Anti-cancer agents in medicinal chemistry最新文献

Introduction: Statins are a class of cholesterol-lowering agents widely used in clinical practice to reduce plasma levels of low-density lipoprotein cholesterol in hyperlipidemic patients. Beyond their lipidlowering roles, statins exhibit several additional effects.

Methods: In the current review, we searched PubMed, ScienceDirect, and Google Scholar databases using the keywords "Statins," "HMG-CoA reductase inhibitors," "Anti-inflammatory," "Antioxidant," and "Anticancer" to provide an overview of the effects of statins. Articles published on these topics between 1990 and 2025 were included. The retrieved records were imported into EndNote, and duplicates were removed.

Result: Multiple potential therapeutic benefits of statins have been described, including suppression of apoptosis, antioxidant, anti-inflammatory and anticancer effects, immunomodulation and neuroprotection.

Discussion: NADPH oxidases (NOX) play a crucial role in the development of various diseases through excessive production of reactive oxygen species (ROS) and the creation of oxidative stress conditions. Stimulation of BDNF/Nrf2, inhibition of NOX pathways, and reduction of intracellular ROS via enhanced antioxidant activity represent possible mechanisms through which statins exert their effects. Interestingly, ROS and inflammatory cytokines activate nuclear factor kappa B (NF-κB), a critical factor in the development of malignant tumors, which induces the expression of genes involved in cell proliferation and carcinogenesis. Furthermore, statins inhibit NF-κB activity, a key transcriptional regulator in inflammatory responses.

Conclusion: Clinical evidence suggests that statins may reduce the risk of various cancers and disease recurrence due to their anti-inflammatory and antioxidant properties. These findings form the basis for new therapeutic avenues in cancer treatment, potentially offering a more promising strategy than statin monotherapy.

Introduction: Mentha spicata L. (Lamiaceae) has been used in traditional medicine to cure indigestion, stomach aches, and diarrhea. This research aims to synthesize silver nanoparticles from aqueous extract of M. spicata and to investigate its antioxidant, antibacterial, and anticancer activities.

Methods: The plant was extracted using maceration with water, and Mentha spicata-silver nanoparticles (MAgNPs) were prepared using a 5 mM silver nitrate solution. The antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide scavenging assays. Antibacterial analysis was done through the agar disk diffusion method. The anticancer potential was evaluated using the cytotoxicity and MTT assays.

Results: The phytochemical screening revealed the presence of flavonoids and other phenolic compounds. The aqueous extract and silver nanoparticles scavenged the DPPH and hydrogen peroxide free radicals, with IC50 values of 1.556 mg/mL and 1.695 mg/mL, respectively. The bacterial strains were susceptible to the extract and silver nanoparticles, with inhibitory zones ranging from 4 to 11 mm. The zeta analysis revealed a size of 70.08 nm and a potential of -13.17 mV. The XRD showed a crystalline structure of silver nanoparticles. The FTIR revealed a characteristic N-H stretching frequency. The extract and nanoparticles exhibited cytotoxic and anti-proliferative effects in vitro against MDA-MB-231 cancer cells, with a significant difference among means (p < 0.05).

Discussion: There is an urgent need to screen and standardize medicinal plants with medicinal benefits and less toxicity, which also serve as chelating agents in drug delivery.

Conclusion: The ability of the extract to scavenge free radicals and inhibit bacterial growth may be due to its chemical constituents. MAgNPs may be a viable option for potential application and development in cancer therapy.

Prostate-Specific Antigen (PSA) is a glycoprotein produced in the prostate and is widely used as a biomarker for the diagnosis of prostate cancer (PCa). Although elevated PSA levels are often associated with PCa, several noncancerous conditions can also lead to increased PSA. In addition to total PSA, various PSA isoforms are detectable in the blood of patients, and their levels may differ depending on the underlying pathophysiological condition, whether benign or malignant. Measuring serum PSA levels alone is not sufficient to detect PCa, leading to widespread overdiagnosis and overtreatment. Therefore, comprehensive biochemical insights into PSA and its isoforms, of normal, benign, and malignant origin, may improve PSA assays for PCa diagnosis. Apart from its role as a biomarker, PSA plays multiple roles in the pathophysiology of PCa by activating the Epithelial-Mesenchymal Transition (EMT) and promoting tumor progression, as well as regulating the invasion and metastasis of PCa cells. In PCa, elevated PSA levels are associated with immunosuppression, antiapoptotic properties, and inhibition of angiogenesis. A comprehensive review of numerous important research findings on PSA and its isoforms was conducted to elucidate the role of PSA as a biomarker and functional mediator in PCa pathophysiology. Thus, the use of PSA as a biomarker for the diagnosis of PCa can minimize unnecessary and inappropriate biopsies, identify suitable patients for prostate biopsy, ensure early diagnosis, and initiate treatment at an early stage of PCa. Furthermore, the role of PSA as a functional mediator will enable us to study the pathophysiology of patients with prostate cancer (PCa).

Introduction: Triple Negative Breast Cancer (TNBC), which makes up 15% of all breast cancers, is widely acknowledged as the most aggressive and challenging subtype of the disease. It is characterized by the absence of HER2 receptors, progesterone, and estrogen, which limits the options for targeted treatment and mainly affects younger women. It is associated with a poor prognosis due to its rapid progression, high recurrence rates, and risk of metastasizing into vital organs like the brain and lungs. These clinical challenges underscore the urgent need for personalized treatment plans and innovative therapeutic strategies.

Methods: Numerous studies have identified dysregulated signaling pathways in TNBC, including the PI3K/AKT/mTOR, JAK/STAT, Wnt/β-catenin, Notch, and MAPK/ERK pathways, which offer therapeutic targets.

Results: Recent developments in clinical and molecular research have presented potential treatment strategies. Pembrolizumab and other immune checkpoint inhibitors have demonstrated significant benefits when used in conjunction with chemotherapy for both early-stage and metastatic TNBC. In advanced patients, sacituzumab, govitecan, and other Antibody-Drug Conjugates (ADCs) have shown remarkable efficacy in delivering cytotoxic medications, improving progression-free survival. Significant obstacles still exist despite these developments, such as tumor heterogeneity and treatment resistance.

Discussion: This review highlights the beneficial effects of small molecule inhibitors and combination therapies in treating the deadliest type of breast cancer, as well as the therapeutic potential of targeting dysregulated signaling pathways and providing insight into potential avenues for developing new therapies.

Conclusion: To significantly enhance outcomes for TNBC patients, future research must concentrate on identifying predictive biomarkers and refining individualized therapy plans.

Introduction: Bone tumors, especially in advanced stages, pose serious diagnostic and therapeutic challenges due to their aggressive nature and the invasiveness of traditional biopsy techniques. Liquid biopsy offers a promising, minimally invasive alternative by analyzing tumor-derived components from bodily fluids, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs). These biomarkers enable dynamic and precise disease monitoring.

Objective: This review aimed to investigate the role of liquid biopsy in the diagnosis, prognosis, and treatment guidance of bone tumors, highlighting recent molecular advances and clinical findings.

Methods: A structured narrative review was conducted using PubMed, covering studies published up to July 2024. Studies involving osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma were included, focusing on the clinical implications of CTCs, ctDNA, and EVs from plasma, serum, and other fluids.

Results: Liquid biopsy technologies demonstrated high diagnostic accuracy in bone tumors. In osteosarcoma, CTC detection using qRT-PCR and FISH methods showed sensitivities up to 98.6% and was strongly associated with metastatic disease and recurrence risk. ctDNA profiling identified tumor-specific mutations, hypomethylation markers (e.g., IRX1), and early relapse indicators with up to 97.4% specificity. EV-associated biomarkers, particularly miRNAs, such as miR-25-3p and a 3-miRNA signature, distinguished tumor subtypes and predicted metastasis-free survival. Advanced techniques, like SERS and MALDI-TOF MS profiling of exosomes, achieved diagnostic accuracies near 100%. EV RNA sequencing revealed differential gene expression and fusion events linked to metastatic progression and long-term outcomes.

Conclusion: Liquid biopsy holds strong potential for transforming bone tumor care. Its clinical adoption depends on further validation through standardized methods and large-scale studies.

Introduction: Isatin derivatives are an important class of nitrogen-containing heterocyclic compounds that have exhibited a broad spectrum of pharmacological and biological activities. The condensation reaction of isatin readily forms C=N-bonded compounds due to the high reactivity of the 3-position carbonyl group. Hydrazone compounds also play an important role in research related to pesticide chemistry and medicinal chemistry. Therefore, we propose that the compound incorporates both indigo and hydrazone skeletons, which could confer excellent biological activity. The objective of this study is to synthesize novel isatinhydrazone derivatives that function as CDK2 inhibitors through molecular docking and bioactivity studies.

Methods: A series of isatin-hydrazone derivatives was synthesized and characterized using ¹H NMR, ¹³C NMR, and HRMS. The in vitro cytotoxicities of these compounds were assessed using an MTT assay against A549 (non-small cell lung cancer), HepG2 (hepatocellular carcinoma), and HeLa (cervical cancer) cell lines.

Results: According to the results of the MTT assay, compounds 2e and 2f exhibited potent selectivity and activity against A549 (IC₅₀ = 5 nM) and HeLa cells (IC₅₀ = 6 nM), respectively. Compound 2h demonstrated dual efficacy against A549 (IC₅₀= 8 nM) and HepG2 (IC₅₀= 13 nM). In addition, molecular docking revealed strong binding affinities and stable interactions between active derivatives and key residues within the CDK2 active site.

Conclusion: These novel isatin-hydrazone derivatives, particularly 2e, 2f, and 2h, could be used as potential anticancer agents that inhibit CDK2 kinase activity.

Introduction: During the last 20 years, the prevalence of colon cancer, among the most prevalent gastrointestinal cancers globally, has increased in the majority of nations. The current review compiled phytochemicals reported to manage colon cancer from 2015 to 2020.

Methods: The article is taken from various sources of Web of Science, PubMed, Google Scholar, Scopus, Elsevier, Research Gate, and PubChem Results: Colon cancer is the leading cause of cancer-related death worldwide and impacts both men and women. Because of the present dietary habits and lifestyle, which include eating a lot of meat, drinking alcohol, and not exercising enough, the death rate from colon cancer has increased globally. A robust gastrointestinal tract and the control of regular intestinal activity seem to be significantly influenced by dietary fiber.

Discussion: The prognosis for colon cancer is dismal, as it is frequently discovered at an advanced stage. Despite some evidence suggesting a diet low in fibre predisposes to colon carcinogenesis. The use of phytochemicals may help in the management of colon cancer.

Conclusion: By altering many signalling pathways involved in the control of chronic inflammation, the cell cycle, autophagy, apoptotic metastasis, and angiogenesis, these natural compounds have been shown to have anticolon cancer properties. Compounds such as Ellagitannin, Ursolic acid, Garcinol, Oxymatrine, Emodin, Catalpol, Resveratrol, Zerumbone, Curcumin, Pyrogallol, α-Hederin, Juglone, Zingerone, Brosimone I, Organosilicon, Myricetin, Tenacissoside H, 6,8-Diprenylorobol, Plumbagin, Dioscin, and many more are listed with their mechanisms of action.

Introduction: Skin cancer is a major global health concern, with rising prevalence and limited effectiveness of conventional therapies. Natural phytopharmaceuticals, particularly those derived from Triticum aestivum (wheatgrass), offer promising therapeutic potential due to their antioxidant, anti-inflammatory, and anticancer properties. This review explores the potential of nanogel-encapsulated wheatgrass bioactives to modulate molecular pathways involved in skin cancer development.

Methods: A comprehensive review was conducted of preclinical studies, advances in nanogel-based delivery systems, and the molecular pharmacology of wheatgrass phytoconstituents. Emphasis was placed on their interactions with key cancer-related signaling pathways and the impact of nanogels on pharmacokinetic and pharmacodynamic profiles.

Results: Wheatgrass bioactives were found to regulate oncogenic pathways, including PI3K/Akt, MAPK/ERK, NF-κB, and p53. Nanogel encapsulation enhanced solubility, stability, targeted delivery, and bioavailability. Both in vitro and in vivo studies demonstrated improved cytotoxicity against melanoma and non-melanoma skin cancer cells, with reduced off-target effects.

Discussion: Nanogel-based delivery of wheatgrass phytopharmaceuticals offers a multi-targeted strategy by modulating multiple cancer pathways while addressing challenges associated with natural compound delivery. Despite promising preclinical results, translational limitations remain, including scarce human trials and variability in formulation. Future research should prioritize clinical validation and regulatory standardization.

Conclusion: Nanogel-encapsulated wheatgrass bioactives represent a novel, mechanism-driven, and targetspecific approach for skin cancer therapy, with the potential to advance phytotherapy toward mainstream oncology treatment.

Introduction: Heterocyclic compounds are widely utilized in the development of anticancer medications due to their diverse structures and ability to interact with multiple biological targets within cancer cells. Quinoline is a heterocyclic compound and an essential compound in the domains of industrial and pharmaceutical chemistry because of its various pharmacological effects. Researchers are developing new traditional, synthetic, and innovative green approaches to synthesize mono- or poly-substituted quinoline derivatives for anticancer activity.

Methods: A comprehensive literature survey was conducted using multiple databases, including Google Scholar, PubMed, SpringerLink, ScienceDirect, and others, to investigate the existing literature on synthetic strategies for various quinoline derivatives. This review article intends to present a summary of various traditional synthetic methods alongside innovative green approaches.

Results: Many researchers have demonstrated that quinoline derivatives can be synthesized using various methods, including traditional techniques, hybrid approaches with heterocyclic structures, and innovative green synthetic methods, as well as elucidating their structure-activity relationships for potential use as anticancer agents. The majority of traditional synthetic methods rely on hazardous chemicals, low reaction rates, high temperatures, and high pressures. Currently, the green chemistry approach produces eco-friendly, economical, highyield, pure, and outstanding products in the fields of industry and pharmaceuticals.

Discussion: This section explores various affordable and eco-friendly synthetic techniques that produce potent and specific quinoline compounds, intended for use as anticancer agents.

Conclusion: The progress demonstrated in the green synthetic methods and the development of quinoline-based compounds as new treatment options could aid in identifying new and effective quinoline derivatives for cancer treatment in the future.

Introduction: Breast cancer remains a leading cause of cancer-related mortality in women, primarily due to Breast Cancer Stem Cells (BCSCs), which contribute to tumor progression, metastasis, and resistance to conventional therapies. Vitex negundo Linn. (VN), a medicinal plant abundant in polyphenolic flavonoids such as luteolin (LT), has previously demonstrated anticancer potential. This study investigates the active metabolite profiling of VN targeting BCSCs and evaluates LT's therapeutic potential through in vitro and in silico approaches.

Methods: An integrated network pharmacology and computational approach identified VN metabolites targeting BCSCs, including CDK1, cyclin B1/B2, TOP1, GSK-3β, and PARP1. Mutational analysis in MCF-7 cells followed by luteolin (LT) treatment assessed its impact on stemness, gene expression, ROS generation, cell cycle, and apoptosis. Molecular docking and dynamics confirmed LT's strong binding to CDK1/Cyclin B.

Results: LT significantly reduced the properties of BCSCs by inhibiting the CDK1/Cyclin B complex and downregulating associated genes. It induced ROS-mediated apoptosis and altered cell cycle distribution, notably increasing G1 and S phase populations. Molecular modeling confirmed strong binding of LT to CDK1/Cyclin B, suggesting disruption of cell cycle regulation and self-renewal.

Discussion: LT binds strongly to CDK1 and Cyclin B proteins, suppressing their activity in MCF-7 cells. This disrupts gene expression linked to BCSC self-renewal, induces apoptosis, and causes cell cycle arrest. LT targeting CDK1/Cyclin B complexes offers promising therapeutic potential for future clinical development against BCSCs.

Conclusion: LT from VN shows promise as a therapeutic agent targeting CDK1/Cyclin B in ER+ breast cancer stem cells, supporting its potential for clinical development.