Development and Validation of a Stability-Indicating High-Performance Thin-Layer Chromatographic Method for Determination of Pyridostigmine Bromide in the Presence of Its Alkaline-Induced Degradation Product

JPC – Journal of Planar Chromatography – Modern TLC - A validated, sensitive, and highly selective stability-indicating high-performance thin-layer chromatographic (HPTLC) method has...     

Synthesis,reactions, and antimicrobial activity of some novel pyrazolo[3,4-d]pyrimidine,pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives

Treatment of N-phenyl-substituted benzenecarbo-hydrazonoyl chlorides 1a - d with malononitrile in sodium ethoxide solution gave 5-amino-4-cyanopyrazole derivatives 2 - 5 . Compounds 2 - 5 were converted to formidate derivatives 6 - 9 upon treatment with TEOF in acetic anhydride. The reaction of the latter products 6 - 9 with hydrazine hydrate gave imino-amino derivatives 10 - 13 , which was converted to hydrazino derivatives 14 - 17 by refluxing with hydrazine hydrate. Hydrazino as well as imino-amino derivatives undergo condensation, cyclization, and cycloaddition reactions to give pyrazolo[3,4-d]pyrimidine 18 - 21 , pyrazolo[4,3-e][1,2,4]triazolo-[3,4-c]pyrimidine 22 - 27 , and pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazine 42 - 44 derivatives. Antimicrobial studies are performed using two Gram-positive bacteria and two Gram-negative bacteria. Data indicated that compounds 5 , 28D , 29B , and 31D are exploring elevated antibacterial effects against all strains tested. Compound 28D is the most promising antibacterial agent against the delicate bacterial strain Bacillus subtilis and Pseudomonas aeruginosa with high effectiveness (low minimum inhibitory concentration [MIC] value) 40 and 60 μg/mL, respectively.     

Antitumor,cytotoxic, and antioxidant evaluation of six heterocyclic compounds containing different heterocycle moieties

Heterocyclic compounds with different heterocycle moieties, namely benzoxazinone, benzimidazole, quinazolinone, and benzofuranone heterocyclic rings, were synthesized, characterized, and evaluated for their anticancer activity against human hepatocellular carcinoma cell line (HepG2) using sulforhodamine B (SRB) and dimethylthiazol-diphenyltetrazolium bromide (MTT) assays. Also, their cytotoxic activities were tested against human epithelioid carcinoma (Hela) cell line in comparison with normal cell, amniotic epithelial (WISH) cell line, as an in vitro toxicity estimation model. The results showed clearly that 2-(2-benzyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide 4 is the most potent antioxidant and anticancer agents. Although, 3-amino-2-benzylquinazolin-4(3H)-one 5 is less potent anticancer agent against Hela but it is more safe against normal cell (WISH).     

Electronic structure and energy decomposition of binuclear transition metal complexes containing β-diketiminate and imido ligands: spin state and metal’s nature effects

DFT calculations with full geometry optimization using BP86-D and OPBE functionals have been performed on series of [(BDI)M(NH)]₂(Bz) and [(BDI)M(NH)]₂(Tol) (M = Ti, V, Nb, Cr, Mn, Fe, Co, and Ni; BDI = β-diketiminate; NH = imido group; Bz = benzene; and Tol = toluene) of various spin states (singlet S = 0, triplet S = 1, quintet S = 2, and singlet S = 0 of broken symmetry method). Depending on the metal nature and its electron count and the spin state, the six-membered ring in [(BDI)M(NH)]₂(Bz) and [(BDI)M(NH)]₂(Tol) adopts various hapticities that involve full or partial coordination, giving rise to a flat or a distorted ring, respectively. The NH^2? imido group is linear or bent with respect to its sp or sp² hybridization acting as a six- or a four-electron donor, respectively. The (BDI)^? anion is a bidentate ligand as a six-electron donor. The optimized geometries do not show direct metal-metal bonding and correspond to long separations. The optimized structures for Nb metal are comparable to the available experimental ones. The Ziegler-Rauk energy decomposition analysis scheme was employed to characterize the geometry distortion, the steric interaction (electrostatic and Pauli), and the orbital interaction terms in the total bonding energy. The results showed that the interaction terms in all the studied complexes are governed by one third covalent and two thirds ionic characters, which are in agreement with the ΔE_elstat (electrostatic) and ΔE_orb (orbital) contributions, respectively, into the total attractive interaction (ΔE_elstat + ΔE_orb).     

Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of −8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.     

Determination of the Kinetic and Thermodynamic Parameters of Adsorption Processes by a Volume Step Thermal Method

A volume step method measuring the pressure and the adsorbent temperature of an adsorbent-adsorbate system has been developped. It is shown that this method allows the determination of all the relevant parameters of an adsorption process, kinetic as well as thermodynamic in case of Linear Driving Force mass transfer. The method for determining the parameters can be extended to the case of diffusive mass transfer if the mass transfer kinetics is faster than the heat transfer kinetics. An example is given, showing the determination of the diffusion coefficient of carbon dioxide in NaX zeolite pellets and the change of the diffusion coefficient and of the isosteric heat of adsorption when the adsorbent is not fully dehydrated.     

Recent Developments in the Photochemical Synthesis of Functionalized Imidazopyridines

Imidazopyridines constitute one of the most important scaffolds in medicinal chemistry, as their skeleton could be found in a myriad of biologically active molecules. Although numerous strategies were elaborated for imidazopyridine preparation in the 2010s, novel eco-compatible synthetic approaches have emerged, conscious of climate change concerns. In this framework, photochemical methods have been promoted to conceive this heterocyclic motif over the last decade. This review covers the recently published works on synthesizing highly functionalized imidazopyridines by light induction.     

Notes on the convergence order of gradient schemes for time fractional differential equations

We apply the GDM (Gradient Discretization Method), developed recently, as discretization in space to time-fractional diffusion and diffusion-wave equations with a fractional derivative of Caputo type in any space dimension.In the case of time-fractional diffusion equations, we establish an implicit scheme, and we prove an $L^{\infty }(L^2)$-error estimate. A similar result in a discrete $L^{\infty }(H_0^1)$–norm is also stated.To construct the numerical scheme for the time-fractional diffusion-wave equation, we write the equation in the form of a system of two low-order equations. We state an a prior estimate result that helps us to derive error estimates in discrete semi-norms of $L^{\infty }(H^1)$ and $H^1(L^2)$. The convergence is unconditional. Another gradient scheme is also suggested. We state its convergence results, which improve the convergence order proved recently for a SUSHI scheme.These results hold then for all the schemes within the framework of GDM: conforming and nonconforming finite element, mixed finite element, hybrid mixed mimetic family, some Multi-Point Flux approximation finite volume schemes, and some discontinuous Galerkin schemes.