Anti-cancer agents in medicinal chemistry最新文献

Background: Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear.

Objective: This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma.

Methods: Here, a variety of in vitro and in vivo experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS.

Results: The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOSinduced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, in vivo experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy.

Conclusion: These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway.

Background: This study aims to enhance the delivery of polyphenols using nanotechnology.

Objective: To develop and evaluate liposomal formulations for improved delivery and stability of polyphenols, specifically focusing on Rutin.

Methods: Liposomal formulations were meticulously prepared via the Thin-Film Hydration method. Comprehensive physical characterization was conducted, including stability assessments using Dynamic Light Scattering (DLS) and Thermogravimetric Analysis (TGA). The free radical scavenging activity was measured using the DPPH• assay, and MTT cell viability assays were performed to assess cytotoxicity.

Results: The results demonstrated a significant reduction in nanoparticle size from 123 nm to 116 nm and an increase in charge from -14 to -22 with rising Rutin concentrations. The formulation achieved enhanced homogeneity at a Rutin concentration of 2.0 mg/mL and showed higher stability. Incorporating Rutin improved the formulation's stability over 30 days, as evidenced by a decrease in the Differential Scanning Calorimetry peak temperature from 58.65 °C to 54.42 °C. Rutin-loaded and co-loaded nanoliposomes exhibited remarkable selectivity against PANK1 and MCF7 cell lines, with IC50 values of 2.13±0.35 μg/mL and 4.75±0.19 μg/mL, respectively.

Conclusion: PEGylated Rutin-loaded nanoliposomes offer a promising platform for biodegradable and biocompatible drug delivery systems, enhancing the bioavailability, solubility, and stability of the polyphenols.

Objective: This study utilized three cell lines: normal prostate epithelial RWPE-1, androgen-dependent LNCaP, and androgen-independent PC3. We investigated the inhibitory effects of phenylboronic acid (PBA)'s inhibitory effect on cellular proliferation due to its ability to disrupt microtubule formation in prostate cancer cell lines. Additionally, this study aimed to assess the cytotoxic effects of PBA on prostate cancer cells using twodimensional (2D) and three-dimensional (3D) cell culture models.

Methods: The IC50 values of PBA and colchicine were determined through viability assays in 2D and 3D models. Colony formation, proliferation, and migration assays were conducted. Immunofluorescence intensity analysis of MAPKKK proteins (ERK, JNK, p38) was performed to explore the mechanism of cellular response to PBA.

Results: The IC50 values were determined for each treatment group. After 48-hour of PBA treatment, migration was inhibited more effectively than with colchicine in both cancer cell lines. After 24-hour, PBA reduced colony formation and proliferation. PBA treatment for 24-hour decreased JNK expression in PC3 and LNCaP cells in 2D models. Both PBA and colchicine increased p38 expression in PC3 spheroids. PBA's effects on cell deformation were visualized in semi-thin sections, marking the first ultrastructural observation of PBA-induced morphological defects in cancer cells.

Conclusion: PBA exerts antimitotic effects by inhibiting proliferation and migration and triggers diverse metabolic responses across different cell lines. Furthermore the low toxicity of PBA's low toxicity on RWPE-1 cells suggests its potential as a promising chemotherapeutic agent for future studies.

Background: Xanthene derivatives are a notable class of heterocyclic compounds widely studied for their significant biological impact. These molecules, found in both natural and synthetic forms, have attracted substantial scientific interest due to their broad spectrum of biological activities. The xanthene nucleus, in particular, is associated with a range of potential pharmaceutical properties, including antibacterial, antiviral, antiinflammatory, anticancer, and antioxidant effects. Their structural flexibility allows for modifications that can enhance specific biological functions, making them valuable candidates in medicinal chemistry and drug development.

Objective: Multi-component reactions involving two equivalents of 5,5-dimethylcyclohexane-1,3-dione with aromatic aldehydes yield xanthene derivatives that are known for their biological activity. Additionally, fused xanthene derivatives are formed through subsequent heterocyclization reactions, resulting in compounds with a broad range of biological properties.

Methods: Various xanthene derivatives incorporating thiophene and thiazole moieties were synthesized. Compounds 3a-c were further subjected to heterocyclization reactions to produce fused xanthene derivatives with additional heterocyclic components, enhancing their biological activity. The cytotoxic effects of the synthesized compounds were assessed across six cancer cell lines. Inhibition studies on c-Met kinase and the PC-3 cell line were conducted.

Result: Additionally, the compounds' inhibitory activity against tyrosine kinases was evaluated, and morphological changes in the A549 cell line were observed with the two most potent compounds.

Conclusion: The synthesized heterocyclic compounds, derived from 5,5-dimethylcyclohexane-1,3-dione and related cyclohexanone derivatives, exhibited significant inhibitory effects across various cancer cell lines. Specifically, compounds 3b, 5c, 5d, 7b, 7c, 7d, 9a, 9b, 10b, 10c, 12c, 15b, 15c, 16b, 16c, 17c, 17d, 17e, and 17f demonstrated high levels of inhibition, indicating potential for further exploration of xanthene-based heterocyclic compounds to enhance anticancer properties.

Background: Anlotinib has demonstrated durable clinical benefits in patients with unresectable or metastatic bone and soft-tissue sarcomas.

Methods: 92 patients treated with chemotherapy combined with or without anlotinib were collected and analyzed. The objective response rate (ORR) and disease control rate (DCR) were analyzed. Long-term survival was assessed using the Kaplan-Meier method, including median progression-free survival (mPFS) and overall survival (mOS).

Results: Liposarcoma, synovial sarcoma, and rhabdomyosarcoma were the primary pathological subtypes of the 92 patients. The median age was 46 (range, 11-75) years. The ORR and DCR of the anlotinib-chemotherapy combination used as first-line therapy were 31.9% and 85.1%, respectively. However, the ORR and DCR were only 6.7% and 57.8% in the chemotherapy alone, respectively. Compared with the chemotherapy group, improvements were observed in the mPFS and mOS with anlotinib-based regimen (mPFS, 8.3 vs. 3.0 months; mOS, 59.0 vs. 22.0 months). Anlotinib-associated adverse events were well tolerated and mainly occurred in grades I and II. New anlotinib-related adverse reactions were not noted.

Conclusion: Anlotinib-based regimen as a first-line therapy showed a positive effect on the treatment of unresectable or metastatic BSTSs. The anlotinib-associated adverse events were minor and well tolerated.

Background: Irisquinone, an important compound extracted from Semen Irisis, has been used clinically as a radiotherapy sensitizer for lung, oesophageal, head and neck, breast and leukemia cancers. However, the mechanism by which it acts against cancer is still unclear.

Objective: The present study aims to investigate the anti-tumor activity and mechanism of Irisquinone.

Methods: The effect of Irisquinone on cell viability and proliferation was evaluated using the CCK-8 assay. Fluorescence probe (Fast-TRFS) and DTNB assay were used to observe the inhibitory effect of Irisquinone on both intracellular and extracellular thioredoxin reductase (TrxR). The level of reactive oxygen species (ROS) in tumour cells was assessed using the DCFH-DA probe. Annexin V-FITC/PI, staining and microscopy experiments, were used to examine the apoptosis and pyroptosis. Western blotting analyses confirmed that Irisquinone induced apoptosis and pyroptosis in cancer cells by inhibiting TrxR to increase ROS generation.

Results: Our research has shown that Irisquinone has anti-proliferative effects on several cancer cell lines while having low toxicity to normal cells. The amount of ROS induced by inhibition of TrxR activated the BAX (proapoptotic protein) and caspase-1(the pro-pyroptotic protein) to induce apoptosis and pyroptosis.

Conclusion: Irisquinone showed anticancer activity through inhibiting TrxR. These results suggested that Irisquinone will be developed to be an anti-tumor drug possibility.

Introduction/objective: Plants and their bioactive compounds play a crucial role in the pharmaceutical industry for treating cancer. To date, the cytotoxic and antiproliferative effects of Hypericum perforatum methanol extract on human thyroid cancer cell lines have not been thoroughly explored. The present study aimed to assess the potential anti-cancer effects of HPME on human thyroid cancer and investigate its potential therapeutic benefits.

Methods: HPME was prepared using the maceration method, and its antioxidant activity was examined. Cytotoxicity studies were then carried out, followed by an investigation of the possible effects of HPME on metastasis and colony-forming capacities of human thyroid cancer cells. Afterward, qRT-PCR, western blotting, and apoptosis assays were performed.

Results: Cytotoxicity studies revealed notable cytotoxicity of HPME against the TT cell line. Moreover, HPME significantly curtailed metastasis and invasion of TT cells in an in vitro wound healing assay. Analyses of gene expressions demonstrated an elevation in caspase-12, caspase-3, and Bax, coupled with a reduction in BcL-2, APOE, and CLU expression. Following HPME treatment, there was an increase in the protein expression levels of Bax and Caspase-12, while a decrease in the BcL-2, APOE, and CLU protein expression. Furthermore, apoptotic studies indicated an increase in early apoptosis.

Conclusion: Overall results revealed that HPME demonstrates a notable antioxidant capacity in human thyroid cancer. It exerts an influence on crucial biological processes associated with cancer, indicating its potential to hinder the proliferation of human thyroid cancer cells by enhancing apoptosis through the upregulation of gene and protein expression, particularly involving caspases.

Mesenchymal‒epithelial transition factor (c-Met), a receptortyrosine kinase (RTK), plays a vital role in cell proliferation, migration and invasion, and tumour metastasis.

Objective: With increasing duration of treatment, many tumours gradually develop drug resistance. Therefore, novel antitumour drugs need to be developed to treat patients with tumours. Targeting c-met inhibitors may be an effective treatment strategy.

Methods: Scientific databases such as ScienceDirect, PubMed, the Wiley Online Library, and Social Sciences Citation Index were used to collect information. All the relevant literature was reviewed, and the available literature was screened. The upstream and downstream pathways of c-Met and their relevance to antitumour effects were searched based on the articles' title, abstract, and full text. The c-Met-targeting drugs with antitumour effects are summarized below. A "citation within a citation" or snowballing approach was used in this screening process to identify additional papers that may have been missed in the initial literature screening process. High-quality studies published in peer-reviewed journals were summarized and prioritized for citation in the review.

Results: In recent years, research on small-molecule targeted drugs has developed rapidly. Many results have also been achieved in the synthesis and isolation of c-Met inhibitors from natural compounds and traditional Chinese medicines.

Conclusion: This article summarizes the developments in anti-c-Met drugs, which are synthesized and isolated from natural compounds and traditional Chinese medicine (TCM). This study provides primary resources for the development of c-Met inhibitors.

Objective: Lung cancer is the primary cause of cancer-related deaths globally. Protein kinase B (AKT) protein is associated with many pathways in non-small cell lung cancer (NSCLC), such as proliferation, migration, invasion, and apoptosis. Mushrooms have a long history of being used in traditional medicine to treat various diseases. Scientists have been exploring the potential of mushrooms for their antioxidant and anticancer properties. In our study, the anti-oxidant, invasion, and apoptosis effects of mushroom extracts were investigated in NSCLC.

Materials and methods: Non-Small Cell Lung Cancer cell lines H1299, PC-3, and PC-14 were used in our study. After obtaining the extracts of Rhizopogon luteolus and Ganoderma adspersum, IC50 value was calculated as 25.04-11.73-16.54 ng/ul for R. luteolus and 2.97-1.53-1.01ug/ul for G. adspersum, respectively, in H1299, PC3 and PC14 cell lines. Afterward, proliferative and invasion effects, as well as apoptosis and anti-oxidant effects, were investigated using the IC50 dose. Western blotting was performed to investigate the pathways of these effects.

Results: According to the results of our study, Rhizopogon luteolus and Ganoderma adspersum extracts have anti-proliferative and anti-invasive effects on non-small lung cancer cell lines and induced apoptosis, which has been found to increase the anti-oxidant effect. It was found that this effect was due to cross-talk between antioxidant activity and the AKT-Rb pathway.

Conclusion: We anticipate that Rhizopogon luteolus and Ganoderma adspersum extracts will be effective in cancer treatment by suppressing lung cancer cells via p-Akt and Rb.