Search Results (19)

Natural compounds with significant bioactive properties can be found in abundance within biomasses. Especially prominent for their anti-inflammatory, neuroprotective, antibacterial, and antioxidant activities are cinnamic acid derivatives (CAs). Ferulic acid (FA), a widely studied phenylpropanoid, exhibits a broad range of therapeutic and nutraceutical applications, demonstrating antidiabetic, anticancer, antimicrobial, and hepato- and neuroprotective activities. This research investigates the green enzymatic synthesis of innovative and potentially bifunctional prodrug derivatives of FA, designed to enhance solubility and stability profiles. Selective esterification was employed to conjugate FA with xylitol, a biobased polyol recognized for its bioactive antioxidant properties and safety profile. Furthermore, by exploiting t-amyl alcohol as a green solvent, the enzymatic synthesis of the derivative was optimized for reaction parameters including temperature, reaction time, enzyme concentration, and molar ratio. The synthesized derivative, xylitol monoferulate (XMF), represents a novel contribution to the literature. The comprehensive characterization of this compound was achieved using advanced spectroscopic methods, including ¹H-NMR, ¹³C-NMR, COSY, HSQC, and HMBC. This study represents a significant advancement in the enzymatic synthesis of high-value biobased derivatives, demonstrating increased biological activities and setting the stage for future applications in green chemistry and the sustainable production of bioactive compounds. Full article

Resveratrol is a natural polyphenol (stilbenoid), which can be found in grape skin, red wine, blueberries, peanuts and others. The biological properties of resveratrol, in particular antioxidant, anti-inflammatory, anticancer, estrogenic, vasorelaxant and cardioprotective activity, are the main reason for its importance in medicine and pharmacy. Despite all of its advantages, however, there are many problems related to this polyphenolic substance, such as low stability, water insolubility, poor bioavailability and fast metabolism. For this reason, scientists are currently searching for different approaches to dealing with these problematic properties and improving the therapeutic usage of resveratrol. This review summarizes the mechanisms of the biological effects of resveratrol, determined in vitro and in vivo, and the main limitations of the drug. The article emphasizes new approaches for the improvement of resveratrol delivery, in particular nanoencapsulation, formation of nanocrystals, prodrugs and structure analogues. Full article

Monoamine oxidase B (MAO-B) is a key enzyme in the mitochondrial outer membrane, pivotal for the oxidative deamination of biogenic amines. Its overexpression has been implicated in the pathogenesis of several cancers, including glioblastoma and colorectal, lung, renal, and bladder cancers, primarily through the increased production of reactive oxygen species (ROS). Inhibition of MAO-B impedes cell proliferation, making it a potential therapeutic target. Various monoamine oxidase B inhibitors have shown promise in inhibiting tumor growth and inducing apoptosis across different cancer types. In this review, we investigate MAO-B network biology, which highlighted glycolysis pathways as notable links between MAO-B and cancer. Further molecular modeling analysis illustrated the basis of MAO-B ligand binding, revealing a hydrophobic binding pocket, with key residues such as Tyr398 and Tyr435 playing crucial roles in substrate oxidation. MAO-B inhibitors that were reportsed in the literature (2012–2024) and their potential application in cancer therapy were discussed, highlighting key molecular scaffolds, such as propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B activated pro-drugs, and natural phenylpropanoid derivatives. The reported literature underscores the therapeutic potential of MAO-B inhibitors as versatile anticancer agents, warranting further investigation to optimize their efficacy and specificity across various malignancies. Full article

Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H₂O₂ evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new “green” carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations. Full article

Pt^IV coordination complexes are of interest as prodrugs of Pt^II anticancer agents, as they can avoid deactivation pathways owing to their inert nature. Here, we report the oxidation of the antitumor agent [Pt^II(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)], 1 (py = pyridine) to dihydroxidoplatinum(IV) solvate complexes [Pt^IV{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(OH)₂(py)].H₂O, 2·H₂O with hydrogen peroxide (H₂O₂) at room temperature. To optimize the yield, 1 was oxidized in the presence of added lithium chloride with H₂O₂ in a 1:2 ratio of Pt: H₂O_2, in CH₂Cl₂ producing complex 2·H₂O in higher yields in both gold and red forms. Despite the color difference, red and yellow 2·H₂O have the same structure as determined by single-crystal and X-ray powder diffraction, namely, an octahedral ligand array with a chelating organoamide, pyridine and chloride ligands in the equatorial plane, and axial hydroxido ligands. When tetrabutylammonium chloride was used as a chloride source, in CH₂Cl₂, another solvate, [Pt^IV{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(OH)₂(py)].0.5CH₂Cl_2,3·0.5CH₂Cl₂, was obtained. These Pt^IV compounds show reductive dehydration into Pt^II [Pt{(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)], 1H over time in the solid state, as determined by X-ray powder diffraction, and in solution, as determined by ¹H and ¹⁹F NMR spectroscopy and mass spectrometry. 1H contains an oxidized coordinating ligand and was previously obtained by oxidation of 1 under more vigorous conditions. Experimental data suggest that oxidation of the ligand is favored in the presence of excess H₂O₂ and elevated temperatures. In contrast, a smaller amount (1Pt:2H₂O₂) of H₂O₂ at room temperature favors the oxidation of the metal and yields platinum(IV) complexes. Full article

Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field. Full article

Drug resistance presents a major obstacle to the successful treatment of glioblastoma. Autophagy plays a key role in drug resistance, particularly in relation to targeted therapy, which has prompted the use of autophagy inhibitors to increase the effectiveness of targeted therapeutics. The ability of two Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306, to induce autophagy was evaluated in the human glioblastoma cell line U87 and its multidrug-resistant counterpart U87-TxR. Autophagy markers were assessed by flow cytometry, microscopy, and Western blot, and induction of autophagy by these compounds was demonstrated after 3 h as well as 48 h. The effects of Si306 and pro-Si306 on cell proliferation and cell death were examined in the presence or absence of autophagy inhibition by bafilomycin A1. Combined treatments of Si306 and pro-Si306 with bafilomycin A1 were synergistic in nature, and the inhibition of autophagy sensitized glioblastoma cells to Src tyrosine kinase inhibitors. Si306 and pro-Si306 more strongly inhibited cell proliferation and triggered necrosis in combination with bafilomycin A1. Our findings suggest that modulation of Si306- and pro-Si306-induced autophagy can be used to enhance the anticancer effects of these Src tyrosine kinase inhibitors and overcome the drug-resistant phenotype in glioblastoma cells. Full article

Natural prodrugs extracted from plants are increasingly used in many sectors, including the pharmaceutical, cosmetic, and food industries. Among these prodrugs, essential oils (EOs) are of particular importance. These biologically active volatile oily liquids are produced by medicinal and aromatic plants and characterized by a distinctive odor. EOs possess high anticancer, antibacterial, antiviral, and antioxidant potential but often are associated with low stability; high volatility; and a high risk of deterioration with exposure to heat, humidity, light, or oxygen. Furthermore, their bioavailability is limited because they are not soluble in water, and enhancements are needed to increase their potential to target specific cells or tissues, as well as for controlled release. Nanomedicine, the application of nanotechnology in medicine, may offer efficient solutions to these problems. The technology is based on creating nanostructures in which the natural prodrug is connected to or encapsulated in nanoparticles or submicron-sized capsules that ensure their solubility in water and their targeting properties, as well as controlled delivery. The potential of EOs as anticancer prodrugs is considerable but not fully exploited. This review focusses on the recent progress towards the practical application of EOs in cancer therapy based on nanotechnology applications. Full article

Albumin has shown remarkable promise as a natural drug carrier by improving pharmacokinetic (PK) profiles of anticancer drugs for tumor-targeted delivery. The exogenous or endogenous albumin enhances the circulatory half-lives of anticancer drugs and passively target the tumors by the enhanced permeability and retention (EPR) effect. Thus, the albumin-based drug delivery leads to a potent antitumor efficacy in various preclinical models, and several candidates have been evaluated clinically. The most successful example is Abraxane, an exogenous human serum albumin (HSA)-bound paclitaxel formulation approved by the FDA and used to treat locally advanced or metastatic tumors. However, additional clinical translation of exogenous albumin formulations has not been approved to date because of their unexpectedly low delivery efficiency, which can increase the risk of systemic toxicity. To overcome these limitations, several prodrugs binding endogenous albumin covalently have been investigated owing to distinct advantages for a safe and more effective drug delivery. In this review, we give account of the different albumin-based drug delivery systems, from laboratory investigations to clinical applications, and their potential challenges, and the outlook for clinical translation is discussed. In addition, recent advances and progress of albumin-binding drugs to move more closely to the clinical settings are outlined. Full article

Chemodynamic therapy (CDT) based on intracellular Fenton reactions is attracting increasing interest in cancer treatment. A simple and novel method to regulate the tumor microenvironment for improved CDT with satisfactory effectiveness is urgently needed. Therefore, glutathione (GSH)/ROS (reactive oxygen species) dual-responsive supramolecular nanoparticles (GOx@BNPs) for chemo–chemodynamic combination therapy were constructed via host–guest complexation between water-soluble pillar[6]arene and the ferrocene-modified natural anticancer product betulinic acid (BA) prodrug, followed by encapsulation of glucose oxidase (GOx) in the nanoparticles. The novel supramolecular nanoparticles could be activated by the overexpressed GSH and ROS in the tumor microenvironment (TME), not only accelerating the dissociation of nanoparticles—and, thus, improving the BA recovery and release capability in tumors—but also showing the high-efficiency conversion of glucose into hydroxyl radicals (·OH) in succession through intracellular Fenton reactions. Investigation of antitumor activity and mechanisms revealed that the dramatic suppression of cancer cell growth induced by GOx@BNPs was derived from the elevation of ROS, decrease in ATP and mitochondrial transmembrane potential (MTP) and, finally, cell apoptosis. This work presents a novel method for the regulation of the tumor microenvironment for improved CDT, and the preparation of novel GSH/ROS dual-responsive supramolecular nanoparticles, which could exert significant cytotoxicity against cancer cells through the synergistic interaction of chemodynamic therapy, starvation therapy, and chemotherapy (CDT/ST/CT). Full article

Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems. Full article

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use. Full article

Cancer is a serious threat to human health. With the increasing resistance to known drugs, it is still urgent to find new drugs or pro-drugs with anti-tumor effects. Natural products produced by microorganisms have played an important role in the history of drug discovery, particularly in the anticancer and anti-infective areas. The plant rhizosphere ecosystem is a rich resource for the discovery of actinomycetes with potential applications in pharmaceutical science, especially Streptomyces. We screened Streptomyces-like strains from the rhizosphere soil of wheat (Triticum aestivum L.) in Hebei province, China, and thirty-nine strains were obtained. Among them, the extracts of 14 isolates inhibited the growth of colon tumor cell line HCT-116. Strain NEAU-wh-3-1 exhibited better inhibitory activity, and its active ingredients were further studied. Then, 16S rRNA gene sequence similarity studies showed that strain NEAU-wh3-1 with high sequence similarities to Embleya scabrispora DSM 41855^T (99.65%), Embleya hyalina MB891-A1^T (99.45%), and Streptomyces lasii 5H-CA11^T (98.62%). Moreover, multilocus sequence analysis based on the five other house-keeping genes (atpD, gyrB, rpoB, recA, and trpB) and polyphasic taxonomic approach comprising chemotaxonomic, phylogenetic, morphological, and physiological characterization indicated that the isolate should be assigned to the genus Embleya and was different from its closely related strains, therefore, it is proposed that strain NEAU-wh3-1 may be classified as representatives of a novel species of the genus Embleya. Furthermore, active substances in the fermentation broth of strain NEAU-wh-3-1 were isolated by bioassay-guided analysis and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses. Consequently, one new Zincophorin analogue together with seven known compounds was detected. The new compound showed highest antitumor activity against three human cell lines with the 50% inhibition (IC₅₀) values of 8.8–11.6 μg/mL and good antibacterial activity against four pathogenic bacteria, the other known compounds also exhibit certain biological activity. Full article

Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer. Full article

Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (~60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug. Full article