Synthesis,in vitro antimicrobial assessment,and computational investigation of pharmacokinetic and bioactivity properties of novel trifluoromethylated compounds using in silico ADME and toxicity prediction tools

1,3-Dipolar cycloaddition reactions of a sugar-based trifluoromethylated nitrone-to-maleimide and allyl bromide afforded a series of cycloadducts in good yield. The same nitrone reacts with propargyl acetate lead, after rearrangement of 4-isoxazoline, to aziridine with good yield. The obtained compounds were evaluated for their in vitro antimicrobial potency. Additionally, we are interested in predicting their physicochemical parameters such as lipophilicity and bioactivity score as well as their pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) such as plasma protein binding (PPB) penetration of the blood–brain barrier (BBB), human intestinal absorption (HIA), cellular permeability (PCaco-2), cell permeability of Madin–Darby canine kidney (PMDCK), P-glycoprotein (P-gp) efflux, CYP inducers, substrates and inhibitors’ skin and permeability (PS), and their toxicological behavior [mutagenicity, carcinogenicity, acute, environmental, cardiotoxicity (hERG inhibition)] using in silico computational methods. Also, we aimed to validate QSAR models for the elucidation of their antitarget using 32 sets of end-points (IC50, Ki and Kact). The obtained result provides good information about the pharmacotherapy potential and toxicity of the examined molecules with good compliance between in vitro antimicrobial and the predicted properties. Findings indicated and encouraged the use of these compounds and their derivatives for further in vivo evaluations in the design and the elucidation of the intrinsic mechanisms as well as the efficacy of the selected powerful drug.     

Boundary null-controllability of linear diffusion–reaction equations

This Note deals with the boundary null-controllability of linear diffusion–reaction equations in a 2D bounded domain. We transform the determination of the sought HUM boundary control into the minimization of a continuous and strictly convex functional. In the case of a rectangular domain where the diffusion tensor is represented by a diagonal matrix, we establish a procedure based on the inner product method that uses a complete orthonormal family of Sturm–Liouville's eigenfunctions to express explicitly the sought control.     

Rigid tetranitroresorcinarenes

[reaction: see text]. o-alkylation of C2V-symmetrical resorcinarene tetraesters 2 with 2 equiv of 1,3-difluoro-4,6-dinitrobenzene readily affords conformationally rigid octanitro resorcinarene 3, which is a potential scaffold for the design of supramolecular structures.     

When Is a Sum of Partial Reflections Equal to a Scalar Operator?

We describe the set of values of the parameter for which there exists a Hilbert space H and n partial reflections A ₁,...,A _n (self-adjoint operators such that A _k ³ =A_k or, which is the same, self-adjoint operators whose spectra belong to the set {-1,0,1}) whose sum is equal to the scalar operator I _H .     

Amino Acid Derivatives,VII [1]: Synthesis and Antiviral Evaluation of α-Amino Acid Esters Bearing an Indazole Side Chain

Summary. A series of peptide and dipeptide derivatives conjugated with an indazole residue were synthesized. The new compounds were evaluated in vitro for cytotoxicity against Hepatitis-A virus (HAV-27), Herpes Simplex virus-1 (HSV-1), and Hepatitis-B virus (HBV) and showed moderate to high activity.     

Equilibrium and hydrolysis ofα-amino acid esters in ternary complexes of copper(II) involving glycyl-L-tyrosine

Summary Binary and ternary complexes of copper(II) with glycyl-L-tyrosine and an amino acid ester were investigated by potentiometric and spectrophotometric techniques. The kinetics of base hydrolysis of the above esters in the presence of copper(II)-glycyl-L-tyrosine complex was studied at 30°C.     

Time delay matrix at the spectrum edge and the minimal chaotic cavities

Self-interstitial interactions causing volume expansion in bcc Fe are studied through an idealized microstructure evolution model in which only self-interstial atoms (SIAs) are inserted. Using a combination of non-equilibrium molecular dynamics simulations and a metadynamics algorithm, meta-stable SIA clusters are observed to nucleate and grow into dislocation loops or localized amorphous phases, both contributing to swelling behavior persisting well beyond the atomistic time scale. A non-monotonic local density variation with dose rate is found and attributed to competing evolutions of different defective structures.