Anti-cancer agents in medicinal chemistry最新文献

Background: In current scenario breast cancer measured as one of the dangerous health issues. An effective therapeutic class of drug known as aromatase inhibitors (AIs) is dominant against estrogen receptorpositive breast cancer. However, there is an urgent need to create target-specific AIs with better anti-breast cancer profiles due to the increased toxicity and adverse effects related to currently existing anti-breast cancer drugs.

Objectives: In the present study, we have designed of 100 novel tiazole analogues as aromatase inhibitors their pharmacophoric features were explored.

Method: Molecular docking was applied to a series of 4-substituted-1, 2, 3-triazoles containing letrozole for their aromatase inhibitory effects. The aromatase inhibitory activity of the compound in a series varies in the range of (IC₅₀ = 0.008-31.26 μM). A hydrogen atom positioned at R1 of the triazole ring in compound (01) was responsible for the most potent compound (IC₅₀ = 0.008 μM) in the series of 28 compounds as compared to letrozole. The self-organizing molecular field study was used to assess the molecular characteristics and biological activities of the compounds. The four models were developed using PLS and MLR methods. The PLS method was good for statistical analysis. The letrozole scaffold-based 100 compounds were designed by selecting an effective pharmacophore responsible for aromatase inhibitory activity. The designed compound was placed on the previous model as a test set, and its IC₅₀ values were calculated.

Result: Hydrogen bonds were established between the potent molecule (01) and the essential residues Met 374 and Arg 115, which were responsible for the aromatase-inhibiting action. Cross-validated q2 (0.6349) & noncross- validated r2 (0.7163) were discovered in the statistical findings as having reliable predictive power. Among 100 designed compounds, seven compounds showed good aromatase inhibitory activities.

Conclusion: The additional final SOMFA model created for the interactions between the aromatase and the triazole inhibitors may be helpful for future modification and enhancement of the inhibitors of this crucial enzyme.

Background: Resveratrol's structural similarity to commercialized anti-breast cancer medications such as Tamoxifen underlines its potential as a promising option for developing successful anti-breast cancer drugs. However, the pharmacokinetic issues associated with resveratrol, such as its low bioavailability, have piqued the attention of researchers in developing novel derivatives.

Methods: A novel phytoalexin derivative, RsvD1, was successfully synthesized using resveratrol extracted from green grape peels as a precursor to investigate its anti-breast cancer efficacy on Estrogen receptor (ER) positive and negative breast cancer cells.

Results: The comparative analysis revealed that RsvD1 exhibited remarkable radical scavenging ability (IC₅₀ = 2.21 μg/mL), surpassing the control, Trolox (IC₅₀ = 6.3 μg/mL). Furthermore, RsvD1 demonstrated enhanced and selective antiproliferative activity against ER-positive MCF-7 cells (IC₅₀ = 20.09 μg/mL) compared to resveratrol, the parent molecule (IC₅₀ = 30.90 μg/mL). Further investigations unveiled that RsvD1 induced apoptosis and DNA damage in MCF-7 cells, leading to cell cycle arrest at the G₀/G₁ phase after 24 hours of incubation. RTqPCR gene expression analysis indicated that RsvD1 down-regulated the CAXII (ER-dependent) genes. In silico predictions demonstrated that RsvD1 possesses promising potential as a drug candidate due to its drug-like characteristics and favourable ADMET profile. Moreover, molecular docking studies provided insights into the theoretical binding mode between RsvD1 and ERα protein.

Conclusion: The study highlights the therapeutic potential of the synthesized resveratrol derivative, RsvD1, positioning it as a promising scaffold for developing novel analogues with improved therapeutic properties and selectivity, specifically targeting ER+ breast cancer cells. Moreover, the compound's non-cytotoxic yet antiproliferative properties, coupled with its capability to induce programmed cell death and cell cycle arrest, enhance its potential as a highly effective drug candidate. As a result, this paves a promising path for the development of innovative and selective inhibitors targeting ER+ breast cancer with enhanced efficacy.

Aims: The aim of this study is to isolate the Millettia pinnata (Karanj) leaf extract for pure compound with anticancer properties and to study the molecular target of the isolates in non-small cell lung cancer cell lines.

Background: In our earlier research Millettia pinnata leaf extract has demonstrated potential anticancer activities. Thus, in pursuit of the bioactive compounds, the most potential active extract from our previous study was purified. Furthermore, the anticancer properties of the isolated compound karanjin was studied and aimed for apoptosis and restraining growth.

Methods: A novel method was developed through column chromatography for isolation and purification of the compound karanjin from leaf chloroform extract. The purified component was then characterised using FTIR, mass spectrometry, and NMR. An MTT-based cytotoxicity assay was used to analyse cell cytotoxicity, whereas fluorescence staining was used for apoptosis and reactive oxygen species inhibition quantification. Furthermore, the real-time PCR assay was used to determine the molecular mechanism of action in cells causing cytotoxicity induced by karanjin dosing.

Results: The anticancer activity of karanjin in A549 cell line exhibited prominent activity revealing IC50 value of 4.85 μM. Conferring the predicted molecular pathway study, karanjin restrains the proliferation of cancer cells through apoptosis, which is controlled by extrinsic pathway proteins FAS/FADD/Caspases 8/3/9. Downregulation of KRAS and dependent gene expression also stopped cell proliferation.

Conclusion: Karanjin has been identified as a compound with potential effect in non-small cell lung cancer cells. Molecular mechanism for apoptosis and inhibition of reactive oxygen species induced through H2O2 were observed, concluding karanjin have medicinal and antioxidant properties.

Background: Efficient targeted molecular therapeutics are needed for the treatment of triple-negative breast cancer (TNBC), a highly invasive and difficult-to-treat form of breast cancer associated with a poor prognosis.

Objectives: This study aims to evaluate the potential of selective CDK4/6 inhibitors as a therapeutic option for TNBC by impairing the cell cycle G1 phase through the inhibition of retinoblastoma protein (Rb) phosphorylation.

Methods: In this study, we synthesized a compound called JHD205, derived from the chemical structure of Abemaciclib, and examined its inhibitory effects on the malignant characteristics of TNBC cells.

Results: Our results demonstrated that JHD205 exhibited superior tumor growth inhibition compared to Abemaciclib in breast cancer xenograft chicken embryo models. Western blot analysis revealed that JHD205 could dosedependently degrade CDK4 and CDK6 while also causing abnormal changes in other proteins associated with CDK4/6, such as p-Rb, Rb, and E2F1. Moreover, JHD205 induced apoptosis and DNA damage and inhibited DNA repair by upregulating Caspase3 and p-H2AX protein levels.

Conclusion: Collectively, our findings suggest that JHD205 holds promise as a potential treatment for breast carcinoma.

The Prodiginins (PGs) natural pigments are secondary metabolites produced by a broad spectrum of gram-negative and gram-positive bacteria, notably by species within the Serratia and Streptomyces genera. These compounds exhibit diverse and potent biological activities, including anticancer, immunosuppressive, antimicrobial, antimalarial, and antiviral effects. Structurally, PGs share a common tripyrrolic core but possess variable side chains and undergo cyclization, resulting in structural diversity. Studies have investigated their antiproliferative effects on various cancer cell lines, with some PGs advancing to clinical trials for cancer treatment. This review aims to illuminate the molecular mechanisms underlying PG-induced apoptosis in cancer cells and explore the structure-activity relationships pertinent to their anticancer properties. Such insights may serve as a foundation for further research in anticancer drug development, potentially leading to the creation of novel, targeted therapies based on PGs or their derivatives.

Background: Breast cancer is the most commonly diagnosed cancer among women worldwide with limited treatment options. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is one of the main constituents of Brazilian propolis presenting different activities, including antitumoral effects against various types of cancer.

Objective: We evaluated the antitumoral potential and mechanisms of action of artepillin C against two distinct human breast cancer cell lines, MCF-7 and MDA-MB-231, to explore a new therapeutic candidate.

Methods: Cell viability was assessed by MTT assay and the long-term cytotoxicity was performed by clonogenic assay. The morphological changes were observed by light microscopy, analysis of cell death pathway by Annexin V FITC/propidium iodide (PI), lactate dehydrogenase (LDH) by colorimetry, DNA fragmentation by agarose gel and senescence by β-galactosidase. Detection of total reactive oxygen species (ROS) by fluorescence microscopy and determination of mitochondrial transmembrane potential by flow cytometry were also performed.

Results: Artepillin C presented a strong and dose-time-dependent cytotoxic effect on MCF-7 and MDA-MB-231 cell lines, with cytotoxicity more evident in MCF-7. In both cancer cell lines, the clonogenic potential was significantly reduced and the morphology of the cells was changed. The treatment also induced death by necrosis and late apoptosis in MCF-7 and MDA-MB-231 and induced cell senescence in MCF-7. Also, artepillin C increased total ROS in both cancer cells and decreased mitochondrial membrane potential in MDA-MB-231 cells.

Conclusion: Artepillin C presented antitumoral potential in two human breast cancer cell lines, MCF-7, and MDA-MB-231, suggesting a new promising option for the treatment and/or chemopreventive strategy for breast cancer.

The National Cancer Center published a comparative report on cancer data between China and the United States in the Chinese Medical Journal, which shows that colorectal cancer (CRC) ranks second in China and fourth in the United States. It is worth noting that since 2000, the case fatality rate of CRC in China has skyrocketed, while the United States has gradually declined. Finding tumor markers with high sensitivity and specificity is our primary goal to reduce the case fatality rate of CRC. Studies have shown that CRD-BP (Insulin-like growth factor 2 mRNA-binding protein 1) can affect a variety of signaling pathways, such as Wnt.nuclear factor KB (NF-κB), and Hedgehog, and has good biological effects as a therapeutic target for CRC. CRD-BP is expected to become a tumor marker with high sensitivity and specificity of CRC. This paper reviews the research on CRD-BP as a tumor marker of CRC.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that aid in extracellular matrix (ECM) remodeling. MMPs destroy the extracellular matrix, causing tumor growth and metastasis. MMPs are involved in the spread and metastasis of oral cancer. High levels of MMPs and oral squamous cell carcinoma have been linked to cancer prognosis. Modern medicine aims to prevent the illness from spreading through early intervention and examining changes in MMP genes. MMP gene polymorphism has recently been identified as one of the factors predicting susceptibility or risk in the development of oral carcinoma. This review aims to provide insight into the function of MMP subtypes involved in cancer. The genetic polymorphism in MMP genes and its predictive value in risk evaluation have been elaborated. Novel personalized therapeutic approaches for oral cancer, like the use of MMP inhibitors, nanoparticle-mediated targeting of MMP, or gene silencing by microRNA, can be designed.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-κB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.

Current cancer treatment options have presented numerous challenges in terms of reaching high efficacy. As a result, an immediate step must be taken to create novel therapies that can achieve more than satisfying outcomes in the fight against tumors. Ferroptosis, an emerging form of regulated cell death (RCD) that is reliant on iron and reactive oxygen species, has garnered significant attention in the field of cancer therapy. Ferroptosis has been reported to be induced by a variety of small molecule compounds known as ferroptosis inducers (FINs), as well as several licensed chemotherapy medicines. These compounds' low solubility, systemic toxicity, and limited capacity to target tumors are some of the significant limitations that have hindered their clinical effectiveness. A novel cancer therapy paradigm has been created by the hypothesis that ferroptosis induced by nanoparticles has superior preclinical properties to that induced by small drugs and can overcome apoptosis resistance. Knowing the different ideas behind the preparation of nanomaterials that target ferroptosis can be very helpful in generating new ideas. Simultaneously, more improvement in nanomaterial design is needed to make them appropriate for therapeutic treatment. This paper first discusses the fundamentals of nanomedicine-based ferroptosis to highlight the potential and characteristics of ferroptosis in the context of cancer treatment. The latest study on nanomedicine applications for ferroptosis-based anticancer therapy is then highlighted.