Current Medicinal Chemistry - Volume 32, Issue 11, 2025

ATP-binding cassette transporter A1 (ABCA1) is one of the key proteins regulating cholesterol homeostasis and playing a crucial role in atherosclerosis development. ABCA1 regulates the rate-limiting step of reverse cholesterol transport, facilitates the efflux of surplus intracellular cholesterol and phospholipids, and suppresses inflammation through several signalling pathways. At the same time, many mutations and Single Nucleotide Polymorphisms (SNPs) have been identified in the ABCA1 gene, which affects its biological function and is associated with several hereditary diseases (such as familial hypo-alpha-lipoproteinaemia and Tangier disease) and increased risk of cardiovascular diseases (CVDs). This review summarises recently identified mutations and SNPs in their connection to atherosclerosis and associated CVDs. Also, we discuss the recently described application of various plant-derived compounds to modulate ABCA1 expression in different in vitro and in vivo models. Herein, we present a comprehensive overview of the association of ABCA1 mutations and SNPs with CVDs and as a pharmacological target for different natural-derived compounds and highlight the potential application of these phytochemicals for treating atherosclerosis through modulation of ABCA1 expression.

Pleural mesothelioma is a rare neoplastic disease with aggressive features. Patient survival is poor due to the lack of early symptoms and the absence of effective therapeutic strategies. The development of pleural mesothelioma is mainly associated to asbestos exposure and related chronic inflammation. From a molecular-based perspective, this disease is a heterogeneous tumor lacking actionable alterations. The median overall survival of patients affected by this tumor does not exceed 16 months from diagnosis. Molecular and biochemical approaches have shown that this disease is characterized by resistance to drug-induced apoptosis associated with the activation of cell survival pathways and expression of anti-apoptotic proteins. Thus, there is an urgent need to develop efficient and safe therapeutic strategies. Here, we review the pharmacological options available for the treatment of this disease with specific reference to the antitumor agents used in systemic therapies. In addition, novel pharmacological approaches, such as drug delivery tools, to improve pleural mesothelioma treatment are discussed.

α-Glucosidase inhibitors (AGIs) showcase versatile biochemical activities with respect to antidiabetic, anticancerous, antiobese and antiviral effects. They have drawn a great deal of attention from the scientific community. While α-glucosidase inhibitors are mostly discovered from plants and microorganisms, the recent advance in natural α-glucosidase inhibitors over the past five years has been reviewed in this article, and 139 distinct α-glucosidase inhibitors from the plants and microorganisms were classified into ten groups based on their chemical structures, including flavonoids (34), xanthones (6), alkaloids (8), benzopyrones / benzofuranones (8), terpenes (25), saponins (6), phenols / alcohols (25), esters (20), chalcone (5) and other compounds (2). In this review, we mainly focused on the novel chemical structures and the various biological activities of theses natural AGIs. Some of the selected natural compounds exhibit powerful α-glucosidase inhibitory activity and anti-tumor activity, may hold promise to become the candidate drugs for treating type II diabetes and cancer in future.

Several investigations have revealed that nasopharyngeal carcinoma (NPC), earlier known as lymphoepithelioma, originates from the nasopharynx epithelium (NPE). The global NPC incidence and mortality distribution reports have reported very high rates (more than 20-30 men per 100,000 men and 10 women per 100,000). Genetic background susceptibilities, Epstein-Barr virus (EBV), and their complex interaction are expressed as the pathophysiology. Also, radiotherapy of locoregional lesions is the main treatment for NPC because of the extremely radiosensitive feature of the non-keratinizing variety. On the other hand, surgical intervention might be used for recurrent situations, while simultaneous radiation and chemotherapy for advanced stages are preferable. Since specific disease symptoms do not appear early, biomarkers should be identified to facilitate diagnosis. As overexpression of heat shock proteins (HSPs) has been observed in various cancers, they can be a promising candidate biomarker for many malignancies. The purpose of this study was to peruse different pathogenic roles of a panel of HSPs, including their diagnostic, preventive, and remedial role in NPC, which may provide the basis for future discoveries of novel HSP-based biomarkers of NPC.

Conventional therapeutic modalities against the cancers such as surgery, chemotherapy (CT) and radiotherapy (RT) have limited efficacy due to drug resistance, and adverse effects. Recent developments in nanoscience emphasized novel approaches to overcome the aforementioned limitations and subsequently improve overall clinical outcomes in cancer patients. Photodynamic therapy (PDT), photothermal therapy (PTT), and radiodynamic therapy (RDT) can be used as cancer treatments due to their high selectivity, low drug resistance, and low toxicity. Mitocans are the therapeutic molecules that can produce anti-cancer effects by modulating mitochondria functions and they have significant implications in cancer therapy. Mitochondria- targeted therapy is a promising strategy in cancer treatment as these organelles play a crucial function in the regulation of apoptosis and metabolism in tumor cells and are more vulnerable to hyperthermia and oxidative damage. The aim of this review is used to explore the targeting efficacy of mitocans in the nanotherapeutic formulation when combined with therapies like PDT, PTT, RDT. We searched several databases include Pubmed, relemed, scopus, google scholar, Embase and collected the related information to the efficacy of mitocans in nanotherapeutics when combined with photo-radiotherapy to target chemo/radio-resisant tumor cells. In this review, we vividly described research reports pertinent to the selective delivery of chemotherapy molecules into specific sub-organelles which can significantly improve the efficiency of cancer treatment by targeting tumor cell metabolism. Furthermore, the rational design, functionalization and application of various mitochondrial targeting units, including organic phosphine/sulfur salts, quaternary ammonium salts, transition metal complexes, and mitochondria-targeted cancer therapy such as PDT, PTT, RDT, and others were summarized. Mainly, the efficacy of these modalities against mtDNA and additional nanotherapeutic strategies with photosensitizers, or radiotherapy to target mitochondrial metabolism in tumor cells with chemo/radio-resistance were delineated. This review can benefit nanotechnologists, oncologists, and radiation oncologists to develop rational designs and application of novel mitochondrial targeting drugs mainly to target metabolism in chemo/radio-resistant cancer cells in cancer therapy.

Today, one of the most prevalent reasons for death among people is carcinoma. Because it is still on the increase throughout the world, there is a critical need for in-depth research on the pathogenic mechanisms behind the disease as well as for efficient treatment. In the field of epigenetics, gene expression alterations that are inherited but not DNA sequence changes are investigated. Three key epigenetic changes, histone modifications, DNA methylation and non-coding RNA (ncRNA) expression, are principally responsible for the initiation and progression of different tumors. These changes are interconnected and constitute many epigenetic changes. A form of polyphenolic chemical obtained from plants called curcumin has great bioactivity against several diseases, specifically cancer. A naturally occurring substance called thymoquinone is well-known for its anticancer properties. Thymoquinone affects cancer cells through a variety of methods, according to preclinical studies. We retrieved information from popular databases, including PubMed, Google Scholar, and CNKI, to summarize current advancements in the efficiency of curcumin against cancer and its epigenetic regulation in terms of DNA methylation, histone modifications, and miRNA expression. The present investigation offers thorough insights into the molecular processes, based on epigenetic control, that underlie the clinical use of curcumin and thymoquinone in cancerous cells.

Diabetic coronary heart disease is a global medical problem that poses a serious threat to human health, and its pathogenesis is complex and interconnected. Nicotinamide adenine dinucleotide (NAD) is an important small molecule used in the body that serves as a coenzyme in redox reactions and as a substrate for non-redox processes. NAD levels are highly controlled by various pathways, and increasing evidence has shown that NAD pathways, including NAD precursors and key enzymes involved in NAD synthesis and catabolism, exert both positive and negative effects on the pathogenesis of diabetic coronary heart disease. Thus, the mechanisms by which the NAD pathway acts in diabetic coronary heart disease require further investigation. This review first briefly introduces the current understanding of the intertwined pathological mechanisms of diabetic coronary heart disease, including insulin resistance, dyslipidemia, oxidative stress, chronic inflammation, and intestinal flora dysbiosis. Then, we mainly review the relationships between NAD pathways, such as nicotinic acid, tryptophan, the kynurenine pathway, nicotinamide phosphoribosyltransferase, and sirtuins, and the pathogenic mechanisms of diabetic coronary heart disease. Moreover, we discuss the potential of targeting NAD pathways in the prevention and treatment of diabetic coronary heart disease, which may provide important strategies to modulate its progression.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Leishmaniasis is a neglected tropical disease caused by protozoa parasites from the Leishmania genus. Vertebrate hosts acquire the infection through the bite of a female sandfly, initiating a complex parasite development cycle. Contrary to previous beliefs regarding cats’ resistance, these animals have recently been identified as potential reservoirs for leishmaniasis. Clinical symptoms in cats can manifest in diverse forms, including cutaneous, mucocutaneous, and visceral manifestations. The diagnosis of feline leishmaniasis is complicated by nonspecific symptoms and the relatively lower specificity of serological tests. The recommended treatment for feline leishmaniasis involves the administration of medications; however, success varies in each cat. This review aims to present cases of feline leishmaniasis, highlighting clinical symptoms, diagnostic methods, therapy schedules, and outcomes. Among the 24 cases documented in the available literature, 12 achieved successful treatment without relapses, resulting in a reduced parasite load and improved symptoms. Three cases responded well but presented persistent sequelae. Two feline leishmaniasis cases initially had treatment success but later experienced recurrences. Finally, no response was observed in seven cases, leading to the euthanasia of cats due to ineffectiveness or irregularities along the therapy. Conventional treatments, despite potential hepatotoxicity and nephrotoxicity, exhibit a high efficacy in reducing parasitic load, thereby improving clinical symptoms and increasing the life expectancy of affected cats. Nevertheless, consistent adherence is crucial, as interruptions may render the therapy ineffective and contribute to parasite resistance. Therefore, addressing the challenges associated with feline leishmaniasis treatment necessitates the development of new strategies to ensure a more effective and sustained approach.