Spinosyn A derivatives as ASS1 activators and tumor inhibitors.

Insights into the cytotoxicity of Ganoderma adspersum mycelium extracts against human renal cancer cell lines

Rational design, synthesis and effective mechanism of sophoridine and matrine contains 2,3,4-triphenylpyridine derivatives as TopoⅠ inhibitors for the treatment of gastric carcinoma.

Strategic engineering of imidazopyridine-benzoxazole hybrids targeting microtubule dynamics: comprehensive inhibition of the metastatic cascade.

Nature-inspired chalcone-functionalized paracetamol derivatives as potential anticancer leads: synthesis, biological evaluation, apoptotic mechanisms, and in silico docking studies.

Current landscape and therapeutic prospects of indole-azole hybrids for colorectal cancer treatment: A mini-review.

Alphainterferons are cytokines that became famous in the treatment of certain infections and tumors due to their antiviral, antiproliferative, and immunomodulatory activities. While the production of these small proteins in Escherichia coli is well established, high-level overexpression typically results in the formation of insoluble and inactive inclusion bodies that need to be processed through costly and lengthy steps. Here we describe an optimized, inducer-free expression system using E. coli BL21 (DE3) and a pET-based vector with the human IFN-α2a gene. By strategically transitioning the culture from high-temperature biomass accumulation (37°C) to mild conditions (16°C) during the early-midlog phase, we leveraged basal expression to favor folding over aggregation. This approach achieved a cytoplasmic solubility of up to 75%. The protein was recovered using a streamlined one- or two-step ion-exchange chromatography protocol, resulting in maximum purified yields of 23.5mg/L. Characterization tests confirmed the protein's identity, high purity, in vitro activity, and correct disulfide bonding pattern. This method provides a cost-effective alternative for the production of soluble alphainterferon by eliminating the need for chemical inducers and complex refolding processes.

Cytotoxic and oxidative stress-related effects of N2O2-type Ni(II)-thiosemicarbazone complexes: Experimental and computational studies.

Identification of a novel chalcone derivative as ferroptosis inducer through targeting TrxR in prostate cancer.

Optimization of Azaspirooxindolinone-based PROTACs targeting BTK: Synthesis, kinase profiling, and degradation analysis

Tubulin is a validated anticancer target, yet the clinical translation of colchicine-binding site inhibitors remains limited by toxicity and resistance. To accelerate the discovery of safer tubulin-targeting agents, we employed a machine learning (ML)-driven drug repurposing strategy integrating computational and experimental validation. Robust AutoQSAR classification models were trained on 279 curated tubulin inhibitors and used to screen 4500 US FDA-approved drugs, predicting 1800 compounds as potential tubulin inhibitors. These candidates were subjected to multistage structure-based virtual screening using Glide HTVS, SP, and XP docking, narrowing the selection from 698 (HTVS) and 350 (SP) to 38 compounds at the XP stage. Binding free-energy calculations (MM-GBSA) and 200ns molecular dynamics simulations identified four stable colchicine-site binders: omeprazole, podofilox, sulfadoxine, and trimethoprim, exhibiting favourable binding energetics (Glide XP scores -10.06 to -8.12kcal/mol; ΔG bind ranging from -10.06 to -8.12kcal/mol; ΔG bind ranging from -64.16 to -38.61kcal/mol). Biochemical tubulin polymerization assays confirmed tubulin inhibition, while cell-based cytotoxicity studies demonstrated low-micromolar antiproliferative activity of omeprazole and podofilox against melanoma (IC₅₀=4.32±0.29μM and 4.98±0.37μM, respectively) and colorectal cancer cells (IC₅₀=6.22±0.22μM and 5.76±0.18μM; n=3). Overall, this study highlights a ML-guided drug repurposing framework that, unlike prior colchicine binding site-focused virtual screening studies, integrates large-scale ML prioritization with experimental validation to identify novel colchicine-site-targeted anticancer candidates.

Discovery of mangiferin lipophilic amide derivatives as novel fatty acid synthase inhibitors with potent anti-hepatocellular carcinoma activity.

Iridal-type triterpenoids and stilbenes with anti-inflammatory activities from the rhizomes of Iris domestica.

Rational design of 2-substituted thio-7-chloroquinazolin-4(3H)-one derivatives as dual EGFR/VEGFR-2 inhibitors with broad-Spectrum anticancer and apoptotic activities.

Discovery of novel olaparib-β-carboline hybrids for treating BRCA-deficient triple negative breast cancer.

Targeting ROR1 with humanized antibody drug conjugates and cytokine fusion proteins for cancer therapy.

Antiproliferative Activity and Acute Toxicity of α,β-Bis(diphenylphosphine Oxide)ethanes Obtained by Bisphosphorylation of Acetylenes: Electrosynthesis Under Mild Conditions Versus Improved Superbasic Medium Synthesis.

Design, Synthesis, and Biological Evaluation of Indolin-2-One-Matrine Derivatives as Potential VEGFR-2-Targeting Agents for Hepatocellular Carcinoma.

Evaluation of Active and Passive Targeting Drug Delivery Systems as a Mechanism to Improve the Anticancer Potential of Titanium(IV).

Papillary thyroid carcinoma (PTC) is primarily managed through surgical intervention, underscoring the importance of understanding the biological effects of anesthetic agents used during such procedures. Dexmedetomidine is a widely used clinical anesthetic; however, its direct effects on PTC cells and the underlying mechanisms remain unclear. This study combined bioinformatic analysis and in vitro experiments to investigate these mechanisms. We identified 25 potential dexmedetomidine targets in PTC through database screening and further identified 10 hub genes. GO and KEGG enrichment analyses indicated that these genes were significantly involved in the MAPK signaling pathway, among others. In vitro experiments showed that dexmedetomidine, at micromolar concentrations, inhibited cell proliferation and migration, induced apoptosis, and caused G2/M phase arrest in a concentration-dependent manner. Mechanistic investigations revealed that dexmedetomidine concurrently activated the p38 MAPK pathway and suppressed PI3K/Akt signaling. Rescue experiments confirmed that inhibition of p38 reduced its pro-apoptotic effect, whereas activation of Akt reversed its anti-proliferative activity. These findings demonstrate, in an in vitro model, that dexmedetomidine suppresses malignant behaviors in PTC cells through synergistic regulation of the p38 MAPK and PI3K/Akt signaling pathways, providing novel mechanistic insights into its pleiotropic effects. Nevertheless, translating these in vitro findings into clinical practice warrants further investigation.