-MS (ICP-MS)] and biological evaluation {in vitro antioxidant activity [2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] and cytotoxicity assay} were performed. An extract yield (g) with %recovery of 2.26 ± 4.24 (11.3) was obtained for the Vietnamese sample, using a fast and rapid method of extraction (ASE). These values were 1.22 ± 2.64 (6.1) and 0.75 ± 1.69 (3.75) for the Pakistani and Indian samples. Physicochemical tests revealed the presence of flavonoids and phenolic compounds in all samples; however, in the Vietnamese sample a low amount of total, acid-insoluble, and high water-soluble ash value was noted. IR and NMR was applied to further standardize the samples. Results of ICP-MS analysis showed a high amount of macronutrients and micronutrients in the samples tested while UHPLC analysis revealed a high amount of PPN (ng/mL) in the Pakistani sample (1,362,614.09); these values were 1,051,848.04 and 768,512.81 for the Vietnamese and Indian samples, respectively. In vitro antioxidant and cytotoxicity activities revealed higher potential for the Vietnamese sample. The samples were properly standardized and effectively differentiated in terms of quality and biological activities using a fast and reliable method, however it certainly does not mean that a particular geographical region is more better or productive in terms of herbal products.     

Uniformly dispersed copper nanoparticles onto the modified magnetically recoverable nanocatalyst for aqueous synthesis of primary amides

Magnetically recoverable and environmentally friendly Cu‐based heterogeneous catalyst has been synthesized for the one‐pot conversion of aldehydes to their corresponding primary amides. The Fe₃O₄@SiO₂ nanocomposites were prepared by synthesis of Fe₃O₄ magnetic nanoparticles (MNPs) which was then coated with a silica shell via Stöber method. Bi‐functional cysteine amino acid was covalently bonded onto the siliceous shell of nanocatalyst. The Cu^II ions were then loaded onto the modified surface of nanocatalyst. Finally, uniformly dispersed copper nanoparticles were achieved by reduction of Cu^II ions with NaBH₄. Amidation reaction of aryl halides with electron‐withdrawing or electron‐donating groups and hydroxylamine hydrochloride catalyzed with Fe₃O₄@SiO₂@Cysteine‐copper (FSC‐Cu) MNPs in aqueous condition gave an excellent yield of products. The FSC‐Cu MNPs could be easily isolated from the reaction mixture with an external magnet and reused at least 8 times without significant loss in activity.     

Monoterpene Indole Alkaloids from the Aerial Parts of Rhazya stricta Induce Cytotoxicity and Apoptosis in Human Adenocarcinoma Cells

Chromatographic investigation of the aerial parts of the Rhazya stricta (Apocynaceae) resulted in the isolation of two new monoterpene indole alkaloids, 6-nor-antirhine-N₁-methyl (1) and razyamide (2), along with six known compounds, eburenine (3), epi-rhazyaminine (4), rhazizine (5), 20-epi-sitsirikine (6), antirhine (7), and 16-epi-stemmadenine-N-oxide (8). The chemical structures were established by various spectroscopic experiments. Compounds 1–8 exhibited cytotoxic effects against three cancer cells with IC₅₀ values ranging between 5.1 ± 0.10 and 93.2 ± 9.73 µM against MCF-7; 5.1 ± 0.28 and 290.2 ± 7.50 µM against HepG2, and 3.1 ± 0.17 and 55.7 ± 4.29 µM against HeLa cells. Compound 2 showed the most potent cytotoxic effect against all cancer cell lines (MCF-7, HepG2 and HeLa with IC₅₀ values = 5.1 ± 0.10, 5.1 ± 0.28, and 3.1 ± 0.17 µM, respectively). Furthermore, compound 2 revealed a significant increase in the apoptotic cell population of MCF-7, HepG2, and HeLa cells, with 31.4 ± 0.2%, 29.2 ± 0.5%, and 34.9 ± 0.6%, respectively. Compound 2 decreased the percentage of the phagocytic pathway on HepG2 cells by 15.0 ± 0.1%. These findings can explain the antiproliferative effect of compound 2.