In Vivo and In Vitro Biological Evaluation and Molecular Docking Studies of Compounds Isolated from Micromeria biflora (Buch. Ham. ex D.Don) Benth

Micromeria biflora, a traditional medicinal plant, is extensively used for treating various painful conditions, such as nose bleeds, wounds, and sinusitis. A phytochemical investigation of the chloroform fraction of Micromeria biflora led to the isolation of salicylalazine. Salicylalazine was assessed in vivo for analgesia, muscle relaxation, sedative, and anti-inflammatory properties, as well as in vitro for COX-1/2 inhibition activities. It was assessed against a hot plate-induced model at different doses. The muscle relaxant potential of salicylalazine was evaluated in traction and inclined screening models, while sedative properties were determined using an open-field model. The anti-inflammatory potential of salicylalazine was assessed in histamine and carrageenan-induced paw edema screening models. Salicylalazine exhibited significant analgesic potential in a dose-dependent manner. In both screening models, an excellent time-dependent muscle-relaxation effect was observed. Salicylalazine demonstrated excellent sedation at high doses. Its anti-inflammatory activity was determined through the initial and late phases of edema. It exhibited anticancer potential against NCI-H226, HepG2, A498, and MDR2780AD cell lines. In vitro, salicylalazine showed preferential COX-2 inhibition (over COX-1) with an SI value of 4.85. It was less effective in the initial phase, while, in the later phase, it demonstrated significant effects at 15 and 20 mg/kg doses compared with the negative control. Salicylalazine did not exhibit cytotoxicity in the MTT assay, preliminarily indicating its safety.     

In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense

This study reports the isolation of three new C₂₀ diterpenoid alkaloids, Chitralinine A–C (1–3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1–3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC₅₀ value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol⁻¹ for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease.     

Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box–Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity.     

Synthesis and Theoretical Study of Novel Imidazo[4,5-b]pyrazine-Conjugated Benzamides as Potential Anticancer Agents

Russian Journal of Organic Chemistry - A green synthetic protocol has been developed for the synthesis of imidazo[4,5-b]pyrazine-conjugated benzamides in 80–85% yield via one-pot...     

Kumada Cross Coupling Reaction for the Synthesis of Quinazoline Derivatives,Evaluation of Their Antibacterial Activity and Docking Studies

Russian Journal of General Chemistry - A series of C7-substituted-2-morpholino-N-(pyridin-2-ylmethyl)quinazolin-4-amine derivatives 3a–3t were synthesized by using Nickel catalyzed Kumada...     

Absolute Quantification of Follicle Stimulating Hormone (FSH) Using Its Signature Peptides and Enzymatic Digestion in Human Serum by UPLC/LC–MS/MS

Chromatographia - In vitro quantification of follicle stimulating hormone (a Macroheterogeneity protein) in human serum using mass spectrometry is challenging and as yet unreported due to its...     

Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity

Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]⁶-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them achieved enhanced AT₂R/AT₁R subtype selectivity. This diversification has been studied through 2D NMR spectroscopy and unveiled a putative more structured microenvironment for the two selective ligands accompanied with increased number of NOE cross-peaks. The most potent analogue, compound 2 , has been explored regarding its neurotrophic potential and resulted in an enhanced neurite growth with respect to the established agent C21.     

Facile Reduction of β-Enamino Oxopyrrolidine Carboxylates Mediated by Heterogeneous Palladium Catalyst

Russian Journal of Organic Chemistry - The synthesis of diastereoisomers via diastereoselective hydrogenation of unreactive endocyclic enamine system of ethyl 4-hydrazinyl- and...     

An efficient and convenient route for the synthesis of thiophene-2-carboxamidines as potential inhibitors of nitric oxide synthase (NOS)

A mild and efficient synthesis of substituted thiophene-2-carboxamidines which are potent inhibitors of nitric oxide synthase (NOS) is reported herein. The key step involves reaction of a BOC-protected imidazolyl thiophene-2-carboxamidine reactive intermediate with various primary amines to form BOC-thiophene-2-carboxamidines which could be readily deprotected using TFA to furnish free carboxamidines. The method is very mild and tolerates diverse substituents including sensitive peptide and amino acid fragments. This new methodology represents a substantial improvement to the literature method owing to its simplicity and hassle-free purification procedures.     

Photocatalytic Studies of La,Ce Co-Doped ZnO Nanoparticles

Russian Journal of Applied Chemistry - Zinc oxide nanoparticles were co-doped with varying concentrations of lanthanum (La) and cerium (Ce) ions using co-precipitation method. The resulting powders...