Ligand‐based design,virtual screening,and ADME/T‐based profiling on a dataset of 1,3,5‐triazine‐substituted benzene sulfonamides as carbonic anhydrase inhibitors

A quantitative structure–activity relationship (QSAR) analysis was performed on a dataset of 62 (1,3,5‐triazine‐substituted) benzene sulfonamides as carbonic anhydrase II and IX inhibitors using simulated annealing‐based multiple linear regression analysis. The selected QSAR model for carbonic anhydrase II inhibition (cross‐validated Q² = 0.689, , ) showed that aromaticity, lipophilicity, electronegativity, and molecular projection in the XZ plane influence the activity, whereas that for carbonic anhydrase IX inhibition (cross‐validated Q² = 0.767, , ) showed that activity was influenced by hydrophilicity, linker between the aromatic rings, electronegativity, and molecular weight. The QSAR model selected was internally and externally validated to define its predictability. Activity prediction of an external dataset containing nine compounds (within the same sphere of applicability) was performed to prove the models' specificity, selectivity, and sensitivity. The hypothesis in the form of the QSAR model was used for ligand‐based virtual screening on the ZINC database to obtain some potential hits. Similarly, docking studies on screened hits showed that the molecules interact and orient at the catalytic site in a way similar to acetazolamide. Additionally, an absorption, distribution, metabolism, excretion, and toxicity screening was also performed, and results showed that most of the compounds that can be possible drug candidates obey the Lipinski rule of five and Jorgensen rule of three. Copyright © 2013 John Wiley & Sons, Ltd.     

Sulfated Galactans of Champia indica and Champia parvula (Rhodymeniales,Rhodophyta) of Indian Waters

Sulfated galactans of the red seaweed species Champia indica and Champia parvula of Indian waters were extracted and purified by ion exchange chromatography. These were characterized by infrared and ¹³C NMR spectroscopy as well as by GC-MS analysis of alditol acetate derivatives produced by reductive hydrolysis/acetylation of sulfated and desulfated and their methylated samples. The sulfated galactans of these Champia species contained alternating β-(1→3)-linked galactopyranosyl units with sulfation at the 2-position and α-(1→4)-linked galactopyranosyl units having sulfation at both the 2- and 3-positions. Other minor substitutions included 6-O-methyl ether of the β-(1→3)-linked galactose residues only in Champia parvula.     

Diastereoselective one-pot Wittig olefination-Michael addition and olefin cross metathesis strategy for total synthesis of cytotoxic natural product (+)-varitriol and its higher analogues

A stereoselective route for the total synthesis of anticancer marine natural product (+)-varitriol (1) is detailed herein. The impressive biological activity and interesting structural features of natural (+)-varitriol fuelled us to undertake the synthesis of some higher analogues (1a-j) of this molecule. The key features of the synthetic strategy include one-pot Wittig olefination followed by a highly diastereoselective oxa-Michael addition to assemble stereochemically pure tetrasubstituted THF moiety of the natural varitriol and olefin cross metathesis to couple the aromatic part with tetrasubstituted THF moiety. The total synthesis of title natural product is efficient with 21.8% overall yield for 9 linear steps from D-ribose and thus facilitates the more scaled-up practical route for the synthesis of 1 and its analogues as well. The synthetic (+)-varitriol (1) and its analogues were screened for their cytotoxicity. The present synthetic approach paves the way for preparation of numerous analogues of the title natural product for drug development.     

Analytical expression of the steady-state catalytic current of mediated bioelectrocatalysis and the application of He’s Homotopy perturbation method

A mathematical model of mediated bioelectrocatalysis is restudied in this paper. Here He’s Homotopy perturbation method is implemented to give approximate and analytical solutions of steady-state non-linear reaction diffusion equation containing a non-linear term related to Michaelis–Menten kinetics of the enzymatic reaction. Approximate analytical expressions for mediator concentration and current have been derived for all values of saturation parameter α and reaction diffusion parameter k for the various types of boundary conditions. The Homotopy perturbation method which produces the solutions in terms of convergent series, requiring no linearization or small perturbation. These analytical results are compared with numerical results (Matlab program) and are found to be in good agreement.     

Animal models of acute photodamage: comparisons of anatomic, cellular and molecular responses in C57BL/6J, SKH1 and Balb/c mice

Human cutaneous photodamage is a major medical problem that includes premature aging and fragility of the skin. Nonxenografted animal models have not been comparatively evaluated for how well they resemble the changes seen in human skin. Here, we sought to identify a suitable mouse model that recapitulates key anatomic, cellular and molecular responses observed in human skin during acute UV exposure. Adult females from three strains of mice, C57BL/6J, SKH1 and Balb/c were exposed to UVB and then evaluated 3 or 20 h after the last irradiation. Skin from UVB-exposed C57BL/6J mice showed features resembling human photodamage, including epidermal thickening, infiltration of the dermis with inflammatory cells, induction of tumor necrosis factor-α (TNF-α) mRNA, accumulation of glycosaminoglycans, particularly hyaluronan in the epidermis and loss of collagen. Hairless SKH1 mouse skin responded similarly, but without any induction of TNF-α mRNA or chondroitin sulfate. Irradiated Balb/c mice were the least similar to humans. Our results in C57BL/6J mice and to a lesser extent in SKH1 mice, show cutaneous responses to a course of UVB-irradiation that mirror those seen in human skin. Proper choice of model is critical for investigating cellular and molecular mechanisms of photodamage and photoaging.     

Primitive polynomials,singer cycles and word-oriented linear feedback shift registers

Using the structure of Singer cycles in general linear groups, we prove that a conjecture of Zeng et al. (Word-Oriented Feedback Shift Register: σ-LFSR, 2007) holds in the affirmative in a special case, and outline a plausible approach to prove it in the general case. This conjecture is about the number of primitive σ-LFSRs of a given order over a finite field, and it generalizes a known formula for the number of primitive LFSRs, which, in turn, is the number of primitive polynomials of a given degree over a finite field. Moreover, this conjecture is intimately related to an open question of Niederreiter (Finite Fields Appl 1:3–30, 1995) on the enumeration of splitting subspaces of a given dimension.     

Chemically modified oximato complexes of titanium(IV) isopropoxide as new precursors for the sol-gel preparation of nano-sized titania: Crystal and molecular structure of [Ti{ONC10H16}4·2CH2Cl2]

Reactions of [Ti(OPrⁱ)₄] with various oximes, in anhydrous refluxing benzene yielded complexes of the type [Ti{OPrⁱ}_4−n{L}_n], where, n = 1-4 and LH = (CH₃)₂CNOH (1-4), C₉H₁₆CNOH (5-8) and C₉H₁₈CNOH (9-12). The compounds were characterized by elemental analyses, molecular weight measurements, FAB-mass, FT-IR and NMR (¹H, ¹³C{¹H}) spectral studies. The FAB-mass spectra of mono- (1), and di- (2), (6), (10) substituted products indicate their dimeric nature and that of tri- (3) and tetra- (4), (8) substituted derivatives suggest their monomeric nature. Crystal and molecular structure of [Ti{ONC₁₀H₁₆}₄·2CH₂Cl₂] (8A) suggests that the oximato ligands bind the metal in a dihapto η²-(N, O) manner, leading to the formation of an eight coordinated species. Thermogravimetric curves of (3), (6) and (10) exhibit multi-step decomposition with the formation of TiO₂ as the final product in each case, at 900 °C. Low temperature (∼600 °C) sol-gel transformations of (2), (3), (4), (6), (7) and (8) yielded nano-sized titania (a), (b), (c), (d), (e) and (f), respectively. Formation of anatase phase in all the titania samples was confirmed by powder XRD patterns, FT-IR and Raman spectroscopy. SEM images of (a), (b), (c), (d), (e) and (f) exhibit formation of nano-grains with agglomer like surface morphologies. Compositions of all the titania samples were investigated by EDX analyses. The absorption spectra of the two representative samples, (a) and (f) indicate an energy band gap of 3.17 eV and 3.75 eV, respectively.     

Group Algebras Satisfying a Certain Lie Identity

ABSTRACT

Let K be a field of characteristic p ≠ 2 and let G be any group. A characterization of group algebras KG satisfying the Lie identity [[x,y],[u,v],[z,t]] = 0 for all x,y,u,v,z,t ? KG is obtained.