Current Medicinal Chemistry - Volume 32, Issue 22, 2025

Cancer, a diverse group of diseases characterized by abnormal cell growth and the potential to spread throughout the body, accounts for approximately 10 million deaths globally each year. Current cancer therapies, including chemotherapy, radiation, and various pharmacological treatments, present several challenges and potential side effects. It is important to differentiate these conventional methods, which often involve synthetic drugs, from adjuvant therapies that might be used in conjunction. As a result, there is an increasing interest in alternative therapies, particularly in agents derived from natural sources for cancer treatment. Secondary metabolites have shown promise in promoting the development of new clinical drugs with various anti-cancer mechanisms. This review focuses on the anti-cancer potential of the novel metabolite Andrographolide, extracted mainly from Andrographis paniculata. The chemopreventive properties and the ability to inhibit various signaling pathways across different types of cancers without side effects posit Andrographolide as a promising natural antitumour agent. The review identified that Andrographolide inhibits multiple signaling pathways, contributing to its anti-proliferative, anti-metastatic, and apoptotic effects in various cancers. The compound's natural origin and lack of adverse side effects make it particularly attractive as a therapeutic agent. However, further detailed studies are needed to fully understand its specific mechanisms and potential clinical applications. Andrographolide presents a compelling option as a natural anticancer agent with the potential to overcome some limitations of traditional cancer treatments. Its broad spectrum of anti-cancer activities and absence of side effects highlight its therapeutic potential. The review highlights that continued research and clinical studies are important for confirming the effectiveness and safety of Andrographolide in human use, alongside optimizing dosage and delivery techniques.

Cancer, a complicated and multi-dimensional medical concern worldwide, can be identified via either the growth of malignant tumours or colonisation of nearby tissues attributing to uncontrollable proliferation and division of cells promoted by several influential factors, including family history, exposure to pollutants, choice of lifestyle, and certain infections. The intricate processes underlying the development, expansion, and advancement of cancer are still being studied. However, there are a variety of therapeutic alternatives available for the diagnosis and treatment of cancer depending on the type and stage of cancer as well as the patient’s individuality. The bioactive compounds- fortified nanofiber-based advanced therapies are revolutionary models for cancer detection and treatment, specifically targeting melanoma cells via exploring unique properties, such as increased surface area for payload, and imaging and bio-sensing capacities of nano-structured materials with minimal damage to functioning organs. The objective of the study was to gain knowledge regarding the potentiality of Nanofibers (NFs) fabricated using biomaterials in promoting cancer management along with providing a thorough overview of recent developmental initiatives, challenges, and future investigation strategies. Several fabrication approaches, such as electrospinning, self-assembly, phase separation, drawing, and centrifugal spinning of bio-compatible NFs along with characterization techniques, have been elaborated in the review.

The current review was undertaken to collate data on Gpx4 inhibitors and the regulatory proteins related to Gpx4. Gpx4 plays an essential role in ferroptosis; it can be used to determine the Gpx4 as an indicator for determining tumor occurrence and as a means of treating cancer. Although there is no market for Gpx4 inhibitors, many researchers have conducted extensive research, and some compounds have entered clinical research. This article summarizes all papers related to Gpx4; hope this review can provide some new insights and ideas for researchers aiming to develop efficient and low- toxicity Gpx4 inhibitors and provide some new ideas for cancer treatment.

Gynecological cancers, encompassing endometrial, ovarian, and cervical cancer, pose significant challenges in clinical practice, often marked by high mortality rates and treatment resistance. Despite advances in standard therapies, including chemoradiation and surgery, tumor recurrence and metastasis remain formidable obstacles. In this context, there is a pressing need to explore novel therapeutic strategies that offer improved efficacy and reduced side effects. Herbal medicine, particularly compounds like resveratrol, has garnered attention for its diverse biological properties, including anticancer effects. Resveratrol, a multipotential nutraceutical, holds promise in gynecological cancer therapy through its modulation of key cellular and molecular processes. This review aims to provide an overview of the current status, challenges, and opportunities in utilizing resveratrol for gynecological cancer treatment. We discuss its role in miRNA regulation, clinical trial findings, and the development of effective formulations. By elucidating the underlying mechanisms of resveratrol's anticancer effects and exploring innovative delivery systems, we aim to shed light on the potential avenues for optimizing its therapeutic benefits in gynecological cancers.

Improvements in cancer treatment are largely influenced by more people knowing about it and developing new ways to diagnose and treat it. New methods such as nanotheranostics and the use of tiny particles have greatly improved the diagnosis, control and treatment of cancer. They have also helped overcome problems with traditional treatments. Nanotheranostics contribute to personalized medicine by helping doctors choose the right treatment, track how well the treatment works, and plan future treatments. Polymers have many advantages as smart or durable drug formulations among small therapeutic platforms. These small sacks, which can be used for drug delivery and imaging, are not harmful to natural tissues and are becoming more popular. Scientists have found a special group of tiny particles made of polymers that can carry active ingredients. These particles show the potential of creating a useful platform for the diagnosis and treatment of diseases on a very small scale. In the past ten years, people have become more interested in polymersomes. They have been used for various medical purposes, such as controlling blood sugar, treating cancer and fighting bacteria. Polymers are stronger and more stable than liposomes. Biocompatible and biodegradable polymers are very important for faster translation and creation of useful medical formulations. Recent progress in this field includes the creation of intelligent, centralized and responsive containers. In this review, we will examine and provide information about polymersomes. We will discuss their properties and how they can be used as drug delivery systems.

This review produces information about the role of protein phosphatase-6 (PPP6C) in various biological processes such as cell proliferation, cell cycle regulation, apoptosis, autophagy, cell migration and differentiation, and DNA damage repair. The issues of the participation of PPP6C in the formation of tumor progression and the role of PPP6C in the epigenetic regulation of the tumor process are covered. The article presents in detail the classification of mutations depending on the biological effects they have. It has been shown that various types of mutations in the PPP6C gene can change the composition of the heterotrimeric complex, favoring some regulatory subunits over others, which promotes selective dephosphorylation of substrates to maintain cell viability and change their biological behavior. In particular, their proliferative activity is disrupted, leading to mitosis arrest at various cell cycle stages. An increase in the activity of Aurora A or a decrease in the activity of DNA-dependent protein kinase is considered the main molecular mechanism of tumor development associated with the inactivation of the pp6c protein. The article also discusses the topic of pharmacological modulation of PPP6C activity. PP6 is a protein involved in many biological processes. In this regard, it is especially important to clarify the role of each PP6 holoenzyme and the molecular mechanisms that regulate the formation of the PP6 complex. Changes in the activity of this phosphatase can disrupt cell functioning.

Depression is a common mental illness that damages the life and health of patients and causes economic burden, and HPA (hypothalamic-pituitary-adrenal) axis dysfunction is considered to be one of the important factors leading to depression. In this case, it is essential to explore possible treatment methods by using natural compounds with HPA axis regulating and antidepressant effects. However, no one has reviewed it so far. Therefore, the purpose of this review is to systematically sort out the related natural products that play an antidepressant role by regulating the function of the HPA axis. Natural products are divided into flavonoids, polyphenols, terpenoids, saponins, polysaccharides and so on according to their chemical structures, which play a variety of biological activities such as regulating the HPA axis, anti-inflammation and neuroprotection. These effects may provide a useful reference for the potential treatment of depression so as to develop new antidepressants.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) belongs to a member of the proprotein convertase (PC) family, which is mainly secreted by the liver and plays a central role in lipid metabolism. Furthermore, PCSK9 plays a multifunctional role in promoting the inflammatory response, inducing cell apoptosis and pyroptosis and affecting tumor homeostasis. The brain is the organ with the richest lipid content. Incidentally, PCSK9 increased in many brain diseases, including brain injury and Alzheimer’s disease (AD). Consequently, the relationship between PCSK9 and brain diseases has attracted increasing research interest. Amyloid beta (Aβ) accumulation is the central and initial event in the pathogenesis of AD. This study focuses on the effects of PCSK9 on Aβ accumulation in the brain via multiple modalities to explore the potential role of PCSK9 in AD, which is characterized by progressive loss of brain cells by increasing Aβ accumulation. The study also explores the new mechanism by which PCSK9 is involved in the pathogenesis of AD, providing interesting and innovative guidance for the future of PCSK9-targeted therapy for AD.

Previous studies described that asthma patients who received corticosteroid therapy have been constrained by the corticosteroid resistance subsequently fostered to severe refractory asthma. In this review, we discussed the implications of TSLP, RXR, the role of STAT5-activating cytokines, and IL-33/NH-cell signaling pathways, and recent clinical evidence on TSLP blockers in steroid-resistant asthma. We have searched several public databases such as Pubmed, Scopus, and Relemed and obtained information pertinent to the TSLP, RXR, TSLP blockers, the STAT5-activating cytokines, and IL-33. We discussed the multiple cell signaling mechanisms underlying steroid resistance. Blocking the TSLP and other key signaling molecules like STAT5 can retrieve the sensitivity of natural helper-cells to corticosteroids. RXR derivatives treatment can modulate the activity of TSLP, which further modulates steroid resistance in severe asthmatic patients and in patients with refractory asthma. We discussed the steroid-resistance mediated by the Th2 cells and Th2-driven eosinophilia upon corticosteroid intake. Thus, this review will be beneficial for clinicians and molecular biologists to explore the inflammatory pathways associated with refractory asthma conditions and develop novel therapies against corticosteroid-resistant asthma.