The design of TOPK inhibitors using structure-based pharmacophore modeling and molecular docking based on an MD-refined homology model

Molecular Diversity - The TOPK enzyme (also known as PBK) is a serine-threonine protein kinase that is rarely detected in normal tissues yet is found to be overexpressed and activated in a variety...     

Periodic Golay pairs and pairwise balanced designs

Journal of Algebraic Combinatorics - In this paper we exploit a relationship between certain pairwise balanced designs with v points and periodic Golay pairs of length v, to classify periodic Golay...     

Reversible C=C Bond Activation by an Intramolecularly Coordinated Antimony(I) Compound

The reaction of N,C,N-chelated stibinidene ArSb ( 1 ) (Ar=C₆H₃-2,6-(CH=NtBu)₂) with selected N-alkyl/aryl-maleimides RN(C(O)CH)₂ (R=Me, tBu, Ph) gave the addition products with bridged bicyclic [2.2.1] structure containing an antimony atom at the bridgehead position, fused with a 6-membered benzene and a 5-membered N-alkyl/aryl-pyrrolidine ring. These compounds were completely characterized. More importantly, additional studies showed that these reactions are reversible in solution, thereby representing an unprecedented reversible activation of a C=C bond by an antimony(I) compound.     

Electrically Switchable Magnetic Molecules: Inducing a Magnetic Coupling by Means of an External Electric Field in a Mixed‐Valence Polyoxovanadate Cluster

Herein we evaluate the influence of an electric field on the coupling of two delocalized electrons in the mixed‐valence polyoxometalate (POM) [GeV₁₄O₄₀]^8? (in short V₁₄) by using both a t‐J model Hamiltonian and DFT calculations. In absence of an electric field the compound is paramagnetic, because the two electrons are localized on different parts of the POM. When an electric field is applied, an abrupt change of the magnetic coupling between the two delocalized electrons can be induced. Indeed, the field forces the two electrons to localize on nearest‐neighbors metal centers, leading to a very strong antiferromagnetic coupling. Both theoretical approaches have led to similar results, emphasizing that the sharp spin transition induced by the electric field in the V₁₄ system is a robust phenomenon, intramolecular in nature, and barely influenced by small changes on the external structure.     

Reactivity of a N-Coordinated Germylene-Borane Complex: From Ge→B to Ge→Ga Coordination

Reactivity studies of the Ge^II→B complex L(Cl)Ge⋅BH₃ ( 1 ; L=2-Et₂NCH₂-4,6-tBu₂-C₆H₂) were performed to determine the effect on the Ge^II→B donation. N-coordinated compounds L(OtBu)Ge⋅BH₃ ( 2 ) and [LGe⋅BH₃]₂ ( 3 ) were prepared. The possible tuning of the Ge^II→B interaction was proved experimentally, yielding compounds 1-PPh₂-8-(LGe)-C₁₀H₆ ( 4 ) and L(Cl)Ge⋅GaCl₃ ( 5 ) without a Ge^II→B interaction. In 5 , an unprecedented Ge^II→Ga coordination was revealed. The experimental results were complemented by a theoretical study focusing on the bonding in 1 − 5 . The different strength of the Ge^II→E (E=B, Ga) donation was evaluated by using energy decomposition analysis. The basicity of different L(X)Ge groups through proton affinity is also assessed.     

Spectral analysis of Pk Finite Element matrices in the case of Friedrichs–Keller triangulations via Generalized Locally Toeplitz technology

In the present article, we consider a class of elliptic partial differential equations with Dirichlet boundary conditions and where the operator is div(?a( x )?·), with a continuous and positive over $\stackrel{￣}{\mathrm{\Omega }}$, Ω being an open and bounded subset of ${\mathbb{R}}^d$, d≥1. For the numerical approximation, we consider the classical ${\mathbb{P}}_k$ Finite Elements, in the case of Friedrichs–Keller triangulations, leading, as usual, to sequences of matrices of increasing size. The new results concern the spectral analysis of the resulting matrix‐sequences in the direction of the global distribution in the Weyl sense, with a concise overview on localization, clustering, extremal eigenvalues, and asymptotic conditioning. We study in detail the case of constant coefficients on Ω=(0,1)² and we give a brief account in the more involved case of variable coefficients and more general domains. Tools are drawn from the Toeplitz technology and from the rather new theory of Generalized Locally Toeplitz sequences. Numerical results are shown for a practical evidence of the theoretical findings.     

Synthesis,Characterization and Evaluation of the Antibacterial and Antitumor Activity of HalogenatedSalen Copper (II) Complexes derived from Camphoric Acid

Platinum metal complexes are the most common chemotherapeutics currently used in cancer treatment. However, the frequent adverse effects, as well as acquired resistance by tumor cells, urge the development of effective alternatives. In the recent past, copper complexes with Schiff base ligands have emerged as good alternatives, showing interesting results. Accordingly, and in continuation of previous studies in this area, three new camphoric acid-derived halogenated salen ligands and their corresponding Cu (II) complexes were synthesized and their antitumor activity was evaluated in order to determine the influence of the type and number of halogens present (Br, Cl). The in vitro cytotoxic activity was screened against colorectal WiDr and LS1034 and against breast MCF-7 and HCC1806 cancer cell lines. The results proved the halogenated complexes to be very efficient, the tetrachlorinated Cu (II) complex being the most promising, presenting IC₅₀ of 0.63–1.09 μM for the cell lines studied. The complex also shows selectivity to colorectal cancer cells compared to non-tumor colon cells. It is worth highlighting that the tetrachlorinated Cu (II) complex, our most efficient complex, shows a significantly more powerful antitumor effect than the reference drugs currently used in conventional chemotherapy. The halogenated salen and corresponding complexes were also screened for their antimicrobial activity against four bacterial species-Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa-and four fungal species-Candida albicans, Candida glabrata, Aspergillus fumigatus and Alternaria alternata. The compounds were found to exhibit moderate to strong antibacterial activity against the bacterial strains studied. NMR studies and theoretical calculations provided some insight into the structure of the ligands and copper complexes. Considering the results presented herein, our work validates the potential use of copper-based chemotherapeutics as alternatives for cancer treatment.