Synthesis and biological evaluation in vitro and in silico of N-propionyl-N′-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi

Molecular Diversity - An N-acylhydrazone scaffold has been used to develop new drugs with diverse biological activities, including trypanocidal activity against different strains of Trypanosoma...     

Design,synthesis, and in silico studies of novel eugenyloxy propanol azole derivatives having potent antinociceptive activity and evaluation of their β-adrenoceptor blocking property

The design, synthesis, antinociceptive and β-adrenoceptor blocking activities of several eugenyloxy propanol azole derivatives have been described. In this synthesis, the reaction of eugenol with epichlorohydrin provided adducts 3 and 4 which were N-alkylated by diverse azoles to obtain the eugenyloxy propanol azole analogues in good yields. Adducts 3 and 4 were also reacted with azide ion to obtain the corresponding azide 6. The ‘Click’ Huisgen cycloaddition reaction of 6 with diverse alkynes afforded the title compounds in good yields. The synthesized eugenyloxy propanol azole derivatives were in vivo studied for the acute antinociception on male Spargue Dawley rats using tail-flick test. Compounds 5f, 5g, 7b and 11a exhibited potent analgesic properties in comparison with eugenol as a standard drug. In addition, all compounds were ex vivo tested for β-adrenoceptor blocking properties on isolated left atrium of male rats which exhibited partial antagonist or agonist behaviour compared to the standard drugs. The molecular docking study on the binding site of transient receptor potential vanilloid subtype 1 (TRPV1) has indicated that like capsaicin, eugenyloxy propanol azole analogues exhibited the strong affinity to bind at site of TPRV1 in a “tail-up, head-down” conformation and the presence of triazolyl moieties has played undeniable role in durable binding of these ligands to TRPV1. The in silico pharmacokinetic profile, drug likeness and toxicity predictions carried out for all compounds determined that 5g can be considered as potential antinociceptive drug candidate for future research.

     

Antibacterial evaluation and molecular docking studies of pyrazole–thiosemicarbazones and their pyrazole–thiazolidinone conjugates

Molecular Diversity - A library of pyrazole–thiazolidinone conjugates was synthesized using a molecular hybridization approach through a Vilsmeier–Haack reaction. The compounds were...     

Synthesis of 1,2,3,triazole modified analogues of hydrochlorothiazide via click chemistry approach and in-vitro α-glucosidase enzyme inhibition studies

Molecular Diversity - The current study was aimed to discover potent inhibitors of α-glucosidase enzyme. A 25 membered library of new 1,2,3-triazole derivatives of hydrochlorothiazide (1)...     

Structure elaboration of isoniazid: synthesis,in silico molecular docking and antimycobacterial activity of isoniazid–pyrimidine conjugates

Molecular Diversity - Designing small molecule-based new drug candidates through structure modulation of the existing drugs has drawn considerable attention in view of inevitable emergence of...     

Design,synthesis, molecular docking and in vitro evaluation of benzothiazole derivatives as 11β-hydroxysteroid dehydrogenase type 1 inhibitors

Molecular Diversity - 11-Beta hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates cortisol levels mainly in adipose, hepatic and brain tissues. There is a relationship between the high...     

Synthesis,vibrational and UV–visible studies of sodium cadmium orthophosphate

In this paper, NaCdPO₄ orthophosphate was prepared by solid-state reaction technique at high temperature. Structural, vibrational and optical properties have been investigated. X-ray powder diffraction analysis revealed that the titled compound crystallizes in the orthorhombic system with Pmnb space group. Vibrational study by means of Raman and FTIR spectroscopies confirms the existence of the (PO₄)^3? functional group. Optical properties were recorded at room temperature using UV–visible spectroscopy in the spectral range (200–800) nm. The UV–Vis absorption bands are attributed to the charge transfer from the oxygen ligands to the central phosphate atom inside the PO₄ ^3? groups. The optical absorbance was measured also to determinate the optical band gap using Kubelka–Munk function. The dispersion parameters (E₀ and E_d) of this compound were estimated using the Wemple Di-Domenico model.     

Synthesis,characterization and phase transition studies in 4-hexyloxy benzylidene 4’-alkoxyanilines

Synthesis and the characterization through polarizing optical microscope (POM) textures in number of 4-hexyloxy benzylidene 4’-alkoxyanilines, 6O.Om with m = 4, 6 to 10 liquid crystalline materials are carried out. Furthermore, the density and thermal expansion coefficient results reveal that the phase transitions present, viz., isotropic–nematic, nematic–SmC and SmC–SmI show first-order nature as expected. The transition temperatures obtained thorough the differential scanning calorimetry is found to be in agreement with the literature data. The first two compounds exhibit only the nematic phase while the next four compounds show enantiotropic SmC phase as per the literature data. The compound with m = 10 exhibits monotropic SmI phase. However, we, the authors, are able to observe this phase in addition to SmC and nematic through POM only as per the literature. The parameters calculated across the phase transitions and in the phases are in agreement with the body of the data available.     

The evaluation map in field theory,sigma-models and strings—II

In this paper, we examine specifically the rôle of the evaluation map in sigma-models and strings. We discuss the difference between sigma-models and field theory, as far as anomaly cancellation is concerned. The introduction of the Wess—Zumino terms in different sigma-models is considered. Anomalies in string theory are discussed, with special attention to the conformal anomalies and to the sigma-model anomalies for the imbedded (or immersed) world-sheet of the string. Conformal anomalies in two dimensions are connected to holomorphic and gravitational anomalies. In order to have the cancellation of the sigma-model anomalies of the string, certain topological conditions must be satisfied by the ambient manifold. The rôle of the evaluation map in the calculations of global anomalies is also discussed, both for field theories and for sigma-models. In particular global anomalies are connected with the differential characters of Cheeger and Simons. We show that the absence of global anomalies in sigma-models is guaranteed by the absence of torsion in suitable homology groups of the target space.On leave of absence from Dipartimento di Fisica dell'Università di Padova and Instituto Nazionale di Fisica Nucleare, Sezione di PadovaWork supported in part by: Ministero Pubblica Istruzione (research project on Geometry and Physics)On leave of absence from Department of Mathematics, University of North Carolina, Chapel Hill, N.C. 27514. From August 1 until December 20 at the School of Mathematics, Institute for Advanced Study Princeton NJ 08540, USA. Work supported in part by N.S.F.     

Neutral and anionic duality of 1,2,4-triazole α-amino acid scaffold in 1D coordination polymers

A tiny supramolecular synthon, 4H-1,2,4-triazol-4-yl acetic acid (HGlytrz) which is bifunctional by design having an electronic asymmetry and conformational flexibility has been introduced to synthesize iron(II) complexes. Having 1,2,4-triazole or carboxylic extremities on the same framework HGlytrz could display dual functionality by acting as a neutral as well as anionic ligand based on the possibility of deprotonation of carboxylic group. Four new iron(II) HGlytrz complexes with ClO $_{4}^{-}$ (1), NO $_{3}^{-}$ (2), BF $_{4}^{-}$ (3) and CF₃SO $_{3}^{-}$ (4) anions were prepared. Formulation of their composition which is complicated due to ligand deprotonation is discussed. Unlike its ester protected counterpart ethyl-4H-1,2,4-triazol-4-yl-acetate (αGlytrz) which show hysteretic room temperature spin crossover, 1–4 remain in the high-spin state as revealed by ⁵⁷M?ssbauer spectroscopy. Prospects of such 1D coordination polymers with dangling unbounded carboxylic entities in the realm of self-assembled monolayer (SAM) are discussed.     

Synthesis,anti-proliferative activity,theoretical and 1H NMR experimental studies of Morita–Baylis–Hillman adducts from isatin derivatives

Molecular Diversity - Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a...     

The chemistry of aminoguanidine derivatives – preparation,crystal structure,thermal properties,and molecular docking studies of aminoguanidinium salts of several carboxylic acids

The reaction of aminoguanidine bicarbonate (Amg) with oxamic, oxalic, malonic and sulfoacetic acids yielded (AmgH)H₂NOC–COO (1), OOC–CONHNHC(NH₂)NH₂ (2) (AmgH)HOOC–CH₂–COO (3) and O₃S–CH₂–CONHNHC(NH₂)NH₂ (4), respectively. For the first time, we studied the salt-forming ability of aminoguanidine with several carboxylic acids, such as oxamic, oxalic, malonic and sulphoacetic acids. We also compared the structural and thermal properties of these salts. Oxamic and malonic acids form only mono-aminoguanidinium salts, whereas oxalic acid mainly forms di-aminoguanidinium oxalate. In addition, oxalic acid forms guanylhydrazido-oxalic acid which exists as zwitter ion. Unlike other acids, sulfoacetic acid readily forms only the zwitter ionic salts (2-guanylhydrazido-oxo-methanesulfonic acid) rather than the usual simple salt. This result may be a result of the highly acidic nature of the sulfonic group, which favors acid catalyzed condensation. More significantly, for the first time, the ability guanylhydrazido-oxalic acid (2) and 2-guanylhydrazido-oxo-methanesulfonic acid (4) to inhibit human butyrylcholinesterase (human BChE) receptor has been studied with a molecular docking approach. The binding of the compounds to human BChE was examined as it is crucial to understanding the biological significance of aminoguanidine derivatives. The compounds were identified and characterized by analytical, FT-IR spectroscopic and thermal studies. Furthermore, the structures of compounds 1, 2 and 4 were confirmed by single X-ray diffraction studies. Compounds 1 and 2 crystallized in a monoclinic crystal system with P2₁/c and Cc space groups, respectively, whereas compound 4 crystalized in an orthorhombic system with a Pbca space group. All the compounds (1–4) underwent endo- followed by exothermic decomposition in the temperature range from 130 to 600 °C to yield gaseous products.     

Synthesis,structural, electrical and magnetic studies of La0.5Ca0.45−xSrxBa0.05MnO3

Half doped mixed valence manganite system La_0.5Ca_0.45?xSr_xBa_0.05MnO₃ (with x=0.1, 0.2, and 0.3) synthesized through a low temperature nitrate route is systematically investigated in this paper. The electronic transport and magnetic properties are analyzed and compared apart from the study of unit cell structure and composition. The system is found to crystallize only in orthorhombic structure (Pnma) and the electronic phase transitions are observed to be of second order. The charge and orbital ordering have been observed to coexist with ferromagnetism in x=0.1 compound. Application of small polaron and variable range hopping models to resistivity data of the system corresponding to high temperature range shows increasing mobility of e_g electrons with x, with the later model describing the electronic transport very closely than the former. The temperature dependent magnetization of the compounds shows monotonic increase of paramagnetic to ferromagnetic transition (T_C) with x. Ferromagnetism is exhibited for the complete temperature range down from respective T_C in contrast to antiferromagnetism usually exhibited by half-doped compounds in the low temperature range. The plots of magnetization versus magnetic field reveal a transition from soft to hard magnetic character for all the compounds as the temperature is lowered.     

Morita–Baylis–Hillman adducts derived from thymol: synthesis,in silico studies and biological activity against Giardia lamblia

Molecular Diversity - Giardiasis is a neglected disease, and there is a need for new molecules with less side effects and better activity against resistant strains. This work describes the...     

Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: in vitro and in vivo biological activities against Alzheimer’s disease

Molecular Diversity - Alzheimer’s disease (AD) is now ranked as the third leading cause of death after heart disease and cancer. There is no definite cure for AD due to the multi-factorial...     

Far infrared studies of lattice and free carrier effects in CdxHg1−xSe

Far infrared reflection spectra of Cd_xHg_1−xSe are measured in the region 20 to 600 cm^-1 at temperature between 5 and 77 K. Reflection spectra are explained well by the dynamic dielectric function which is constructed as a sum of interband, intraband and phonon contributions. The plasma-LO phonon coupling and free carrier effects are discussed.     

New Pd(II)–mechlorethamine complex: Synthesis,NMR study of hydrolytic activity and in vitro evaluation of antiradical property of new complex and its alkylating precursor

The reaction of PdCl₂ with anticancer-alkylating agent mechlorethamine hydrochloride (CH₃NH(C₂H₄Cl)₂ = HN2 x HCl), in the molar ratio 1:2, affords the complex [CH₃NH(C₂H₄Cl)₂]₂[PdCl₄] ([H2N2]₂[PdCl₄]). Novel Pd(II) complex and the complex precursor mechlorethamine hydrochloride were tested for their antiradical property. Both present weak interaction with 2, 29-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS). Assays with soybean lipoxygenase and with superoxide anion radicals in vitro showed very high radical scavenging activity of the complex, whereas the complex precursor mechlorethamine hydrochloride presents lower inhibition. Hydrolytic activity of new complex with N-acetylhistidylglycine (AcHis–Gly) was also studied. It was established that regioselective cleavage of the amide bond of the investigated dipeptide had occurred after heating at 60 °C and at pH = 1.5 for 36 h.     

First-principles studies of the structural,electronic and optical properties of Zn1−xCdxS and ZnS1−ySey alloys

Using the density functional theory calculations, we studied the structural, electronic and optical properties of zincblende Zn_1?xCd_xS and ZnS_1?ySe_y alloys. Calculated structures and band gaps of these alloys are in good agreement with available experimental and other theoretical values. Present results show that the prominent peaks of the dielectric functions and absorption coefficients have a slight red shift and the amplitudes become larger with the increasing concentration of Cd and Se. Moreover, present findings predict that Zn_1?xCd_xS and ZnS_1?ySe_y alloys are promising for solar cells and photoconductor and electroluminescent devices due to their high absorption of solar radiations and photoconductivity in the energy region from visible light to ultraviolet.     

Fundamental studies and device application of δ-doping in GaAs Layers and in AlxGa1−xAs/GaAs heterostructures

In addition to the realization of atomically abrupt interfaces in III–V semiconductors by molecular beam epitaxy, the confinement of donor and acceptor impurities to an atomic plane normal to the crystal growth direction, called-doping, is important for the fabrication of artifically layered semiconductor structures. The implementation of-function-like doping profiles by using Si donors and Be acceptors generates V-shaped potential wells in GaAs and Al_xGa_1–xAs with a quasi-two-dimensional (2D) electron (or hole) gas. In this review we define three areas of fundamental and device aspects associated with-doping. (i) The prototype structure of-doping formed by a single atomic plane of Si donors in GaAs allows to study the 2D electron gas by magnetotransport and tunneling experiments, to study the metal-insulator transition, and to study central-cell and multivalley effects. In addition, non-alloyed ohmic contacts to GaAs and GaAs field-effect transistors (-FETs) with a buried 2D channel of high carrier density can be fabricated from-doped material. (ii) GaAs sawtooth doping superlattices, consisting of a periodic sequence of alternating n- and p-type-doping layers equally spaced by undoped regions, emit light of high intensity at wavelengths of 0.9 < <1.2 [m], which is attractive for application in photonic devices. The observed carrier transport normal to the layers due to tunneling indicates the feasibility of this superlattice as effective-mass filter. (iii) The confinement of donors (or acceptors) to an atomic (001) plane in selectively doped Al_xGa_1–xAs/GaAs heterostructures leads to very high mobilities, to high 2D carrier densities, and to a reduction of the undesired persistent photo-conductivity. These-doped heterostructures are thus important for application in transistors with improved current driving capabilities.Extended version of a paper presented at the18th Int. Symp. GaAs Related Compounds (Heraklion, Crete, 1987)     

Adsorption of water—methanol mixtures in carbon and aluminosilicate pores: a molecular simulation study

A theoretical study is reported of the adsorption behaviour of water—methanol mixtures in slit carbon and in uncharged alumino-silicate micropores. The adsorption isotherms are obtained for a pore of width of 2 nm and at a temperature of 298 K from grand canonical ensemble Monte Carlo simulations. The results show that the graphite and uncharged silicate surfaces are covered by a dense layer of flatly adsorbed water and methanol molecules having weaker hydrogen bonding. In the interior of the pore, the fluid exhibits bulk-like behaviour with a stronger hydrogen bonded structure. Solvation forces are also calculated as a function of pore size. The positive values found for the solvation force for all pore sizes reflect the hydrophobic interactions of the mixture with the carbon and uncharged alumino-silicate walls.