Synthesis, biological evaluation, and studies of lantadene-derived pentacyclic triterpenoids as anticancer agents targeting IKK-β.

We report the anticancer activity, structure-activity relationships (SAR), molecular mechanism, and docking studies of nine pentacyclic triterpenoids derived from lantadene A. The NCI-60 cytotoxicity screening of synthesized compounds on 60 human tumor cell lines, representing nine different cancers revealed that compound , bearing dual C-3 and C-22 butyryloxy substitutions at the pentacyclic triterpenoid scaffold, displays remarkable potency with mean growth inhibition of 98.7% at 10 μM.

Pyrazoles as Anti-inflammatory and Analgesic Agents: and Studies.

Background: Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities.

MK591 (Quiflapon), a 5-lipoxygenase inhibitor, kills pancreatic cancer cells via downregulation of protein kinase C-epsilon.

Introduction: Pancreatic tumors and cell lines derived from them exhibit elevated expression of 5-lipoxygenase (5-Lox), whereas non-tumor glands or normal cells do not exhibit this overexpression. Arachidonic acid stimulates pancreatic cancer cell growth via metabolic conversion through the 5-Lox pathway, and inhibition of 5-Lox activity decreases the viability of pancreatic cancer cells. However, the downstream signaling mechanisms through which 5-Lox exerts its effects on the survival of pancreatic cancer cells remain to be elucidated.

Unlocking the Pharmacological Potential of Benzimidazole Derivatives: A Pathway to Drug Development.

Heterocyclic molecules have fascinated a massive interest in medicinal chemistry. They are heterocyclic compounds that have gained significance due to their diverse variety of pharmacological activities. Benzimidazole is a heterocyclic compound consisting of benzene and imidazole rings.

Unveiling mortality risk factors in paediatric sickle cell disease patients during acute crises in the Democratic Republic of the Congo.

Sickle cell disease (SCD) is a significant health burden in the Democratic Republic of the Congo (DRC). This study aims to identify predictive factors of mortality in SCD children admitted to emergency care in Lubumbashi, DRC. We performed a non-interventional cohort follow-up on SCD patients aged 0 to 16 admitted for a "true emergency".

Prodrug Rewards in Medicinal Chemistry: An Advance and Challenges Approach for Drug Designing.

This article emphasizes the importance of prodrugs and their diverse spectrum of effects in the field of developing novel drugs for a variety of biological applications. Prodrugs are chemicals that are supplied inactively, but then go through enzymatic and chemical transformation in vivo to release the active parent medication that can have the desired pharmacological effect. By adding an inactive chemical moiety, prodrugs are improved in a number of ways that contribute to their potency and durability.

Daclatasvir, an Antiviral Drug, Downregulates Tribbles 2 Pseudokinase and Resensitizes Enzalutamide-Resistant Prostate Cancer Cells.

FDA-approved enzalutamide is commonly prescribed to reduce the growth of advanced prostate cancer by blocking androgen receptor function. However, enzalutamide-resistant prostate cancer (ERPC) invariably develops and progresses to metastatic, lethal disease. Management of ERPC poses a special problem not only because available therapeutic regimens cannot effectively kill ERPC cells but also due to their propensity to invade large bones.

(+)-Cyanidan-3-ol inhibits epidermoid squamous cell carcinoma growth via inhibiting AKT/mTOR signaling through modulating CIP2A-PP2A axis.

Background: Despite recent advances in the treatment of squamous cell skin cancer (SCSC), the disease persists, and treatment resistance develops. Thus, identifying new targets and developing new therapeutic approaches showing low vulnerability to drug resistance is highly needed.

Purpose: This study aimed to reveal a novel targeted phytotherapeutic strategy for SCSC treatment alone or in combination with standard targeted anticancer molecules.

Pyrazole based Furanone Hybrids as Novel Antimalarial: A Combined Experimental, Pharmacological and Computational Study.

Background: Malaria parasite strains are resistant to the therapeutic effect of prophylactics medicines presently available. This resistance now poses a significant challenge to researchers to beat malaria parasitic infections. Strategies such as investigating newer hybrid chemical entities and specified drug targets may help us spot new efficient derivatives that bind to the parasites in a more specific manner and inhibit their growth.

Tribbles 2 pseudokinase confers enzalutamide resistance in prostate cancer by promoting lineage plasticity.

Enzalutamide, a second-generation antiandrogen, is commonly prescribed for the therapy of advanced prostate cancer, but enzalutamide-resistant, lethal, or incurable disease invariably develops. To understand the molecular mechanism(s) behind enzalutamide resistance, here, we comprehensively analyzed a range of prostate tumors and clinically relevant models by gene expression array, immunohistochemistry, and Western blot, which revealed that enzalutamide-resistant prostate cancer cells and tumors overexpress the pseudokinase, Tribbles 2 (TRIB2). Inhibition of TRIB2 decreases the viability of enzalutamide-resistant prostate cancer cells, suggesting a critical role of TRIB2 in these cells.

Bioinformatic Analyses of Canonical Pathways of TSPOAP1 and its Roles in Human Diseases.

TSPO-associated protein 1 (TSPOAP1) is a cytoplasmic protein and is closely associated with its mitochondrial transmembrane protein partner translocator protein (TSPO). To decipher the canonical signalling pathways of TSPOAP1, its role in human diseases and disorders, and relationship with TSPO; expression analyses of TSPOAP1- and TSPO-associated human genes were performed by Qiagen Ingenuity Pathway Analysis (IPA). In the expression analysis, necroptosis and sirtuin signalling pathways, mitochondrial dysfunction, and inflammasome were the top canonical pathways for both TSPOAP1 and TSPO, confirming the close relationship between these two proteins.

Isolation optimisation, synthesis, molecular docking and ADMET studies of lantadene a and its derivatives.

A simple and economical method was developed for the extraction and isolation of pentacyclic triterpenoid lantadene A from the leaves of . The lantadene A displays significant anti-inflammatory and anticancer properties via the inhibition of IKK-mediated NF-κB protein. Therefore, the derivatives of lantadene A were synthesised to further optimise the pharmacophore for anti-inflammatory and anticancer activities.

Pharmacological and genetic targeting of 5-lipoxygenase interrupts c-Myc oncogenic signaling and kills enzalutamide-resistant prostate cancer cells via apoptosis.

Much of the morbidity and mortality due to prostate cancer happen because of castration-resistant prostate cancer (CRPC) which invariably develops after anti-androgenic therapy. FDA-approved enzalutamide is commonly prescribed for CRPC which works by blocking androgen receptor function. However, even after initial good response, enzalutamide-resistant prostate cancer (ERPC) develops which eventually leads to widespread metastasis.

Resolving Perplexity: Comparison of Endoscopic Dacryocystorhinostomy With and Without Stent.

Endoscopic dacryocystorhinostomy (DCR) is an effective surgical procedure to treat nasolacrimal duct obstruction. This study was conducted with an aim of comparing the success rate between use of stent and without use of stent in endoscopic DCR. A prospective randomized study was conducted.

Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations.

Based on their lobule location, hepatocytes display differential gene expression, including pericentral hepatocytes that surround the central vein, which are marked by Wnt-β-catenin signaling. Activating β-catenin mutations occur in a variety of liver tumors, including hepatocellular carcinoma (HCC), but no specific therapies are available to treat these tumor subsets. Here, we identify a positive relationship between β-catenin activation, its transcriptional target glutamine synthetase (GS), and p-mTOR-S2448, an indicator of mTORC1 activation.

HDAC1 Governs Iron Homeostasis Independent of Histone Deacetylation in Iron-Overload Murine Models.

Aims: Iron-overload disorders are common and could lead to significant morbidity and mortality worldwide. Due to limited treatment options, there is a great need to develop novel strategies to remove the excess body iron. To discover potential epigenetic modulator in hepcidin upregulation and subsequently decreasing iron burden, we performed an epigenetic screen.

MicroRNA-122 regulates polyploidization in the murine liver.

Unlabelled: A defining feature of the mammalian liver is polyploidy, a numerical change in the entire complement of chromosomes. The first step of polyploidization involves cell division with failed cytokinesis. Although polyploidy is common, affecting ∼90% of hepatocytes in mice and 50% in humans, the specialized role played by polyploid cells in liver homeostasis and disease remains poorly understood.

WNT5A inhibits hepatocyte proliferation and concludes β-catenin signaling in liver regeneration.

Activation of Wnt/β-catenin signaling during liver regeneration (LR) after partial hepatectomy (PH) is observed in several species. However, how this pathway is turned off when hepatocyte proliferation is no longer required is unknown. We assessed LR in liver-specific knockouts of Wntless (Wls-LKO), a protein required for Wnt secretion from a cell.

Genome Sequences of Mycobacteriophages AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo, New Members of Cluster B.

AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo are newly isolated phages of Mycobacterium smegmatis mc(2)155 discovered in Pittsburgh, Pennsylvania, USA. All five phages share nucleotide similarity with cluster B mycobacteriophages but span considerable diversity with Corofin and OrangeOswald in subcluster B3, AlanGrant and Vincenzo in subcluster B4, and Baee in subcluster B5.

In Vitro and In Vivo Evaluation of Small Cationic Abiotic Lipopeptides as Novel Antifungal Agents.

We investigated the antifungal potential of short lipopeptides against clinical fungal isolates with an objective to evaluate their clinical feasibility. All tested lipopeptides exhibit good antifungal activity with negligible difference between the MICs against susceptible and drug-resistant clinical fungal isolates. The MTT assay results revealed the lower cytotoxicity of lipopeptides toward mammalian cells (NRK-52E).

Topical (+)-catechin emulsified gel prevents DMBA/TPA-induced squamous cell carcinoma of the skin by modulating antioxidants and inflammatory biomarkers in BALB/c mice.

An emulsified gel of (+)-catechin was developed and evaluated topically against 7,12-dimethylbenz(a)anthracene-induced and 12-O-tetradecanoylphorbol-13-acetate-promoted (DMBA-induced and TPA-promoted) squamous cell carcinoma of the skin in BALB/c mice. The biological evaluation outcome indicated that the (+)-catechin emulsified gel increased the activity of oxidative stress biomarkers glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx), whereas it decreased the level of malondialdehyde (MDA). The mechanistic study showed that genes implicated in the inflammation and cancer, such as cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB), and inducible nitric-oxide synthase (iNOS), were down-regulated by (+)-catechin emulsified gel while inhibiting an inflammatory mediator prostaglandin E2 (PGE2).

In vitro and in vivo antibacterial evaluation and mechanistic study of ornithine based small cationic lipopeptides against antibiotic resistant clinical isolates.

We investigated the in vitro activities of short lipopeptides against a large panel of clinical isolates of antibiotic resistant bacteria. In the animal model, LP16 (5 mg/kg) significantly decreased the burden of viable colony forming unit (CFU) of bacteria. MTT assay results revealed the high selectivity of lipopeptides toward microbial cells.

Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.

The objective of this study was to evaluate the cytotoxicity of (+)-cyanidan-3-ol (CD-3) in human hepatocellular carcinoma cell line (HepG2) and chemopreventive potential against hepatocellular carcinoma (HCC) in Balb/c mice. The HepG2 cell line was treated with CD-3 at various concentrations and the proliferation of the HepG2 cells was measure by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB) and lactate dehydrogenase (LDH) assays. Cell apoptosis was detected by Hoechst 33258 (HO), Acridine orange/ethylene dibromide (AO/EB) staining, DNA fragmentation analysis and the apoptosis rate was detected by flow cytometry.

Cytotoxicity and apoptosis induction in human breast adenocarcinoma MCF-7 cells by (+)-cyanidan-3-ol.

The objective of this study was to evaluate the cytotoxicity and possible signalling pathway implicated in (+)-cyanidan-3-ol (CD-3) induced apoptosis in the human breast adenocarcinoma cell line (MCF-7). The effects of CD-3 on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB) and lactate dehydrogenase (LDH) assays. Cell apoptosis was detected by Hoechst 33258 (HO) and acridine orange/ethylene dibromide (AO/EB) staining and DNA fragmentation analysis.

Chemopreventive efficacy of (+)-catechin-rich aqueous extract of Acacia catechu Willd. Heartwood against 7,12-dimethylbenz[a]anthracene-induced hepatocarcinoma in Balb/c mice.

The objective of this study was to investigate the chemopreventive potential of (+)-catechin-rich extract of Acacia catechu heartwood (AQCE) against 7,12-dimethylbenz[a]anthracene (DMBA)-induced hepatocellular carcinoma in Balb/c mice. The levels of liver injury markers, tumor markers, and oxidative stress were measured in serum and liver tissues. Furthermore, the levels of transcription factors were measured by ELISA.