Methoxy-activated indole-7-carbohydrazides; synthesis,antioxidant, and anticancer properties

Indole has been known as a key heterocyclic motif in the development of new structures for both chemical and biological properties. In this current study, a new range of indole-7-carbohydrazides has been successfully synthesized starting from the readily available 3-phenyl and 2,3-diphenyl 4,6-dimethoxyindoles. The structures of the novel compounds were confirmed by utilizing ¹H NMR, ¹³C NMR, FT-IR, high-resolution mass spectrometry, and single crystal X- ray diffraction techniques. In addition, the indole-7-carbohydrazides showed promising antioxidant results in preliminary screens. Some of the new compounds generated from dimethoxy indoles were also screened for their anticancer activity against SH-SHY5Y (human neuroblastoma), AGS (human gastric adenocarcinoma), and MDA-MB-231 (human breast adenocarcinoma) cell lines. The results revealed that the compound 12 was the promising candidate, showing cytotoxic effects on both neuroblastoma, stomach, and breast cancer cells.     

Synthesis,cytotoxic, and carbonic anhydrase inhibitory effects of new 2-(3-(4-methoxyphenyl)-5-(aryl)-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazole derivatives

2-(3-[4-Methoxyphenyl]-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazoles ( 1b-7b ) were synthesized for the first time except 1b , and spectral methods such as ¹H NMR, ¹³C NMR and HRMS were utilized to illuminate the chemical structures of the synthesized compounds. Phenyl ( 1b ), 2-methoxyphenyl ( 2b ), 4-methoxyphenyl ( 3b ), 4-methoxy-3-hydroxyphenyl ( 4b ), 2,5-dimethoxyphenyl ( 5b ), 3,4,5-trimethoxyphenyl ( 6b ), or thiophene-2-yl ( 7b ) was used as a aryl part. The inhibitory effects of the compounds were evaluated toward human carbonic anhydrase I and II enzymes (hCA I and hCA II). In vitro cytotoxic effects of the compounds against human oral squamous carcinomas and human normal oral cells were carried out via MTT. The compounds ( 1b-7b ) had Ki values of 36.87 ± 11.62-66.24 ± 2.99 μM (hCA I) and 22.66 ± 1.41-89.95 ± 6.25 μM (hCA II). Compounds 1b (Ki = 36.87 ± 11.62 μM) toward hCA I, 6b (Ki = 22.66 ± 1.41 μM) toward hCA II had significant enzyme inhibitory potency. Compound 6b had the highest tumor selectivity (TS = 29.3) and potency selectivity expression (PSE = 272.3) values. Therefore, compounds 1b and 6b with CAs inhibition effect and compound 6b with the cytotoxicity may be forwarded to further studies as potent compounds.     

Variational calculations on the energy levels of graphene quantum antidots

The critical properties of the two-dimensional Ising and Blume-Capel model on directedsmall-world lattices with quenched connectivity disorder are investigated. The disordered system is simulated by applying the Monte Carlo method with heat bath update algorithm and histogram re-weighting techniques. The critical temperature, as well as the critical exponents are obtained. For both models the critical parameters have been obtained for several values of the rewiring probability p. It is found that these disorder systems do not belong to the same universality class as two-dimensional ferromagnetic model on regular lattices. In particular, the Blume-Capel model, with zero crystal field interaction, on a directedsmall-world lattice presents a second-order phase transition for p < p _c , and a first-order phase transition for p > p _c , where p _c  ≈ 0.25. The critical exponents for p < p _c are different from those of the same model on a regular lattice, but are identical to the exponents of the Ising model on directedsmall-world lattice.     

Bromination of 4,6-dimethoxyindoles

The bromination of activated 4,6-dimethoxyindoles can be carried out effectively provided that an electron-withdrawing group is also present. Thus the range of products includes 2-bromo-7-formyl or 2-bromo-7-acetylindoles 13a–c and 16, 7-bromo-2-acetylindole 21, 2,5-dibromo-7-acetylindole 17, 2,5-dibromo-N-sulfonylindole 27, and 2,7-dibromo-N-acetylindole 24. Acetyl and sulfonyl protecting groups on nitrogen can be removed to give 2-bromoindoles 28a–b, 2,5-dibromoindole 29, and 2,7-dibromoindole 4.     

Polaronic effects in one-dimensional quantum antidot arrays

We study the effect of polaronic corrections arising from theelectron-longitudinal optical phonon interaction on the energyspectrum of a two-dimensional electron system with a one-dimensionalperiodic antidot array geometry created by a weak electrostaticmodulation potential, and subjected to a weak magnetic fieldmodulation as well as a uniform strong perpendicular staticmagnetic field. To incorporate the effects of electron-phononinteractions within the framework of Fröhlich polaron theory, wefirst apply a displaced-oscillator type unitary transformation todiagonalise the relevant Fröhlich Hamiltonian, and we thendetermine the parameters of this transformation together with theparameter included in the electronic trial wave function . On thebasis of this technique, it has been shown that the polaroniccorrections have non-negligible effects on the electronic spectrumof a two-dimensional electron system with a quantum antidot array,since switching such an interaction results in shifting thedegeneracy restoring points of Landau levels wherein the flatbandcondition is fulfilled, thus suppressing the Weiss oscillations.     

Distribution of eigenvalues for the discontinuous boundary-value problem with functional-manypoint conditions

In this study, we investigate the boundary-value problem with eigenvalue parameter generated by the differential equation with discontinuous coefficients and boundary conditions which contains not only endpoints of the considered interval, but also a point of discontinuity, a finite number of internal points and abstract linear functionals. So our problem is not a pure boundary-value one. We single out a class of linear functionals and find simple algebraic conditions on the coefficients which guarantee the existence of an infinite number of eigenvalues. Also, the asymptotic formulas for the eigenvalues are found. The results obtained in this paper are new, even in the case of boundary conditions either without internal points or without linear functionals.     

The ground- and first-excited states of magnetopolarons in two-dimensional quantum dots for all coupling strengths

The ground- and first-excited state energies of a magnetopolaron in a two dimensional parabolic quantum dot are studied within a variational calculation for all coupling strength. The Lee-Low-Pines-Huybrecht variational technique that is developed previously for all coupling strength has been extented for polarons in a magnetic field. The dependence of the polaronic correction on the magnetic field and the confinement length is investigated. The polarization potential and the renormalized cyclotron masses as a function of electron-phonon coupling strength and the strength of both confinement potential and magnetic field are also studied within the same approach. Received 16 December 2002 / Received in final form 14 April 2003 Published online 4 June 2003 RID="a" ID="a"e-mail: kandemir@science.ankara.edu.tr     

Human Serum Albumin−Gold Nanoparticle Based Impedimetric Sensor for Sensitive Detection of miRNA-200c

Here, human serum albumin conjugated gold nanoparticles (HSA−AuNPs) were synthesized by a simple route to develop an impedimetric sensor for miRNA-200c detection based on a selective oligo-hybridization process without any labeling. The synthetic DNA capture probe for miRNA-200c was decorated onto the HSA−AuNPs modified pencil graphite electrodes. Impedimetric signals were monitored after the hybridization process between the DNA probe and target miRNA-200c. HSA−AuNPs adsorption time, incubation time of the capture probe and hybridization time-temperature were optimized. The proposed miRNA-200c biosensor demonstrated proper sensitivity and selectivity, low detection limit (1.13 fM), good reproducibility and simple direct detection of miRNA-200c in serum.     

Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity

In this study, we aimed to design and synthesize novel molecules carrying both the thiazole and piperazine rings in their structures and to investigate their antinociceptive activity. Targeted compounds were obtained by reacting thiosemicarbazide derivative and appropriate 2-bromoacetophenone in ethanol. The structures of the obtained compounds were determined using data from various spectroscopic methods (IR, ¹H-NMR, ¹³C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds 3a–3c, 3f, and 3g (50 mg/kg) significantly prolonged reaction times of animals in tail-clip and hot-plate tests compared to the controls, indicating that these compounds possess centrally mediated antinociceptive activities. Furthermore, these compounds reduced the number of writhing behaviors in the acetic acid-induced writhing tests, showing that the compounds also possess peripheral antinociceptive activity. In the mechanistic studies, naloxone pre-treatments abolished the antinociceptive activities of compounds 3a–3c, 3f, and 3g, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-opioid receptor proteins supported the pharmacological findings. This study is the first showing that molecules designed to bear thiazole and piperazine moieties together on their structure exert centrally and peripherally mediated antinociceptive effects by activating the opioid system.