Acute Myeloid Leukemia (AML) is a complex hematologic malignancy characterized by the rapid proliferation of abnormal myeloid precursor cells. The FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase, plays a pivotal role in regulating cell survival, proliferation, and differentiation within the hematopoietic system. Mutations in FLT3, particularly internal tandem duplications (ITDs) and point mutations within the tyrosine kinase domain (TKD), are prevalent in AML and are associated with poor prognosis and increased risk of relapse. The development of targeted therapies has revolutionized the landscape of cancer treatment by focusing on the inhibition of kinase signalling. Small-molecule inhibitors designed to selectively target receptor tyrosine kinases, such as PLX3397, have shown promising results in preclinical studies and early phase clinical trials. PLX3397 exerts its inhibitory effects by targeting CSF1R and KIT, leading to the disruption of receptor tyrosine kinase signalling cascades, suppression of leukemic cell growth, and induction of apoptosis. This study emphasizes the significance of FLT3 as a receptor tyrosine kinase as a therapeutic target for PLX3397. After evaluating the usefulness of PLX3397 as an enzyme inhibitor using ADMET prediction, PLX3397 was prepared for molecular docking in the FLT3 crystal structure (PDB: 4XUF). A molecular dynamics simulation was performed on PLX3397 to evaluate its binding affinity and protein stability in a simulated physiological environment. In conclusion, targeting FLT3 as a receptor tyrosine kinase with PLX3397 represents a promising therapeutic strategy for improving outcomes in patients with FLT3-mutated AML. Further clinical investigations are warranted to validate the efficacy and safety of PLX3397 and to optimize treatment strategies for AML patients based on the FLT3 mutational status.

Acute myeloid leukemia (AML) is a complex blood cancer that primarily affects relapsing or refractory patients receiving conventional chemotherapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer properties with restricted clinical efficacy attributable to cyclooxygenase (COX)-induced toxicities. To address this issue, a group of benzylamide analogs of the classical NSAIDs (NSI-1–NSI-9) were developed and synthesized to mask the carboxylic acid moiety and minimize COX-induced adverse effects while maintaining anticancer activity. The cytotoxic effect of such substances has been demonstrated in some leukemia cell lines (HL-60, MV4-11, KG1a, and K562). NSI-5 exerted the highest anti-leukemic activity among these sulindac analogs, as determined at a sub-micromolar level in all cell lines studied, by IC50. This mechanistic data also demonstrated that NSI-5 induced apoptosis that was dose-dependent, especially in HL-60 cell lines, and increased the sub-G1 cell fraction. This apoptotic process was also accompanied by a significant decrease in mitochondrial membrane potential, which is characteristic of the induction of the intrinsic apoptotic process. Interestingly, NSI-5 decreased the intracellular reactive oxygen species (ROS) and the expression of most antioxidants (catalase and glutathione synthetase), as well as the redox balance. Gene characterization in vitro also suggested activation of apoptotic pathways, where expression of Bax, Bak1, and Caspase-3 increased, suggesting a potential p53-independent apoptotic pathway, in contrast to control for Bcl-2 expression. Collectively, these findings indicate that NSI-5 is a promising in vitro anti-leukemic lead compound, with activity associated with mitochondrial dysfunction and altered redox regulation. The observed effects are consistent with previously reported COX-independent activity of structurally related NSAID derivatives, and support further investigation of NSI-5 in preclinical models.

The First Australian Community is one of the ancient civilizations which has been dependent upon the available surrounding natural resources for their clothing, nutrition and healing of disease. Unfortunately, some of their traditional medicines and / or their practical applications are lost because of poor written documentation. Plants form parts of ancient remedies used by Aboriginal peoples to heal several ailments due to their therapeutic activities. One of these medicinal plants is Hibbertia scandens (Snake Vine), which has been used by Aboriginal Communities as a traditional medicine to treat sores and rashes due to antibacterial and antiseptic properties of this plant.

Nanoemulsions are promising nanotechnology-based delivery systems that may improve the stability, bioavailability, and cellular uptake of therapeutic agents. Silver nanoparticles (AgNPs) have been reported to exhibit high antibacterial and anticancer activities via several mechanisms, such as the generation of oxidative stress and disruption of cellular membrane integrity. Breast cancer (MCF−7) and ovarian cancer (SK-OV−3) represent two highly aggressive malignancies that pose major global health challenges. Brown algae oil is a natural marine-derived product with a number of bioactive compounds, including fatty acids, sterols, and antioxidants, responsible for its numerous biological activities. Oil extracted from the brown alga Turbinaria turbinata, using hexane as an organic solvent, was formulated with silver nitrate (AgNO₃) using a surfactant-stabilized spontaneous emulsification method to prepare a silver-loaded T. turbinata oil nanoemulsion (Ag-TTO-NE). The biological performance of the system was evaluated against human cancer cell lines, including MCF−7 (breast cancer) and SK-OV−3 (ovarian cancer), in addition to pathogenic bacterial strains, and for antioxidant activity. The results demonstrated that the silver-loaded oil nanoemulsion (Ag-TTO-NE) exhibited anticancer activities against MCF−7 (breast cancer) and SK-OV−3, with IC50 values of 105.86 and 72.45 µg/mL and a Selectivity Index of 2.34 and 3.41, respectively. The silver-loaded oil nanoemulsion (Ag-TTO-NE) possessed antioxidant and antimicrobial activities against Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC90274) and Salmonella typhi (ATCC 6539). These results indicate that T. turbinata-based silver nanoemulsions deserve further exploration as multifunctional marine-derived nanoformulations. In silico ADMET analysis projected moderate to high oral absorption for most of the discovered compounds and suggested favorable pharmacokinetic properties of the individual ingredients. ADMET analysis suggested that the major compounds discovered by GC–MS have good medication-like characteristics. These computational predictions are supplemental information and are not to be taken as the pharmacokinetic behavior of the nanoemulsion itself. Overall, the present results are based on in vitro biological assays together with exploratory computational studies and constitute preliminary evidence for the subsequent exploration of this marine-derived nanoformulation.