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•Cancer is the second major cause of mortality worldwide despite current chemotherapy.•Targeting aerobic glycolysis has become a research focus for developing anticancer drugs.•These ...antiglycolytic agents might also sensitize tumor cells to other cytotoxic therapies.•Although preclinical studies are promising, antiglycolytic therapy has not yet been translated into clinical practice.•This review presents the current state of glycolytic cancer therapy discussing the challenges and opportunitie.
Most solid tumor cells adapt to their heterogeneous microenvironment by depending largely on aerobic glycolysis for energy production, a phenomenon called the Warburg effect, which is a hallmark of cancer. The altered energy metabolism not only provides cancer cell with ATP for cellular energy, but also generate essential metabolic intermediates that play a pivotal role in the biosynthesis of macromolecules, to support cell proliferation, invasiveness, and chemoresistance. The cellular metabolic reprogramming in cancer is regulated by several oncogenic proteins and tumor suppressors such as hypoxia-inducible factor (HIF-1), Myc, p53, and PI3K/Akt/mTOR pathway. A better understanding of the mechanisms involved in the regulation of aerobic glycolysis can help in developing glycolytic inhibitors as anticancer agents. These metabolic antiglycolytic agents could be more effective if used in drug combinations to combat cancer. Several preclinical and early clinical studies have shown the effectiveness of targeting the glycolytic pathway as a therapeutic approach to suppress cancer progression. This review aimed to present the most recent data on the emerging drug candidate targeting enzymes and intermediates involved in glucose metabolism to provide therapeutic opportunities and challenges for antiglycolytic cancer therapy.
Recently, kisspeptin (KP) and gonadotropin inhibitory hormone (GnIH), two counteracting neuropeptides, have been acknowledged as significant regulators of reproductive function. KP stimulates ...reproduction while GnIH inhibits it. These two neuropeptides seem to be pivotal for the modulation of reproductive activity in response to internal and external cues. It is well-documented that the current metabolic status of the body is closely linked to its reproductive output. However, how reproductive function is regulated by the body's energy status is less clear. Recent studies have suggested an active participation of hypothalamic KP and GnIH in the modulation of reproductive function according to available metabolic cues. Expression of KISS1, the KP encoding gene, is decreased while expression of RFRP (NPVF), the gene encoding GnIH, is increased in metabolic deficiency conditions. The lower levels of KP, as suggested by a decrease in KISS1 gene mRNA expression, during metabolic deficiency can be corrected by administration of exogenous KP, which leads to an increase in reproductive hormone levels. Likewise, administration of RF9, a GnIH receptor antagonist, can reverse the inhibitory effect of fasting on testosterone in monkeys. Together, it is likely that the integrated function of both these hypothalamic neuropeptides works as a reproductive output regulator in response to a change in metabolic status. In this review, we have summarized literature from nonprimate and primate studies that demonstrate the involvement of KP and GnIH in the metabolic regulation of reproduction.
The title compound was synthesized and structurally characterized. Theoretical IR, NMR (with the GIAO technique), UV, and nonlinear optical properties (NLO) in four different solvents were calculated ...for the compound. The calculated HOMO–LUMO energies using time-dependent (TD) DFT revealed that charge transfer occurs within the molecule, and probable transitions in the four solvents were identified. The in silico absorption, distribution, metabolism, and excretion (ADME) analysis was performed in order to determine some physicochemical, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal properties of the molecule. Finally, molecular docking calculation was performed, and the results were evaluated in detail.
PVA/PVP films doped with zinc sulphate heptahydrate (ZnSO
4
·7H
2
O) nanoparticles (NPs) are prepared using an in situ chemical method. Furthermore, as-prepared samples are irradiated with an ...electron beam at doses of 20, 25, 30, 35, and 40 kGy. Elemental analyses using energy dispersive X-ray spectroscopy (EDXS) of the fresh films showed the existence of both zinc oxide and zinc sulphide as main and minor phases in sequence. Moreover, scanning electron microscope measurements (SEM) revealed that embedded Zn NPs have regular and evenly distributed pores inside PVA/PVP network. On the other hand, the structural variations due to e-beam irradiation are monitored by a high-resolution-transmission electron microscope (HR-TEM), which displayed that encapsulated Zn NPs are well dispersed and capped inside PVA/PVP structural network. The measured optical absorption coefficient (α) of PVA/PVP/zinc sulphate nanocomposite films showed an increase against e-beam dose. Moreover, the calculated optical energy gap, E
g
, exhibited a reduction from 3.31 to 2.82 eV against the increase in irradiation dose. Evaluated values of wavelength at zero material dispersion (WZMD) indicated that e-beam irradiation can tune the structure of the studied samples to be used as a data transmitter in optical fiber telecommunication in the IR spectral range of 1.6842–1.0351 μm.
•Syntheses of TlGaSSe single crystal for photo-device as a first time.•Scanning electron microscope (SEM) image shows that TlGaSSe has multilayers structure.•The external quantum efficiency value is ...found ∼193% at 10 μW cm−2 light intensity.•The values of detectivity are 4.41 × 1011 and 8.48 × 1010 Jones at 10 and 1000 μW cm−2.•TlGaSSe crystals is a good contender for visible light photodetector.
Herein, we present the results of high-performance visible light photodetector fabricated from the grown TlGaSSe single crystal for the first time. The growth direction was found to be (1 0 0) and layered structure was confirmed by scanning electron microscope (SEM) micrograph. The photocurrent observed to be increased with increasing the light intensity and voltage. The photo responsitivity (R), detectivity (D) and external quantum efficiency (EQE) were studied for the fabricated device. The maximum value of R is found to be ∼980 mA V−1. The D value shows a decrease with increasing the light intensity and found in a range of 4.41 × 1011 to 8.48 × 1010 Jones. Further, the maximum value of EQE was found ∼193% at a light intensity of 10 μW cm−2. Photoswitching behavior of the device was also studied and displayed that the ratio of on and off photo values ∼45:100. The values of growth and decay time were found to be ∼218 and 185 ms, respectively.
Reactions of 1-(5-methyl)-1H-1,2,3-triazol-4-yl)ethan-1-ones and benzaldehydes in ethanol under basic conditions gave the corresponding chalcones. Reactions of the chalcones combined with ...thiosemicarbazide in dry ethanol containing sodium hydroxide afforded the corresponding pyrazolin-N-thioamides. Reactions of the synthesized pyrazolin-N-thioamides and several ketones (namely, ethyl 2-chloro-3-oxobutanoate, 2-bromoacetylbenzofuran, and hydrazonoyl chloride) gave the corresponding novel 2-(1,2,3-triazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazoles in high yields (77–90%). Additionally, 2-(4,5-dihydro-1H-pyrazol-1-yl)-4-(1H-1,2,3-triazol-4-yl)thiazoles were obtained in high yields (84–87%) from reactions with N-pyrazoline-thioamides and 4-bromoacetyl-1,2,3-triazoles under basic conditions. The structures of six of the newly synthesized heterocycles were confirmed by X-ray crystallography.
P-glycoprotein (P-gp) imparts multi-drug resistance (MDR) on the cancers cell and malignant tumor clinical therapeutics. We report a class of newly designed and synthesized oxygen-heterocyclic-based ...pyran analogues (4a-l) bearing different aryl/hetaryl-substituted at the 1-postion were synthesized, aiming to impede the P-gp function. These compounds (4a-l) have been tested against cancerous PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines as well as non-cancerous HFL-1 and WI-38 cell lines to determine their anti-proliferative potency.The findings demonstrated the superior potency of 4a-c with 4-F, 2-Cl, and 3-Cl derivatives and 4h,g with 4-NO
, 4-MeO derivatives against PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines.Compounds 4a-c were tested for P-gp inhibition and demonstrated significant vigour against MCF-7/ADR cells with IC
= 5.0-10.7 μM. The Rho123 accumulation assay showed that compounds 4a-c adequately inhibited P-gp function, as predicted. Furthermore, 4a or 4b administration resulted in MCF-7/ADR cell accumulation in the S phase, while compound 4c induced apoptosis by causing cell cycle arrest at G2/M. The molecular docking was applied to understand the likely modes of action and guide us in the rational design of more potent analogs. The investigate derivatives showed their good binding potential for p-gp active site with excellent docking scores and interactions. Finally, the majority of investigated derivatives 4a-c derivatives showed high oral bioavailability, but they did not cross the blood-brain barrier. These results suggest that they have favorable pharmacokinetic properties. Therefore, these compounds could serve as leads for designing more potent and stable drugs in the future.
PVA/H2SO4/Ethanol doped with Silver nano-composite films are prepared using in-situ reduction method. The fresh samples are irradiated to Gamma rays with doses 0, 10, 20, 30, 40, and 50 kGy. The ...structural characterizations of as-prepared films are studied using XRD and UV absorbance techniques. The diffraction by X-ray revealed existence of Ag2O and Ag nano-particles, in the structural matrix of PVA, in the form of phase centered cubic structure. Furthermore, the fitted optical absorbance and measurements performed by HR-TEM illustrated that the embedded Ag nano-particles has a quasi-spherical shape with an average diameter ~25 nm. Furthermore, fitting the measured absorption coefficients revealed that the direct optical energy gap is the most probable transition. The wavelength at zero material dispersion showed an increase from 1.1578 μm up to 1.6410 μm against the irradiation dose. This means that nano-composites could be used to transmit optical data in low dispersion optical fibers.
•PVA/H2SO4/Ethanol films doped with Ag nano-particles are prepared.•Structural changes of as prepared films due to irradiation with Gamma rays are studied using XRD and optical absorbance.•Fitting absorption coefficient using Elliot model revealed that the direct is the most probable transition.•Single oscillator strength, oscillator dispersion energy and lattice oscillator strength Optical factors are calculated.•Zero material dispersion and its corresponding wavelength are considered and discussed as a function of irradiation doses.
In this work, the optical and mechanical properties of Fe
2
O
3
nanoparticles (NPs)/chitosan nanocomposite films have been investigated. Nanocomposite films of different weight ratios of Fe
2
O
3
...NPs/chitosan (0, 1, 5, 10, 20 and 30 wt%) were fabricated using casting technique. The optical properties of colloidal Fe
2
O
3
NPs and Fe
2
O
3
NPs/chitosan nanocomposite films were recorded using UV–visible spectrophotometer. As the ratio of Fe
2
O
3
NPs to chitosan increases from 0 to 30%, the energy band gap of Fe
2
O
3
NPs/chitosan films decreases from 3.16 to 2.11 eV. This decrease is due to quantum confinement effect. The mechanical properties of the nanocomposite films as a function of sweeping temperature were measured using a dynamic mechanical analyzer. An enhancement in storage modulus, stiffness and glass transition temperature (T
g
) has been observed as the ratio of Fe
2
O
3
NPs/chitosan increases. T
g
of Fe
2
O
3
NPs/chitosan nanocomposite film shifts towards higher temperature side with respect to pure chitosan film from 152.1 to 166.3 °C as the ratio of Fe
2
O
3
NPs/chitosan increases from 0 to 30 wt%. The increase in T
g
is mainly attributed to the decrease in free volumes and vacancies in the nanocomposite films as the weight ratio of Fe
2
O
3
NPs/chitosan increases.
The optical properties of a series of Se
100-x
Te
x
(
x
= 0, 1, 5, 10, 15, 20, 25 and 35) films have been determined using a variable angle spectroscopic ellipsometer in the photon energies range of ...1–5 eV. Se
100-x
Te
x
films were prepared by conventional vacuum deposition. The dielectric functions of this series are parameterized using a dielectric function model that applies two Cody–Lorentz (CL) and one Harmonic oscillator models. This parameterization scan is performed positively to define the changes in the optical properties with Te content. Lorentz oscillator amplitude (
A
fun
), oscillator width (
C
fun
), the extent of broadening
E
u
fun
and transition energy (
E
p
fun
) of the prepared films are enhanced with increasing Te content. While the CL peak transition energy (
E
o
fun
) and optical energy gap are gradually decreased as Te content is increased.
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