Combined effects of vitamin D3 and dioxopiperidinamide derivative on lipid homeostasis, inflammatory pathways, and redox imbalance in non-alcoholic fatty liver disease in vivo zebrafish model.

Liver damage and metabolic dysfunctions, the defining features of non-alcoholic fatty liver disease (NAFLD), are marked by inflammation, oxidative stress, and excessive hepatic fat accumulation. The current therapeutic approaches for NAFLD are limited, necessitating exploring novel treatment strategies. Dioxopiperidinamide derivatives, particularly DOPA-33, have shown effective anti-inflammatory and antioxidant properties, potentially offering therapeutic benefits against NAFLD.

Parental (F0) exposure to Cadmium and Ketoprofen induces developmental deformities in offspring (F1): A transgenerational toxicity assessment in zebrafish model.

In the aquatic environment, the primary pollutants of heavy metals and pharmaceuticals always occur in coexisting forms, and the research about combined impacts remains unclear, especially transgenerational effects. Cadmium (Cd) is a heavy metal that can damage the endocrine reproduction systems and cause thyroid dysfunction in fish. Meanwhile, ketoprofen (KPF) is a nonsteroidal anti-inflammatory drug (NSAID) that can cause neurobehavioral damage and physiological impairment.

Toxicity and therapeutic property of dioxopiperidin derivative SKT40 demonstrated in-vivo zebrafish model due to inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses chronic disorders that cause severe inflammation in the digestive tract. This study evaluates (E)-3-(3,4-dichlorophenyl)-N-(2,6-dioxopiperidin-3-yl) acrylamide (named SKT40), a derivative of dioxopiperidinamide, as a potential novel treatment for IBD. The pharmacological activity of SKT40 indicated positive interactions using network pharmacology and molecular docking in silico.

Co-occurrence of azorubine and bisphenol A in beverages increases the risk of developmental toxicity: A study in zebrafish model.

The prevalent use of Azorubine (E122) and the unintentional food additive, Bisphenol A (BPA), in ready-to-drink (RTD) beverages raises significant health concerns, especially for children. The combined impact on embryonic development must be explored despite individual safety assessments. Our investigation revealed that the combined exposure of E122 and BPA at beverage concentration significantly induces mortality and morphological deformities, including reduced growth, pericardial edema, and yolk sac edema.

Cadmium and ketoprofen accumulation influences aquatic ecosystem demonstrated using zebrafish model.

The growing concern about pollution and toxicity in aquatic as well as terrestrial organisms is predominantly caused due to waterborne exposure and poses a risk to environmental systems and human health. This study addresses the co-toxic effects of cadmium (Cd) and ketoprofen (KPF), representing heavy metal and pharmaceutical discharge pollutants, respectively, in aquatic ecosystems. A 96-h acute toxicity assessment was conducted using zebrafish embryos.

Indole-3-acetic acid induced cardiogenesis impairment in in-vivo zebrafish via oxidative stress and downregulation of cardiac morphogenic factors.

Plant growth regulators (PGRs) are increasingly used to promote sustainable agriculture, but their unregulated use raises concerns about potential environmental risks. Indole-3-acetic acid (IAA), a commonly used PGR, has been the subject of research on its developmental toxicity in the in-vivo zebrafish model. IAA exposure to zebrafish embryos caused oxidative stress, lipid peroxidation, and cellular apoptosis.

Beneficial Effects of PIN1 Inhibition on Diabetes Mellitus: A Concise Review.

Type 2 diabetes mellitus is a long-term medical illness in which the body either becomes resistant to insulin or fails to produce it sufficiently. Mostly, combinatorial therapy is required to control blood glucose levels. However, combinatorial therapy has detrimental side effects.

Daidzein ameliorates nonmotor symptoms of manganese-induced Parkinsonism in zebrafish model: Behavioural and biochemical approach.

Background And Purpose: Parkinson's disease (PD) is a prevalent neurodegenerative movement disorder characterized by motor dysfunction. Environmental factors, especially manganese (Mn), contribute significantly to PD. Existing therapies are focused on motor coordination, whereas nonmotor features such as neuropsychiatric symptoms are often neglected.

Identification of novel CA IX inhibitor: Pharmacophore modeling, docking, DFT, and dynamic simulation.

Human Carbonic anhydrase IX (hCA IX) is found to be an essential biomarker for the treatment of hypoxic tumors in both the early and metastatic stages of cancer. Due to its active function in maintaining pH levels and overexpression in hypoxic conditions, hCA IX inhibitors can be a potential candidate specifically designed to target cancer development at various stages. In search of selective hCA IX inhibitors, we developed a pharmacophore model from the existing natural product inhibitors with IC values less than 50 nm.

Dual Anti-Inflammatory and Anticancer Activity of Novel 1,5-Diaryl Pyrazole Derivatives: Molecular Modeling, Synthesis, In Vitro Activity, and Dynamics Study.

A series of novel 1,5-diaryl pyrazole derivatives targeting the COX enzyme were designed by combined ligand and structure-based approach. The designed molecules were then further subjected to ADMET and molecular docking studies. Out of 34 designed compounds, the top-10 molecules from the computation studies were synthesized, characterized, and evaluated for COX-2 inhibition and anti-cancer activity.

Neuroprotective potential of pyrazole benzenesulfonamide derivative T1 in targeted intervention against PTZ-induced epilepsy-like condition in in vivo zebrafish model.

Epilepsy is a chronic neurological disease characterized by a persistent susceptibility to seizures. Pharmaco-resistant epilepsies, impacting around 30 % of patients, highlight the urgent need for improved treatments. Neuroinflammation, prevalent in epileptogenic brain regions, is a key player in epilepsy, prompting the search for new mechanistic therapies.

Furan-based Chalcone Annihilates the Multi-Drug-Resistant Pseudomonas aeruginosa and Protects Zebra Fish Against its Infection.

The emergence of carbapenem-resistant Pseudomonas aeruginosa, a multi-drug-resistant bacteria, is becoming a serious public health concern. This bacterium infects immunocompromised patients and has a high fatality rate. Both naturally and synthetically produced chalcones are known to have a wide array of biological activities.

Exploring cyclin-dependent kinase inhibitors: a comprehensive study in search of CDK-6 inhibitors using a pharmacophore modelling and dynamics approach.

Cancer prevalence and resistance issues in cancer treatment are a significant public health concern globally. Among the existing strategies in cancer therapy, targeting cyclin-dependent kinases (CDKs), especially CDK-6 is found to be one of the most promising targets, as this enzyme plays a pivotal role in cell cycle stages and cell proliferation. Cell proliferation is the characteristic feature of cancer giving rise to solid tumours.

Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).

AIDS (acquired immunodeficiency syndrome) is a potentially life-threatening infectious disease caused by human immunodeficiency virus (HIV). To date, thousands of people have lost their lives annually due to HIV infection, and it continues to be a big public health issue globally. Since the discovery of the first drug, Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor (NRTI), to date, 30 drugs have been approved by the FDA, primarily targeting reverse transcriptase, integrase, and/or protease enzymes.

Synthetic azo-dye, Tartrazine induces neurodevelopmental toxicity via mitochondria-mediated apoptosis in zebrafish embryos.

Tartrazine (TZ), or E 102 or C Yellow, is a commonly used azo dye in the food and dyeing industries. Its excessive usage beyond permissible levels threatens human health and the aquatic environment. While previous studies have reported adverse effects such as mutagenicity, carcinogenicity, and reproductive toxicity.

Furan based synthetic chalcone derivative functions against gut inflammation and oxidative stress demonstrated in in-vivo zebrafish model.

Inflammatory Bowel Disease (IBD) is a group of persistent intestinal illnesses resulting from bowel inflammation unrelated to infection. The prevalence of IBD is rising in industrialized countries, increasing healthcare costs. Whether naturally occurring or synthetic, chalcones possess a broad range of biological properties, including anti-inflammatory, anti-microbial, and antioxidant effects.

Design, synthesis and anti-Tb evaluation of chalcone derivatives as novel inhibitors of InhA.

A series of halogenated chalcone derivatives were designed and developed for anti-tubercular activity. Novel molecules were designed and screening were performed using admetSAR, SwissADME, and Osiris Property Explorer. From the initial filter the top 10 compounds were docked using the Autodock tool 1.

Role and mechanistic actions of protein kinase inhibitors as an effective drug target for cancer and COVID.

Kinases can be grouped into 20 families which play a vital role as a regulator of neoplasia, metastasis, and cytokine suppression. Human genome sequencing has discovered more than 500 kinases. Mutations of the kinase itself or the pathway regulated by kinases leads to the progression of diseases such as Alzheimer's, viral infections, and cancers.

Deuterated driven new chemical entities: An optimistic way to improve therapeutic efficacy.

In organic chemistry, the use of deuterium exchange as a tool to study the mechanism of chemical reaction has been well explored. Since two decades, the research focus on deuterated bioactive molecules has been gaining attention for investigating the therapeutic potential of deuterium replacement in a chemical structure. Recently, Food Drug Administration (FDA) approved the first deuterium-labeled drug "deutetrabenazine", and notified the deuterated drugs as new chemical entities (NCEs).

An overview of mechanism and chemical inhibitors of shikimate kinase.

Tuberculosis is a highly infectious disease other than HIV/AIDS and it is one of the top ten causes of death worldwide. Resistance development in the bacteria occurs because of genetic alterations, and the molecular insights suggest that the accumulation of mutation in the individual drug target genes is the primary mechanism of multi-drug resistant tuberculosis. Chorismate is an essential structural fragment for the synthesis of aromatic amino acids and synthesized biochemically by a number of bacteria, including Mycobacterium tuberculosis, utilizing the shikimate pathway.

Docking studies and molecular dynamics simulation of triazole benzene sulfonamide derivatives with human carbonic anhydrase IX inhibition activity.

Carbonic anhydrase IX has been used as a hypoxia endogenous marker in a range of solid tumors including renal cell, lung, bladder and tumors of the head and neck. α-CA IX isozyme is over-expressive in hypoxic environment which becomes an attractive target for the design of inhibitors' targeting cancer particularly, tumor progression and invasion. In the process of designing new leads for the inhibition of tumor-associated hCA IX, the best triazole benzene sulfonamide derivatives were obtained from the QSAR model published in the research paper as cited.

An Overview of Spike Surface Glycoprotein in Severe Acute Respiratory Syndrome-Coronavirus.

The novel coronavirus originated in December 2019 in Hubei, China. This contagious disease named as COVID-19 resulted in a massive expansion within 6 months by spreading to more than 213 countries. Despite the availability of antiviral drugs for the treatment of various viral infections, it was concluded by the WHO that there is no medicine to treat novel CoV, SARS-CoV-2.

Identification of novel scaffold using ligand and structure based approach targeting shikimate kinase.

Tuberculosis (TB) remains a major global health problem. It causes ill-health among millions of people each year and rank as the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV). Shikimate kinase is one of the major enzymes targeted for TB.

Molecular insights into benzene sulphonamide substituted diarylpyrazoles as cyclooxygenase-2 inhibitor and its structural modifications.

Quantitative Structure Activity Relationship (QSAR) is one of the realistic and most successful methods for drug design in optimizing a lead. A series of forty-four molecules from diarylpyrazole benzene sulphonamide derivatives with their cyclooxygenase-2 inhibitory activity were subjected to qsar studies using QSARINS software. The significant two descriptor qsar model generated showed correlation coefficient of cross validation leave one out (Q)=0.