Enhanced lithium host performance of multi-walled carbon nanotubes through acidic functionalization for lithium-sulfur batteries.

Carbon nanotubes (CNTs) have been explored as a potential cathode material for lithium-sulfur (Li-S) batteries owing to their unique structure. However, traditional CNTs exhibit poor dispersion properties when preparing electrodes. The non-uniform distribution of the conductive agents hinders the formation of enough sites for sulfur loading, which results in the aggregation of sulfur/Li2S and severe polarization. In this study, we propose the acidic functionalization of CNTs in the cathode structure as a practical solution for mitigating the poor dispersion and polysulfide shuttling in lithium-sulfur batteries. Multiwalled CNTs were functionalized by oxidation through acidic treatment using sulfuric, nitric, and mixed acids. The cathode prepared with a mixture of sulfuric and nitric acids showed a coulombic efficiency of 99 % after 100 cycles, with a discharge capacity of 743 mAh g-1. These findings demonstrate the effectiveness of the acidic functionalization of CNTs as a promising approach for enhancing the electrochemical performance and commercial viability of lithium-sulfur batteries.

Identification of Novel Isatin Derivative Bearing a Nitrofuran Moiety as Potent Multi-Isoform Aldehyde Dehydrogenase Inhibitor.

Aldehyde dehydrogenases (ALDHs) are a family of enzymes that aid in detoxification and are overexpressed in several different malignancies. There is a correlation between increased expression of ALDH and a poor prognosis, stemness, and resistance to several drugs. Several ALDH inhibitors have been generated due to the crucial role that ALDH plays in cancer stem cells. All of these inhibitors, however, are either ineffective, very toxic, or have yet to be subjected to rigorous testing on their effectiveness. Although various drug-like compounds targeting ALDH have been reported in the literature, none have made it to routine use in the oncology clinic. As a result, new potent, non-toxic, bioavailable, and therapeutically effective ALDH inhibitors are still needed. In this study, we designed and synthesized potent multi-ALDH isoform inhibitors based on the isatin and indazole pharmacophore. Molecular docking studies and enzymatic tests revealed that among all of the synthesized analogs, compound 3 is the most potent inhibitor of ALDH1A1, ALDH3A1, and ALDH1A3, exhibiting 51.32%, 51.87%, and 36.65% inhibition, respectively. The ALDEFLUOR assay further revealed that compound 3 acts as an ALDH broad spectrum inhibitor at 500 nM. Compound 3 was also the most cytotoxic to cancer cells, with an IC50 in the range of 2.1 to 3.8 µM for ovarian, colon, and pancreatic cancer cells, compared to normal and embryonic kidney cells (IC50 7.1 to 8.7 µM). Mechanistically, compound 3 increased ROS activity due to potent multi-ALDH isoform inhibition, which increased apoptosis. Taken together, this study identified a potent multi-isoform ALDH inhibitor that could be further developed as a cancer therapeutic.

Synthesis of Binder-Free, Low-Resistant Randomly Orientated Nanorod/Sheet ZnS-MoS2 as Electrode Materials for Portable Energy Storage Applications.

The scientific community needs to conduct research on novel electrodes for portable energy storage (PES) devices like supercapacitors (S-Cs) and lithium-ion batteries (Li-ion-Bs) to overcome energy crises, especially in rural areas where no electrical poles are available. Herein, the nanostructured MoS2 and ZnS-MoS2 E-Ms consisting of nanoparticles/rods/sheets (N-Ps-Rs-Ss) are deposited on hierarchical nickel foam by a homemade chemical vapor deposition (H-M CVD) route. The X-ray diffraction patterns confirm the formation of polycrystalline films growing along various orientations, whereas the field-emission scanning electron microscope analysis confirms the formation of N-Ps-Rs-Ss. The change in structural and microstructural parameters indicates the existence of defects improving the energy storage ability of the deposited ZnS-MoS2@Ni-F electrodes. The specific capacitances of MoS2@Ni-F and ZnS-MoS2@Ni-F electrodes are found to be 1763 and 3565 F/g at 0.5 mV/s and 1451 and 3032 F/g at 1 A/g, respectively. The growing behavior of impedance graphs indicates their capacitive nature; however, the shifting of impedance curves toward y-axis indicates that the increasing diffusion rates due to the formation of nanostructures of ZnS-MoS2 results in low impedance. An excellent energy storage performance, minimum capacity fading, and improved electrical conductivity of the deposited E-Ms are due to the combined contributions of the electrical double layer and pseudocapacitor nature, which is again confirmed by theoretical Dunn's model. The absence of charge transfer resistance and good capacitance retention (95%) even after 10,000 cycles indicates that the deposited E-Ms are better for PES devices like S-Cs and Li-ion-Bs than MoS2 E-Ms. The assembled asymmetric supercapacitor device exhibited the maximum specific capacitance = 996 F/g, energy density = 354-285 W h/kg, power density = 2400-24,000 W/kg, capacitance retention = 95% and Coulombic efficiency = 100% even after a long charging-discharging of 10,000 cycles.

Design and characterization of phosphonic acid-functionalized grafted sepiolite nanohybrids and their adsorption studies for removal of copper ions from aqueous solution.

In this study, we synthesized novel, economically efficient phosphonic acid-functionalized grafted sepiolite nanohybrids for selective elimination of copper ions from water. These nanohybrids were prepared by graft polymerization of glycidyl methacrylate onto sepiolite. We utilized free radical graft polymerization to graft glycidyl methacrylate (GMA) onto silanized sepiolite. The nanohybrids obtained exhibited a grafting percentage of 479% at 0.3 g of KPS initiator, 15% GMA monomer, and after 4 h of reaction. In pursuit of selectively removing metal ions from water, the nanohybrid with the highest grafting (PGE3) was chemically treated with phosphoric acid to introduce phosphonic acid groups on it. FTIR, XRD, SEM, CHO analysis, BET, and TGA analysis were utilized to characterize the developed nanohybrids. Batch adsorption studies were carried out using AAS process, examining the impact of pH, adsorbent weight, contact time, adsorbate concentration, and temperature on the adsorption process. Due to the selectivity of phosphonic acid groups towards copper ions, phosphonic acid-functionalized grafted sepiolite nanohybrid (PGE3-P) was used for copper ions removal from its aqueous solution. The maximum adsorption capacity of PGE3-P adsorbents was 134.5 mg/g for copper ions. The data from kinetic studies suggests that the adsorption process of copper ions followed a pseudosecond-order model. Furthermore, Langmuir isotherm proved to be a more fitting model in equilibrium isothermal investigations. The thermodynamic analysis of the data indicates that the adsorption of copper ions by PGE3-P is an endothermic and spontaneous process. The development of this phosphonic acid-functionalized grafted sepiolite nanohybrid adsorbent is a new contribution into the field of adsorption. The developed material can be utilized as selective adsorbent for elimination of other heavy metals from water.

Identification of a Novel Protein Phosphatase 2A Activator, PPA24, as a Potential Therapeutic for FOLFOX-Resistant Colorectal Cancer.

A series of compounds were designed utilizing molecular modeling and fragment-based design based upon the known protein phosphatase 2A (PP2A) activators, NSC49L and iHAP1, and evaluated for their ability to inhibit the viability of colorectal cancer (CRC) and folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX)-resistant CRC cells. PPA24 (19a) was identified as the most cytotoxic compound with IC50 values in the range of 2.36-6.75 µM in CRC and FOLFOX-resistant CRC cell lines. It stimulated PP2A activity to a greater extent, displayed lower binding energies through molecular docking, and showed higher binding affinity through surface plasmon resonance for PP2A catalytic subunit α than the known PP2A activators. PPA24 dose-dependently induced apoptosis and oxidative stress, decreased the level of c-Myc expression, and synergistically potentiated cytotoxicity when combined with gemcitabine and cisplatin. Furthermore, a PPA24-encapsulated nanoformulation significantly inhibited the growth of CRC xenografts without systemic toxicities. Together, these results signify the potential of PPA24 as a novel PP2A activator and a prospective therapeutic for CRC and FOLFOX-resistant CRC.

Exploring Novel Coumarin-Tethered Bis-Triazoles: Apoptosis Induction in Human Pancreatic Cancer Cells, Antimicrobial Effects, and Molecular modelling Investigations.

In the present study, we identified that two representative compounds (7c and 9f) of our newly synthesized coumarin-tagged bis-triazoles induced apoptosis in human pancreatic cells (PANC-1) by caspase 3/7mediated pathway. Both 7c and 9f (IC50 = 7.15 ± 1.19 and 6.09 ± 0.79 µM, respectively) were found to be ~100 times superior against PANC-1 as compared to the standard drug Gemcitabine (IC50 = >500 µM), without showing any toxicity to the normal pancreatic epithelial cells (H6C7). Molecular docking studies further endorsed them as potential pancreatic cancer therapeutics due to their strong hydrogen bonding interactions with the epidermal growth factor receptor (EGFR) enzyme, which is overexpressed in cancerous cells including pancreatic cancer. Additionally, these compounds also showed moderate inhibitory activity against a panel of microbial strains. Overall, our findings reveal that the coumarin hybrids 7c and 9f are viable chemotypes to be adopted as templates for the development of new anticancer drugs, particularly against pancreatic cancer.

Heavy Metal Concentrations in Water, Sediment, and Fish Species in Chashma Barrage, Indus River: A Comprehensive Health Risk Assessment.

The increasing levels of heavy metals in aquatic environments, driven by human activities, pose a critical threat to ecosystems' overall health and sustainability. This study investigates the bioaccumulation of heavy metals (Pb, Cu, Cr, and Cd) in water, sediment, and three fish species (Catla catla, Labeo rohita, Cirrhinus mrigala) of different feeding zones within Chashma Barrage, located in the Mianwali district of Punjab, Pakistan, on the Indus River. A comprehensive analysis, including an assessment of associated human health risks, was conducted. Thirty samples from all three sites for each fish species, with an average body weight of 160 ± 32 g, were collected from Chashma Barrage. Water quality parameters indicated suitability for fish growth and health. Heavy metal concentrations were determined using an atomic absorption spectrometer. Results indicated elevated levels of Cd, Cr, and Cu in sediment and Pb and Cd in water, surpassing WHO standard limits. Among the fish species, bottom feeder (C. mrigala) exhibited significantly (P < 0.05) higher heavy metal levels in its tissues (gills, liver, and muscle) compared to column feeder (L. rohita) and surface feeder (C. catla). Liver tissues across all species showed higher heavy metal bioaccumulation, followed by gills. Principal component analysis (PCA) revealed strong correlations among heavy metals in sediment, gills, muscle, and water in every fish species. However, the vector direction suggests that Cr was not correlated with other heavy metals in the system, indicating a different source. The human health risk analysis revealed lower EDI, THQ, and HI values (< 1) for the fish species, indicating no adverse health effects for the exposed population. The study emphasizes the bioaccumulation differences among fish species, underscoring the higher heavy metal concentrations in bottom feeder fish within Chashma Barrage.

Ecological patterns of phytoplankton across lake cross-section: insights into co-evolution of physicochemical conditions in Chashma Lake on Indus River.

Physicochemical properties of water influence planktonic diversity and distribution, which is essential in obtaining basic knowledge of aquatic biodiversity. Thus current study aims to investigate the spatiotemporal diversity, abundance ratio, and distribution of phytoplankton species and their association with water quality parameters of Chashma Lake, Pakistan. During the study period from 2018 to 2019, we measured 13 physicochemical parameters across three selected sampling sites (S1, S2, and S3) in Chashma Lake, revealing both spatial and temporal variability. Dissolved oxygen (DO) was higher in S3, while S1 exhibited higher alkalinity levels, carbon dioxide, phosphorus, and chloride levels. The study identified 77 phytoplankton species grouped into five taxonomic categories, with Cyanobacteria dominating (39.90%), followed by Chlorophyta (33.4%) and Bacillariophyta (24.88%). Euglenozoa and Ochrophyta were less abundant (1.3% and 0.41%, respectively). Spatial variations in phytoplankton distribution were noted, with Chlorophyta being more abundant at S2, Bacillariophyta and Cyanobacteria at S1, and Euglenozoa dominating at S3. Canonical Correspondence Analysis (CCA) revealed the influence of various physicochemical parameters on phytoplankton distribution. This comprehensive study provides valuable insights for the ecological assessment and monitoring of water bodies. It is recommended that continuous monitoring is required to capture long-term trends, further explore the specific environmental drivers impacting phytoplankton dynamics, and consider management strategies for maintaining water quality and biodiversity in Chashma Lake.

Thermal stability analysis of nitrile additives in LiFSI for lithium-ion batteries: An accelerating rate calorimetry study.

Although lithium-ion batteries (LIBs) are extensively used as secondary storage energy devices, they also pose a significant fire and explosion hazard. Subsequently, thermal stability studies for LiPF6- and LiFSI-type electrolytes have been conducted extensively. However, the thermal characteristics of these electrolytes with thermally stable additives in a full cell assembly have yet to be explored. This study presents a comprehensive accelerating rate calorimetry (ARC) study. First, 1.2-Ah cells were prepared using a control commercial LiPF6 electrolyte and LiFSI with a specific succinonitrile additive and ethyl-methyl carbonate as a thermally stable electrolyte additive. The kinetic parameters involved in heat generation and their effects on the thermal properties of the ARC module were analyzed from the heat-wait-seek (HWS), self-heating (SH), and thermal runaway (TR) stages. The results indicate that the addition of a succinonitrile additive to the LiFSI electrolyte lowers the decomposition temperatures of the solid electrolyte interface (SEI) owing to polymerization with Li at the anode, while simultaneously increasing the activation energy of reaction temperatures at SEI between the separator and the electrolyte. The maximum thermal-runaway temperature decreased from 417 °C (ΔH = 5.26 kJ) (LiPF6) to 285 °C (ΔH = 2.068 kJ) (LiFSI + succinonitrile). This study provides key insights to the thermal characteristics of LiPF6 and LiFSI during the self-heating and thermal runaway stages and indicates a practical method for achieving thermally stable LIBs.

Boosted photocatalytic hydrogen evolution of S-scheme N-doped CeO2-δ@ZnIn2S4 heterostructure photocatalyst.

The advancement of highly effective heterojunction photocatalysts with improved charge separation and transfer has become a crucial scientific perspective for utilizing solar energy. In this study, we developed the S-scheme heterostructure by depositing N-doped CeO2-δ (NC) nanoparticles onto two-dimensional ZnIn2S4 (ZIS) nanosheets via hydrolysis strategy for significantly enhanced photocatalytic hydrogen evolution reaction. The optimal H2 generation rate of âˆ¼ 798 µmol g-1 h-1 was achieved for NC-3@ZIS under solar light irradiation, which is about 18 and 2 times higher than those of pristine CeO2 (∼44 µmol g-1 h-1) and ZIS (∼358 µmol g-1 h-1), respectively. The photogenerated electrons from NC interact with the photogenerated holes of ZIS driven by an internal electric field, confirmed by In-situ KPFM, DFT calculation, and XPS results. According to EPR and photoelectrochemical measurements, NC-3@ZIS composite shows dramatically high separation efficiency of photogenerated charge carriers. This study provides a new approach for developing non-noble metal S-scheme heterojunctions with enhanced photocatalytic hydrogen evolution.

Rational Design and Synthesis of Isatin-Chalcone Hybrids Integrated with 1H-1,2,3-Triazole: Anti-Proliferative Profiling and Molecular Docking Insights.

In this study, a series of isatin-chalcone linked triazoles were synthesized using Cu-promoted Azide-Alkyne Cycloaddition (CuAAC) reaction and evaluated for their cytotoxicity against various cancer cell lines. The most potent compound displayed approximately 2.5 times greater activity compared to both reference compounds against ovarian cancer cell lines. These findings were supported by caspase-mediated apoptosis and molecular docking analyses. Docking revealed comparable VEGFR-2 affinities for 5 b and 5-FU but highlighted stronger interaction of 5 b with EGFR, evident from its lower docking score. Overall, these results signify the notable anti-proliferative potential of most synthesized hybrids, notably emphasizing the efficacy of compound 5 b in suppressing cancer cell growth.

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents.

We designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, 1 H NMR, 13 C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT-116), breast cancer (MDA-MB-231), prostate cancer (DU-145), and one normal cell line: human embryonic kidney cell line (HEK-293). The obtained results indicate that two compounds, FQ and MQ, with IC50 values < 16 µM, were the most active compounds. Molecular docking studies revealed the binding of FQ and MQ molecules in the active site of the c-Met kinase (PDB ID: 3F66, 1.40 Å). Furthermore, QikProp ADME prediction and the MDS analysis preserved those critical docking data of both compounds, FQ and MQ. Western blotting was used to confirm the impact of the compounds FQ and MQ on the inhibition of the c-Met kinase receptor. The apoptosis assays were performed to investigate the mechanism of cell death for the most active compounds, FQ and MQ. The Annexin V/7-AAD assay indicated apoptosis in MDA-MB-231 cells treated with FQ and MQ, with FQ (21.4%) showing a higher efficacy in killing MDA-MB-231 cells than MQ (14.25%). The Caspase 3/7 7-AAD assay further supported these findings, revealing higher percentages of apoptotic cells for FQ-treated MDA-MB-231 cells (41.8%). The results obtained from the apoptosis assay conclude that FQ exhibits better anticancer activity against MDA-MB-231 cells than MQ.

Sublethal Concentrations of Cadmium and Lead: Effects on Hemato-Biochemical Parameters and Tissue Accumulation in Wallagu attu.

The exposure of fish to heavy metals can significantly impact physiological processes and potentially lead to adverse health effects. This study assesses the effects of exposure to Cd and Pb sublethal concentrations in water on Wallagu attu. A total of 48 fish with an average body weight of 145.5 ± 26 g were distributed among three groups (control, Cd-treated, and Pb-treated) within 60 L fiberglass tanks. They were exposed to 30% sublethal concentrations of Cd and Pb for durations of 1, 15, and 30 days. Following this exposure, an assessment was conducted on metal bioaccumulation and hemato-biochemical responses. Results revealed a significantly (P < 0.05) higher concentration of heavy metals in the fish tissues of metals exposed groups than in the control. The concentration of Cd and Pb increases in fish tissues (kidney > gills > intestine) with exposure time. In most cases, the Pb-exposed group exhibited significantly (P < 0.05) higher concentrations of Pb in different tissues than the Cd-treated group. With extended exposure time, the activities of CAT and SOD show a significant decrease in both Cd and Pb-treated groups. However, the reduction in activities was more pronounced in the Cd-exposed group. On 15 and 30 days, the levels of red blood cells (RBC), hemoglobin (HB), hematocrit (HCT), and total protein (TP) decrease in groups exposed to Cd and Pb. The cortisol and glucose levels exhibit a more noticeable (P < 0.05) increase with prolonged exposure to Cd and Pb than the control group. On day 30, the survival rate decreased more in the Pb-exposed group. The findings of this study indicate that exposure to sublethal doses of Cd and Pb induces stress in Wallagu attu, resulting in rapid changes in specific hemato-biochemical parameters.

Downsizing Porphyrin Covalent Organic Framework Particles Using Protected Precursors for Electrocatalytic CO2 Reduction.

Covalent organic frameworks (COFs) are promising electrocatalyst platforms owing to their designability, porosity, and stability. Recently, COFs with various chemical structures are developed as efficient electrochemical CO2 reduction catalysts. However, controlling the morphology of COF catalysts remains a challenge, which can limit their electrocatalytic performance. Especially, while porphyrin COFs show promising catalytic properties, their particle size is mostly large and uncontrolled because of the severe aggregation of crystallites. In this work, a new synthetic methodology for rationally downsized COF catalyst particles is reported, where a tritylated amine is employed as a novel protected precursor for COF synthesis. Trityl protection provides high solubility to a porphyrin precursor, while its deprotection proceeds in situ under typical COF synthesis conditions. Subsequent homogeneous nucleation and colloidal growth yield smaller COF particles than a conventional synthesis, owing to suppressed crystallite aggregation. The downsized COF particles exhibit superior catalytic performance in electrochemical CO2 reduction, with higher CO production rate and faradaic efficiency compared to conventional COF particles. The improved performance is attributed to the higher contact area with a conductive agent. This study reveals particle size as an important factor for the evaluation of COF electrocatalysts and provides a strategy to control it.

Seleno-Warfare against Cancer: Decoding Antitumor Activity of Novel Acylselenoureas and Se-Acylisoselenoureas.

Currently, cancer remains a global health problem. Despite the existence of several treatments, including chemotherapy, immunotherapy, and radiation therapy, the survival rate for most cancer patients, particularly those with metastasis, remains unsatisfactory. Thus, there is a continuous need to develop novel, effective therapies. In this work, 22 novel molecules containing selenium are reported, including seven Se-acylisoselenoureas synthesized from aliphatic carbodiimides as well as acylselenoureas with the same carbo- and heterocycles and aliphatic amines. After an initial screening at two doses (50 and 10 µM) in MDA-MB-231 (breast), HTB-54 (lung), DU-145 (prostate), and HCT-116 (colon) tumor cell lines, the ten most active compounds were identified. Additionally, these ten hits were also submitted to the DTP program of the NCI to study their cytotoxicity in a panel of 60 cancer cell lines. Compound 4 was identified as the most potent antiproliferative compound. The results obtained showed that compound 4 presented IC50 values lower than 10 µM in the cancer cell lines, although it was not the most selective one. Furthermore, compound 4 was found to inhibit cell growth and cause cell death by inducing apoptosis partially via ROS production. Overall, our results suggest that compound 4 could be a potential chemotherapeutic drug for different types of cancer.

Isatin-indoloquinoxaline click adducts with a potential to overcome platinum-based drug-resistance in ovarian cancer.

Herein, a series of isatin tethered indolo[2,3-b]quinoxaline hybrids was synthesized by considering the pharmacophoric features of known DNA intercalators and topoisomerase II inhibitors. The anti-proliferative properties of the synthesized compounds were evaluated against ovarian cancer cell lines (SKOV-3 and Hey A8). Four of the compounds exhibited promising anti-proliferative activities, with one of them being 10-fold more potent than cisplatin against drug-resistant Hey A8 cells. Further investigations were carried out to determine the DNA intercalating affinities of the most active compounds as potential mechanisms for their anti-proliferative activities. ADMET in silico studies were performed to assess the physicochemical, pharmacokinetics, and toxicity parameters of active compounds. This study, to the best of our knowledge, is the first report on the potential of isatin-indoloquinoxaline hybrids as structural blueprints for the development of new DNA intercalators. Additionally, it explores their potential to circumvent platinum-based resistance in ovarian cancer.

Stereo/regio-selective access to substituted 3-hydroxy-oxindoles with anti-proliferative assessment and in silico validation.

The manuscript focuses on a highly stereo-/regioselective approach for synthesizing a diverse array of substituted-3-hydroxy-2-oxindoles. The synthesized compounds were subsequently subjected to anti-proliferative assessment against various cell lines, including colorectal carcinoma, ovarian cancer, and human metastatic melanoma cancer. The structural characterization of the synthesized scaffolds was unambiguously confirmed using X-ray diffraction analysis. Among the synthesized compounds, one compound demonstrated exceptional potency within the series. It exhibited 1.2, 2.12, and 1.55 times greater potency than cisplatin against the HCT116, OVCAR10, and 1205Lu cell lines, respectively. These results were further supported by in vitro caspase-mediated apoptosis studies. Molecular docking studies of these compounds on the target VEGFR2 protein revealed their binding capability.

Current understanding of structural and molecular changes in diabetic cardiomyopathy.

Diabetic Mellitus has been characterized as the most prevalent disease throughout the globe associated with the serious morbidity and mortality of vital organs. Cardiomyopathy is the major leading complication of diabetes and within this, myocardial dysfunction or failure is the leading cause of the emergency hospital admission. The review is aimed to comprehend the perspectives associated with diabetes-induced cardiovascular complications. The data was collected from several electronic databases such as Google Scholar, Science Direct, ACS publication, PubMed, Springer, etc. using the keywords such as diabetes and its associated complication, the prevalence of diabetes, the anatomical and physiological mechanism of diabetes-induced cardiomyopathy, the molecular mechanism of diabetes-induced cardiomyopathy, oxidative stress, and inflammatory stress, etc. The collected scientific data was screened by different experts based on the inclusion and exclusion criteria of the study. This review findings revealed that diabetes is associated with inefficient substrate utilization, inability to increase glucose metabolism and advanced glycation end products within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity, and initially subclinical cardiac dysfunction and finally in overt heart failure. Furthermore, several factors such as hypertension, overexpression of renin angiotensin system, hypertrophic obesity, etc. have been seen as majorly associated with cardiomyopathy. The molecular examination showed biochemical disability and generation of the varieties of free radicals and inflammatory cytokines and becomes are the substantial causes of cardiomyopathy. This review provides a better understanding of the involved pathophysiology and offers an open platform for discussing and targeting therapy in alleviating diabetes-induced early heart failure or cardiomyopathy.

First Generation of Antioxidant Precursors for Bioisosteric Se-NSAIDs: Design, Synthesis, and In Vitro and In Vivo Anticancer Evaluation.

The introduction of selenium (Se) into organic scaffolds has been demonstrated to be a promising framework in the field of medicinal chemistry. A novel design of nonsteroidal anti-inflammatory drug (NSAID) derivatives based on a bioisosteric replacement via the incorporation of Se as diacyl diselenide is reported. The antioxidant activity was assessed using the DPPH radical scavenging assay. The new Se-NSAID derivatives bearing this unique combination showed antioxidant activity in a time- and dose-dependent manner, and also displayed different antiproliferative profiles in a panel of eight cancer cell lines as determined by the MTT assay. Ibuprofen derivative 5 was not only the most antioxidant agent, but also selectively induced toxicity in all the cancer cell lines tested (IC50 < 10 µM) while sparing nonmalignant cells, and induced apoptosis partially without enhancing the caspase 3/7 activity. Furthermore, NSAID derivative 5 significantly suppressed tumor growth in a subcutaneous colon cancer xenograft mouse model (10 mg/kg, TGI = 72%, and T/C = 38%) without exhibiting any apparent toxicity. To our knowledge, this work constitutes the first report on in vitro and in vivo anticancer activity of an unprecedented Se-NSAID hybrid derivative and its rational use for developing precursors for bioisosteric selenocompounds with appealing therapeutic applications.