Unraveling the Ties: Type 2 Diabetes and Parkinson's Disease - A Nano-Based Targeted Drug Delivery Approach.

The link between Type 2 Diabetes (T2DM) and Parkinson's Disease (PD) dates back to the early 1960s, and ongoing research is exploring this association. PD is linked to dysregulation of dopaminergic pathways, neuroinflammation, decreased PPAR-γ coactivator 1-α, increased phosphoprotein enriched in diabetes, and accelerated α-Syn amyloid fibril production caused by T2DM. This study aims to comprehensively evaluate the T2DM-PD association and risk factors for PD in T2DM individuals. The study reviews existing literature using reputable sources like Scopus, ScienceDirect, and PubMed, revealing a significant association between T2DM and worsened PD symptoms. Genetic profiles of T2DM-PD individuals show similarities, and potential risk factors include insulin-resistance and dysbiosis of the gut-brain microbiome. Anti-diabetic drugs exhibit neuroprotective effects in PD, and nanoscale delivery systems like exosomes, micelles, and liposomes show promise in enhancing drug efficacy by crossing the Blood-Brain Barrier (BBB). Brain targeting for PD uses exosomes, micelles, liposomes, dendrimers, solid lipid nanoparticles, nano-sized polymers, and niosomes to improve medication and gene therapy efficacy. Surface modification of nanocarriers with bioactive compounds (such as angiopep, lactoferrin, and OX26) enhances α-Syn conjugation and BBB permeability. Natural exosomes, though limited, hold potential for investigating DM-PD pathways in clinical research. The study delves into the underlying mechanisms of T2DM and PD and explores current therapeutic approaches in the field of nano-based targeted drug delivery. Emphasis is placed on resolved and ongoing issues in understanding and managing both conditions.

A comparative performance evaluation of cephalosporin's drugs for fluoride recognition.

In this manuscript, readily available cephalosporin's drugs cefuroxime axetil (L1) cefpdoxime proxetil (L2), and cefditoren pivoxil (L3) possess dihydrothiazine ring as signaling unit, and -NH groups as the binding site were used for the sensing of fluoride (F-) ions. In the presence of F-, the drug selectively portrayed a naked-eye detectable color change from colorless. The binding constant of 1:1 stoichiometric complex of L1, L2, and L3 with F- was found to be 2.36 × 104 M-1, 2.44 × 103 M-1 and 1.02 × 104 M-1 respectively. The lowest detection limit (LOD) of F- was found to be 11 µM (209 ppb) with drug L1 and L2. The binding mechanism of the drug with F- was studied by 1H and 19F nuclear magnetic resonance (NMR) spectral titration, electrospray ionization mass spectra (ESI-MS) analysis, and density functional theory (DFT) studies. The presence of F- was monitored in various spiked water and Colgate toothpaste samples. Overall, cephalosporin's drug demonstrates a promising potential for the detection of F- ions in the semi-aqueous phase.

In vitro studies on the selective cytotoxic effect of luminescent Ru(II)-p-cymene complexes of imidazo-pyridine and imidazo quinoline ligands.

In recent years, Ru(II) complexes have gained high importance in medicinal chemistry due to their significant anti-cancer activities, which are directly related to their DNA binding ability. In this report, the chemistry and cytotoxicity of two new Ru(II) complexes containing imidazole pyridine (Ru-1) and imidazole quinoline (Ru-2) have been studied. The prepared compounds were characterized using infrared (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS), isothermal titration calorimetry (ITC), UV-Vis, and fluorescence spectral techniques. The structural analyses show that the Ru(II) complexes exhibit a 'piano stool' coordination geometry and they are composed of one bound arene, two sigma bonded benzil nitrogen atoms, and labile chlorine linked to Ru(II). The photo-physical properties of these complexes were examined, and they exhibit absorption peaks at 260 nm and 380 nm, which are due to the involvement of intra-ligand charge transitions (ILCT) and metal-to-ligand charge transitions (MLCT), respectively. The binding process of the Ru(II) complexes with DNA and BSA is non-covalent in nature and the binding constants of Ru-1 and Ru-2 complexes with DNA and BSA were found to be 1 × 105 M-1 and 1 × 103 M-1, respectively. In the presence of the Ru(II) complexes, ethidium bromide (EtBr) is competitively displaced from DNA by intercalation of the Ru(II) complexes in DNA and it is well corroborated by viscosity and in silico studies. Both the ligands and Ru(II) complexes were carefully investigated in vitro for cytotoxicity against HeLa, MCF-7, and MDA-MB-231 cells. Surprisingly, both Ru(II) complexes exhibit superior cytotoxicity to cisplatin with a low LD50 value against the examined cancer cells. Besides, an insignificant effect on HEK normal cells (LD50 > 140 µM) was observed.

Pyridine: the scaffolds with significant clinical diversity.

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

Iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol analogues as hypoxia active, GSH-resistant cancer cytoselective and mitochondria-targeting cancer stem cell therapeutic agents.

Herein, we have introduced a series of iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [IrIII(Cp*)(L5)(Cl)](PF6) (IrL5) complex exhibited the best cytoselectivity, GSH resistance and hypoxia effectivity in HeLa and Caco-2 cells among the synthesized complexes. IrL5 also exhibited highly cytotoxic effects on the HCT-116 CSC cell line. This complex was localized in the mitochondria and subsequent mitochondrial dysfunction was observed via MMP alteration and ROS generation on colorectal cancer stem cells. Cell cycle analysis also established the potential of this complex in mediating G2/M phase cell cycle arrest.

A quinoline-benzothiazole-based chemosensor coupled with a smartphone for the rapid detection of In3+ ions.

A newly designed quinoline-benzothiazole probe 2-((Z)-((E)-benzo[d]thiazol-2(3H)-ylidenehydrazono)methyl)quinolin-8-ol (L) was synthesized by reacting 8-hydroxyquinoline-2-carbaldehyde with 2-hydrazinobenzothiazole and structurally characterized by various spectroscopic techniques. The sensing ability of probe L was studied with various cations using colorimetry, test paper strips, a red-green-blue (RGB) model and UV-visible spectrophotometry in DMSO : H2O (3 : 7, v/v). The pale yellow colour of L turns into orange on contact with In3+ ions, whereas other tested metal ions did not show any change in colour. The probe L exhibits an absorbance band at 360 nm due to ligand-to-ligand charge transfer (LLCT); upon interaction with In3+ ions, it exhibits a band at 445 nm due to ligand-to-metal charge transfer (LMCT). The probe L binds In3+ in a 2 : 1 ratio with an association constant of 8.1 × 105 M-1 and this is established using the Job's and Benesi-Hildebrand (B-H) methods. The probe L can work in the pH range of 4-8 without interfering with other competing ions. It can be used to detect quantities as low as 2.3 ppb and 85 ppb by spectrophotometry and RGB, respectively. The binding mechanism was studied by 1H NMR titration, ESI mass and FT-IR spectral analysis and well supported by theoretical studies. Overall, probe L demonstrates promising potential for the detection of In3+ ions in the semi-aqueous phase and this is its first report as a colorimetric chromogenic probe.

Rapid detection strategies for the ultra-level chemosensing of uranyl ions.

A simple and reliable colorimetric probe N,N'-bis-(4-diethylamino-2-hydroxybenzylidene)-1,10-phenanthroline-2,9-carbohydrazide (L) has been synthesised by reacting 4-(diethylamino)salicylaldehyde with 1,10-phenanthroline-2,9-dicarbohydrazide. The sensing ability of L was studied by its interactions with various f-block metal ions and other selected metal ions from s- and d-block by colorimetry, UV-visible spectrophotometry, and smartphone integrated red-green-blue (RGB) model in DMSO : H2O (7 : 3, v/v). The pale-yellow colour of L turns to wine-red upon interaction with uranyl ions (UO22+) and yellow-orange in the presence of Th4+, Zr4+, Fe3+, and Lu3+ ions. Other tested metal ions did not show any colour change of L. This color change offered a simple, quick, and consistent method for the selective and sensitive visual detection of trace levels of UO22+ ions without any need for sophisticated instruments. Sensor L exhibits two absorption bands at 358 and 389 nm due to ligand-to-ligand charge transfer (LLCT). Upon interaction of L with UO22+ and Th4+ ions, absorption bands are exhibited at 480 nm and 422 nm, respectively, due to ligand-to-metal charge transfer (LMCT). The UV-vis spectral studies indicated the formation of a 1 : 2 ligand-to-metal complex between L and UO22+ with an estimated association constant of 1.0 × 104 M-2. Using L, the concentration of UO22+ can be detected as low as 73 nM and 150 nM by spectrophotometry and RGB methods, respectively, without any interference from other tested ions with an RSD < 5% (n = 3). The binding mechanism was studied by 1H NMR titration, ESI mass, and FT-IR spectral analysis and was well supported by theoretical results. Overall, sensor L demonstrates promising analytical applicability for the detection of UO22+ ions in a semi-aqueous medium.

A turn-on fluorescent probe for Lu3+ recognition and bio-imaging in live cells and zebrafish.

A new Lu3+ selective fluorescent probe L was synthesized and characterized. The optical properties of L were investigated by using absorption and fluorescence spectral studies in 7 : 3 (v/v) aqueous dimethyl sulphoxide. Upon addition of Lu3+ in a pH 4 (acetate buffer) solution of L, the weakly fluorescent probe L became highly fluorescent. The fluorescence intensity increased five-fold at 490 nm with excitation at 437 nm. The formation of 2 : 1 complexation between L and Lu3+ was confirmed by Job's plot. The binding constant (Ka, 1.43 × 104 M-1) was determined by the Benesi-Hildebrand (BH) method. The limit of detection (LOD) of Lu3+ using L was found to be 23 nM. The binding mechanism of L with Lu3+ was studied by 1H-NMR, ESI mass spectroscopy, and theoretical studies. Further, the probe L was successfully used to bioimage Lu3+ in a zebrafish gill cell line (DrG) and in the yolk, papillae of the eyes, and head of zebrafish embryos (Danio rerio), therefore providing a powerful live imaging approach for investigating chemical signaling in complex multicellular systems.

Critical Role of Dipeptidyl Peptidase IV: A Therapeutic Target for Diabetes and Cancer.

Diabetes mellitus is an emerging predator and affecting around 422 million adults worldwide. Higher levels of circulating insulin and increased pressure on the pancreas to produce insulin have been inferred as possible etiology for diabetes leading to a higher risk of pancreatic cancer. Out of several drug targets in hypoglycemic discovery, Dipeptidyl peptidase-IV (DPP-IV) has been considered an emerging target. It is a protease enzyme which inactivates incretin hormones i.e., Glucagonlike peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP). Inhibition of DPP-4 results in the longer action of GLP-1 and GIP, therefore, DPP-4 inhibitors play an important role in maintaining glucose homeostasis. In comparison to early oral hypoglycemic, DPP-IV inhibitors are well tolerated and provide a better glycemic control over a longer period. These enzymes are expressed in a dimeric form on the surface of different cells such as prostate, liver and small intestinal epithelium cells. Disruption of the local signaling environment is an emerging factor in cancer development. Till date, not even a single DPP-IV inhibitor as anticancer has been developed. This review focuses on various features of the enzyme and their suitable inhibitors for target disease.

Visible-light-induced degradation of rhodamine B by nanosized Ag2S-ZnS loaded on cellulose.

In the present work, new visible-light-active nanosized Ag2S-ZnS loaded on cellulose (AZCE) was synthesized by a precipitation method. The AZCE composite was systematically characterized using powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area, and UV-visible diffuse reflectance spectroscopy (UV-DRS). The activities of the photocatalysts were evaluated for rhodamine B dye (RhB) degradation under simulated sunlight and the amounts of the dye samples were analysed using a UV-vis spectrophotometer at λmax 554 nm. The effects of the reaction conditions such as pH, catalyst, hydrogen peroxide and dye concentration on the photodegradation rate have been investigated. The degradation profile reveals that 30 ppm of the dye could be effectively oxidized using 30 mg of the AZCE dose in the pH range 4-12 within 90 min. The oxidation of the RhB dye follows first-order kinetics and the rate constant was calculated to be 6.4 × 10-3 min-1. Various organic intermediates were identified during degradation using high performance liquid chromatography (HPLC), total organic content (TOC) and electron-spray ionization-mass spectrometry (ESI-MS). In order to determine the effectiveness of AZCE photocatalytic activity, other catalysts such as Ag2S loaded on cellulose (AZE) and ZnS loaded on cellulose (ZCE) were used as photocatalysts. The results show that photocatalytic activity follows the order AZCE > ACE > ZCE and this is due to the fact that a cellulose network is used as a catalyst carrier. The alkali pre-treated cellulose provides an activated surface hydroxyl groups to enhance the deposition efficiencies of Ag2S and ZnS and thereby a large amount of visible light can be absorbed and the photocatalytic activity is increased.

Development of the Smartphone-Assisted Colorimetric Detection of Thorium by Using New Schiff's Base and Its Applications to Real Time Samples.

In this paper, a new Th4+ ion-selective chromogenic sensor (L) was developed by reacting 1,10-phenanthroline-2,9-dicarbohydrazide with 2-hydroxy naphthaldehyde. The sensing ability of L toward Th4+ was investigated in solution and paper strips loaded with L using spectrophotometric and colorimetric methods. The selective interaction of L was examined with various f-metal ions and other selected metal ions from s-block and d-block elements. Results show that by the colorimetric method in solution-phase dimethyl sulfoxide/H2O (7:3, v/v) and paper strip methods, the naked-eye detectable color change of L occurred from colorless solution to yellow-orange and pale yellow colour upon interacting with Th4+ and Al3+, respectively, whereas other metal ions did not interfere. The ligand L exhibits two absorbance bands at 320 and 375 nm because of ligand-to-ligand charge transfer. Upon interaction with Th4+, L undergoes red shift of both absorption bands and the formation of a new UV-vis band at 335 and 440 nm. The UV-visible spectral studies indicate the formation of a 1:1 host-guest complex between L and Th4+ with an association constant of 4.7 × 103 M-1. The limit of quantification and limit of detection of L for the analysis of Th4+ are found to be 167 and 50 nM, respectively. The visually detectable color change of L has been well integrated with a smartphone RGB color value to make it an analytical signal for real-time analysis of Th4+ with the detection limit down to 116 nM. Besides, L was applied for the analysis of Th4+ content present in various real water samples, monazite, and lantern mantle samples by spectrophotometry and RGB color values. The binding mode of L with Th4+ is investigated by 1H NMR, electrospray ionization-mass, and theoretical studies.

PVC-based dicyclohexano-18-crown-6 sensor for La(III) ions.

A new ion-selective electrode (ISE) based on dicyclohexano-18-crown-6 (DC18C6) as a neutral carrier is developed for lanthanum(III) ions. The electrode comprises of dicyclohexano-18-crown-6 (6%), PVC (33%), and ortho-nitrophenyl octyl ether (o-NPOE) (61%). The electrode shows a linear dynamic response in the concentration range of 10(-6) to 10(-1)M with a Nernstian slope of 19mV per decade and a detection limit as 5x10(-7)M. It has a response time of <30s and can be used for at least 5 months without any significant divergence in potentials. The selectivity coefficients for mono-, di-, and trivalent cations indicate good selectivity for La(III) ions over a large number of interfering cations. The sensor has been used as an indicator electrode in the potentiometric titrations of La(III) with EDTA. The membrane is successfully applied in partially non-aqueous medium. It can be used in the pH range 4-9.