Design,Synthesis, Pharmacodynamic and In Silico Pharmacokinetic Evaluation of Some Novel Biginelli-Derived Pyrimidines and Fused Pyrimidines as Calcium Channel Blockers

Some new pyrimidine derivatives comprising arylsulfonylhydrazino, ethoxycarbonylhydrazino, thiocarbamoylhydrazino and substituted hydrazone and thiosemicarbazide functionalities were prepared from Biginelli-derived pyrimidine precursors. Heterocyclic ring systems such as pyrazole, pyrazolidinedione, thiazoline and thiazolidinone ring systems were also incorporated into the designed pyrimidine core. Furthermore, fused triazolopyrimidine and pyrimidotriazine ring systems were prepared. The synthesized compounds were evaluated for their calcium channel blocking activity as potential hypotensive agents. Compounds 2, 3a, 3b, 4, 11 and 13 showed the highest ex vivo calcium channel blocking activities compared with the reference drug nifedipine. Compounds 2 and 11 were selected for further biological evaluation. They revealed good hypotensive activities following intravenous administration in dogs. Furthermore, 2 and 11 displayed drug-like in silico ADME parameters. A ligand-based pharmacophore model was developed to provide adequate information about the binding mode of the newly synthesized active compounds 2, 3a, 3b, 4, 11 and 13. This may also serve as a reliable basis for designing new active pyrimidine-based calcium channel blockers.     

Silica-Derived Nanostructured Electrode Materials for ORR,OER, HER,CO2RR Electrocatalysis,and Energy Storage Applications: A Review**

Silica-derived nanostructured catalysts (SDNCs) are a class of materials synthesized using nanocasting and templating techniques, which involve the sacrificial removal of a silica template to generate highly porous nanostructured materials. The surface of these nanostructures is functionalized with a variety of electrocatalytically active metal and non-metal atoms. SDNCs have attracted considerable attention due to their unique physicochemical properties, tunable electronic configuration, and microstructure. These properties make them highly efficient catalysts and promising electrode materials for next generation electrocatalysis, energy conversion, and energy storage technologies. The continued development of SDNCs is likely to lead to new and improved electrocatalysts and electrode materials. This review article provides a comprehensive overview of the recent advances in the development of SDNCs for electrocatalysis and energy storage applications. It analyzes 337,061 research articles published in the Web of Science (WoS) database up to December 2022 using the keywords “silica”, “electrocatalysts”, “ORR”, “OER”, “HER”, “HOR”, “CO₂RR”, “batteries”, and “supercapacitors”. The review discusses the application of SDNCs for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), carbon dioxide reduction reaction (CO₂RR), supercapacitors, lithium-ion batteries, and thermal energy storage applications. It concludes by discussing the advantages and limitations of SDNCs for energy applications.     

Novel Nano‐sized bis‐indoline Derivatives as Antitumor Agents

A facile access to novel bis‐(indoline‐2,3‐dione) was achieved via reactions of isatin with 1,3‐dibromopropane. The utility of the versatile bis‐(indoline‐2,3‐dione) in the design of new multifunctional building blocks using condensation with hydrazine derivatives was demonstrated. Moreover, a new series of bis‐thiazoles and bis‐thiazol‐4(5H)‐ones were synthesized by the reaction of bis‐thiosemicarbazone derivative with various derivatives of hydrazonoyl halides. The calculations derived from X‐ray diffraction patterns indicated the nanosize of the newly designed compounds. The spectral data of the formed compounds were established their structures. Also, the cytotoxic activity of the produced derivatives was screened against line MCF‐7 (breast cancer cell). It was found that four derivatives from nine investigated compounds showed activity more potent than the standard drug used by 20 times in some cases.     

The Fluorescent Effect of Withania Somnifera Chitosan Nanocomposite as an Effective Contrast Agent for Cancer Theragnostic: Experimental Study in Vitro

Journal of Fluorescence - Nanomedicine and fluorescent optical imaging are effective in early cancer detection. The current study synthesized biocompatible nanocomposites from natural biomaterials...     

Synthesis,Characterization, and Anticancer Screening of Some New Bithiazole Derivatives

Russian Journal of Organic Chemistry - Twenty new bithiazole derivatives were synthesized by condensation of...     

Characterization of new Co(II) complexes and photographic monitoring for their toxic impact on breast cancer cells according to simulation study

Five new nitrogen-rich ligands (thioanhydrides) were synthesized and fully characterized. Then, their corresponding Co(II) complexes were prepared and also elucidated by analytical and spectral conformational techniques. First of all, the mono-negative tri-dentate mode was proposed with all derivatives towards mono-nuclear central atom. According to ligand field transitions and magnetic susceptibility values, the square-planar as well as octahedral geometries were the forms suggested. The presence of water molecules was investigated thermally. For conformational implementation under optimal conditions, energy minimization was carried out and fundamental data were obtained and studied. In silico investigation was carried out using the MOE docking approach to predict the inhibition activity for the new compounds. The Co(II)– 3e complex played an excellent inhibitory role. After that and based on preliminary results, in vitro antitumor screening against MCF-7 cell line was conducted for all Co(II) complexes. The results were consistent with that for standard drug (doxorubicin), and the inhibition feature for the complexes was ranked. Through photographic monitoring, outstanding inhibition activity towards breast cancer spreading was recorded for the Co(II)– 3e complex, which coincides well with MOE docking data.     

Synthesis and biological activity of new 1H‐Pyrazolo[3,4‐b]quinoxalines (flavazoles)

A novel series of flavazoles 3a‐1 were synthesized via dehydrative cyclization of a new series of 3‐[(α‐arylhydrazono)‐aroylmethyl]quinoxalin‐2(1H)‐ones 2a‐1 and their biological activity has been evaluated. The tautomeric structure of the precursors 2a‐1 has also been elucidated.     

Synthesis and tautomeric structure of 3,7-bis(arylazo)-6-methyl-2-phenyl-1H-imidazo[1,2-b]pyrazoles in ground and excited states

Three series of 3,7-bis(arylazo)-6-methyl-2-phenyl-1H-imidazo-[1,2-b]pyrazoles were prepared starting from N-aryl 2-oxo-2-phenylethanehydrazonoyl bromides and 5-amino-4-arylazo-3-methyl pyrazoles. The acid dissociation constants pK and pK^* in both the ground and excited states, respectively, were determined and correlated with the Hammett equation. The results of such correlations together with the spectroscopic data indicated that the title compounds exist predominantly in the 1H-bis(arylazo) form in both ground and excited states.     

Synthesis of antimicrobial azoloazines and molecular docking for inhibiting COVID-19

Diverse new azoloazines were synthesized from the reaction of fluorinated hydrazonoyl chlorides with heterocyclic thiones, 1,8-diaminonaphthalene, ketene aminal derivatives, and 4-amino-5-triflouromethyl-1,2,4-triazole-2-thiol. The mechanistic pathways and the structures of all synthesized derivatives were discussed and assured based on the available spectral data. The synthesized azoloazine derivatives were evaluated for their antifungal and antibacterial activities through zone of inhibition measurement. The results revealed promising antifungal activities for compounds 4 , 5 , 17a , b , 19 , and 25 against the pathogenic fungal strains used; Aspergillus flavus and Candida albicans compared to ketoconazole. In addition, compounds 4 , 5 , 19 , and 25 showed moderate antibacterial activities against most tested bacterial strains. Molecular docking studies of the promising compounds were carried out on leucyl-tRNA synthetase active site of Candida albicans, suggesting good binding in the active site forming stable complexes. Moreover, docking of the synthesized compounds was performed on the active site of SARS-CoV-2 3CLpro to predict their potential as a hopeful anti-COVID and to investigate their binding pattern.     

Synthesis, reactions, and biological activity of 1,4-benzothiazine derivatives

Abstract  

6,7-Dimethoxy-2H-1,4-benzothiazin-3(4H)-one reacts with dimethylformamide dimethylacetal (DMF-DMA) to give the novel enaminone 2-(dimethylaminomethylene)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-one. The reaction of the latter with various active methylene compounds afforded pyrido[3,2-b][1,4]benzothiazines. Also, coupling of the enaminone with diazotized aniline derivatives gave 2-(arylhydrazono)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-ones. Spectral data indicated that the latter compounds exist predominantly in the hydrazone tautomeric form. In addition, coupling of the enaminone with diazotized heterocyclic amines afforded tetra- and pentaheterocyclic ring systems. The antitumor and antimicrobial activity of some of the synthesized compounds was screened.