Current Issue : July-September Volume : 2025 Issue Number : 3 Articles : 5 Articles
Background: The study aims to evaluate the potential of trifluoromethyl thioxanthene derivatives across various biological activities, including antioxidant properties, anti-amylase effects, pancreatic lipase inhibition, anticancer activity, and COX inhibition. This research offers insights into the therapeutic applications of these compounds for managing metabolic disorders and inflammation. Method: Tertiary alcohols were synthesized using Grignard reagents and subsequently combined with L-cysteine, with their structures confirmed via NMR and IR spectroscopy. Results: The results indicated compound 3 exhibited the highest antioxidant potential, with 46.6% at 80 μg/mL in the DPPH assay. Compound 4 showed moderate pancreatic lipase inhibition, exhibiting an IC50 range of 100.6 to 277 μM. Compound 1 revealed potent anticancer activity against HeLa cells, with an IC50 of 87.8 nM. Compound 2 showed a potent antioxidant and anti-amylase activity with IC50 of 1.67 ± 0.5 and 60.2 ± 0.8 μM, respectively. Furthermore, the synthesized compounds 1, 3, and 4 displayed promising COX-2 inhibition with IC50 values ranging from 6.5 to 27.4 nM, suggesting potential anti-inflammatory benefits. Conclusions: This study highlights the significant biological activities of trifluoromethyl thioxanthene derivatives, positioning them as promising candidates for the treatment of cancer, metabolic disorders, and inflammation. These compounds demonstrated noteworthy antioxidant and enzyme inhibition properties, warranting further in vivo studies to confirm their therapeutic efficacy....
Background/Objectives: PARP inhibitors (PARPi) are pivotal to treating homologous recombination repair-deficient (HRD) cancers, particularly BRCA1/2-mutated ovarian and breast cancers. However, most ovarian and breast cancers harbor wild-type (WT) BRCA1/2, limiting PARPi eligibility. This study aims to identify an approved drug that could induce a BRCAness phenotype, thereby sensitizing WT BRCA cancers to PARPi. Methods: Ovarian and breast cancer cell lines with WT BRCA1/2 were treated with ivosidenib. HR repair efficiency was assessed via RAD51 foci formation and reporter assays. Synthetic lethality with PARPi was evaluated using viability and colony formation assays. Mechanistic studies included RNA-binding protein pulldown, co-immunoprecipitation, and functional analyses of DNA repair pathways. YTHDC2s role in HR was investigated through siRNA knockdown and rescue experiments. Results: Ivosidenib significantly reduced HR repair efficiency and sensitized cells to PARPi, inducing synthetic lethality. Mechanistically, ivosidenib directly bound YTHDC2, an m6A reader critical for HR. This interaction disrupted YTHDC2s ability to promote DNA double-strand break repair via HR, evidenced by impaired recruitment of repair proteins (e.g., BRCA1, RAD51) and accumulation of DNA damage (γH2AX foci). YTHDC2 knockdown phenocopied ivosidenib effects, while overexpression rescued HR defects. Conclusions: Ivosidenib induces BRCAness in WT BRCA ovarian and breast cancers by targeting YTHDC2, thereby suppressing HR repair and enhancing PARPi sensitivity. This uncovers a novel, metabolism-independent mechanism of ivosidenib, repositioning it as a therapeutic agent for HRD tumors. These findings propose a strategy to expand PARPi eligibility to WT BRCA cancers, addressing a critical unmet need in oncology....
Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyroneor pyridone-embedded analogs were designed and synthesized. Among the prepared analogs, the pyridone analog 19 bearing a methyl group at C-2 and a hydroxyl group at C-4 showed potent and selective growth inhibitory activity against human umbilical vein endothelial cells (HUVECs, IC50 = 0.001 μM, selective index over that against human epidermoid carcinoma KB3-1 cells = 6400), exceeding those of natural products. The analog 19 of oral administration exhibited excellent in vivo antitumor activity in mice subcutaneously inoculated with sarcoma S180 cells....
Background: The skin microbiota-derived metabolite butyrate plays a pivotal role in maintaining skin health. Unfortunately, unpleasant sensorial properties and unfavorable physicochemical properties strongly limit the butyrate use in dermatology clinical practice. This study investigates the effects of N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), a butyric acid releaser with neutral sensorial properties on skin keratinocyte function. Methods: Immortalized human keratinocyte cell line (HaCaT cells) was treated with FBA at various concentrations (0.001–1 mM) and time points (6–48 h). Cellular proliferation was assessed using MTT assays, while barrier integrity was evaluated by measuring tight junction proteins (occludin and ZO-1). Oxidative stress was analyzed using ROS assays and Western blot for Nrf2 and NF-κB expression. Markers of differentiation and extracellular matrix proteins were measured via quantitative PCR and wound-healing capability was assessed using a scratch assay. Results: FBA significantly enhanced keratinocyte proliferation at an optimal concentration of 0.1 mM. Tight junction protein expression increased, indicating improved barrier function. FBA reduced oxidative stress by upregulating Nrf2 and suppressing NF-κB activity. It also promoted the expression of differentiation markers (e.g., keratin-1, filaggrin) and extracellular matrix proteins (e.g., collagen type I and elastin). Furthermore, FBA accelerated wound closure, demonstrating its efficacy in enhancing the mechanisms of skin repair. Conclusions: Our results demonstrate that FBA enhances human keratinocyte cell differentiation, proliferation, and skin repair while protecting against oxidative stress. Its potential in cosmetics lies in delivering butyric acid benefits without organoleptic limitations, with possible applications in several skin condition characterized by deficient butyrate production and inflammation, such as atopic dermatitis....
Background: Spinal anesthesia is considered the method of choice for elective cesarean sections; however, it is not without maternal–fetal risks. Materials and Methods: This study compared the effects on maternal hemodynamics of intrathecal administration of fentanyl or morphine in parturients undergoing spinal anesthesia with 0.5% hyperbaric bupivacaine, with doses varied between 7.5 and 11 mg, depending on the patient’s height. Data from a cohort of 170 parturients were analyzed. The administered doses were intrathecal morphine at 0.1 mL (100 μg, solution of 1 mg/mL) or fentanyl at 0.25 mL (25 μg, solution of 50 μg/mL). This study included 80 patients in the fentanyl (F) group and 90 in the morphine (M) group. Results: Group F showed significantly higher post-intervention systolic blood pressure values than group M (95.30 ± 12.99 mmHg vs. 90.58 ± 14.75 mmHg, p = 0.032). The incidence of vomiting was significantly less frequent in group F compared to group M (1, 1.3% vs. 10, 11.1%, p = 0.011). The total dose of ephedrine required for hypotension correction was significantly lower in the F group (12.75 ± 13.26 mg vs. 17.72 ± 16.73 mg, p = 0.035). Conclusions: The addition of fentanyl as an adjuvant alongside the local anesthetic in cesarean section is associated with enhanced hemodynamic stability compared to morphine, requiring lower doses of ephedrine and contributing to increased patient safety during elective cesarean surgery....
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