Search

Cancer stands as a leading cause of global mortality, with chemotherapy being a pivotal treatment approach, either alone or in conjunction with other therapies. The primary goal of these therapies is to inhibit the growth of cancer cells specifically, while minimizing harm to healthy dividing cells. Conventional treatments, often causing patient discomfort due to side effects, have led researchers to explore innovative, targeted cancer cell therapies. Thus, biopolymer‐based aerogels emerge as innovative platforms, showcasing unique properties that respond intelligently to diverse stimuli. This responsiveness enables precise control over the release of anticancer drugs, enhancing therapeutic outcomes. The significance of these aerogels lies in their ability to offer targeted drug delivery with increased efficacy, biocompatibility, and a high drug payload. In this comprehensive review, the author discuss the role of biopolymer‐based aerogels as an emerging functionalized platforms in anticancer drug delivery. The review addresses the unique properties of biopolymer‐based aerogels showing their smart behavior in responding to different stimuli including temperature, pH, magnetic and redox potential to control anticancer drug release. Finally, the review discusses the application of different biopolymer‐based aerogel in delivering different anticancer drugs and also discusses the potential of these platforms in gene delivery applications. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this work was to assess failures in the advanced prescription of parenteral anticancer agents in an adult day oncology care unit with more than 100 patients per day. Methods: An a priori descriptive analysis was carried out by using the risk matrix approach. After defining the scope in a multidisciplinary meeting, we determined at each step the failure modes (FMs), their effects (E) and their associated causes (C). A severity score (S) was assigned to all effects and a probability of occurrence (O) to all causes. These S and O indicators, were used to obtain a criticality index (CI) matrix. We assessed the risk control (RC) of each failure in order to define a residual criticality index (rCI) matrix. Results: During risk analysis, 14 FMs were detected, and 61 scenarios were identified considering all possible effects and causes. Nine situations (15%) were highlighted with the maximum CI, 18 (30%) with a medium CI, and 34 (55%) with a negligible CI. Nevertheless, among all these critical situations, only three (5%) had an rCI to process (i.e., missed dose adjustment, multiple prescriptions and abnormal biology data); the others required monitoring only. Clinicians' and pharmacists' knowledge of these critical situations enables them to manage the associated risks. Conclusions: Advanced prescription of injectable anticancer drugs appears to be a safe practice for patients when combined with risk management. The major risks identified concerned missed dose adjustment, prescription duplication and lack of consideration for abnormal biology data. [ABSTRACT FROM AUTHOR]

This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products. [ABSTRACT FROM AUTHOR]

The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein, we apply combinatorial synthesis to build a library of 90 iridium(III) complexes (81 of which are new) over two synthesise‐and‐test cycles, with the aim of identifying potential agents for photodynamic therapy. We demonstrate the power of this approach by identifying highly active complexes that are well‐tolerated in the dark but display very low nM phototoxicity against cancer cells. To build a detailed structure–activity relationship for this class of compounds we have used density functional theory (DFT) calculations to determine some key electronic parameters and study correlations with the experimental data. Finally, we present an optimised semi‐automated synthesise‐and‐test protocol to obtain multiplex data within 72 hours. [ABSTRACT FROM AUTHOR]

The problem of tumour therapy has attracted the attention of many researchers for many decades. One of the promising strategies for the development of new dosage forms to improve oncology treatment efficacy and minimise side effects is the development of nanoparticle-based targeted transport systems for anticancer drugs. Among inorganic nanoparticles, mesoporous silica deserves special attention due to its outstanding surface properties and drug-loading capability. This review analyses the various factors affecting the cytotoxicity, cellular uptake, and biocompatibility of mesoporous silica nanoparticles (MSNs), constituting a key aspect in the development of safe and effective drug delivery systems. Special attention is paid to technological approaches to chemically modifying MSNs to alter their surface properties. The stimuli that regulate drug release from nanoparticles are also discussed, contributing to the effective control of the delivery process in the body. The findings emphasise the importance of modifying MSNs with different surface functional groups, bio-recognisable molecules, and polymers for their potential use in anticancer drug delivery systems. [ABSTRACT FROM AUTHOR]

One of the most typical cancers to affect women worldwide is breast cancer. Multiple routes involving different proteins that control the development of cancer. HER-2 is a protein that contributes to the progression of breast cancer cells. This study uses n-phenyl pyrazoline derivate compounds. The predictive binding of several forms of pyrazoline compounds to HER-2 was analyzed using docking analysis in an in silico model. Pyrazoline A, B, C, D, and M were used as ligands, and neratinib as a commercial drug. Pyrazoline C was the ligand with the highest affinity (-109.218 Kcal/mol) if compared with native ligand 03Q (-170.697 Kcal/mol) and neratinib (-83.416 Kcal/mol). Pyrazoline C has the potential to develop as a breast cancer drug with COX-2 inhibitory activity. The molecular dynamics simulation for 50 ns showed that RMSD, RMSF, and SASA are rigid and stable. Pyrazoline C has the potential to develop as a breast cancer drug with HER-2 inhibitory activity. [ABSTRACT FROM AUTHOR]

Background/Purpose of the Study The costs of chemotherapy drugs which are vital in the treatment of lung cancer can be exorbitant. The current study was undertaken to ascertain cost minimization analysis by comparing costliest and cheapest branded with Jan Aushadhi (JA) drugs marketed in India. Methods The cost of costliest, cheapest branded, and JA drugs were collected from the designated reference sites. The cost difference, cost ratio, and percentage of cost variation were calculated as per cost minimization study guidelines. Results The results of the analysis suggest that the JA drugs were much cheaper than the branded drugs and when used in regimens resulted in substantial cost savings. The biggest financial advantage was seen in the commonly used cisplatin–pemetrexed regimen where cost saving of Rs. 268,002 was observed for the whole treatment of six cycles. Using JA drugs also reduced the cost for the targeted therapy with gefitinib and erlotinib. Conclusion The cost minimization study, which is the first in this field of lung cancer, clearly indicates the usefulness of JA drugs in reducing financial costs for the patient. [ABSTRACT FROM AUTHOR]

Aims: CG‐750 is an oral formulation of ivaltinostat, a newly developing histone deacetylase (HDAC) inhibitor. This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of an oral formulation (CG‐750) of ivaltinostat compared to an intravenous (IV) formulation (CG‐745). Methods: A randomized, double‐blind, placebo‐controlled study was conducted in three cohorts. Subjects received either CG‐745 (Cohorts 1 and 3: 125 mg; Cohort 2: 250 mg) or placebo followed by CG‐750 (Cohort 1: 125 mg; Cohort 2: 375 mg; Cohort 3: 750 mg) or placebo. Blood samples for PK and PD assessment were collected up to 72 h post‐dose. Histone H3 acetylation at sites K9, K9/K14 and K27 was assessed for area under the % acetylation induction versus time curve (AUEC). Results: A total of 25 subjects were randomized, and 23 subjects completed the study (Cohort 1, n = 6; Cohort 2, n = 6; Cohort 3, n = 6; placebo, n = 5). The mean bioavailability of CG‐750 was 10.6% (range: 4.18%–21.33%) and displayed linear PK in the dose range of 125–750 mg. The comparison of AUEC between formulations and the evaluation of the dose–AUEC relationship were inconclusive, due to the small sample sizes and significant variability observed in PD markers. All adverse events (AEs) were transient and of mild or moderate intensity. Conclusions: The oral formulation of ivaltinostat (CG‐750) was generally well tolerated after a single dose. CG‐750 displayed a mean bioavailability of 10.6%. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a heterogenous disease, with prognosis and treatment options depending on Estrogen, Progesterone receptor, and Human Epidermal Growth Factor Receptor-2 (HER-2) status. HER-2 negative, endocrine-independent BC presents a significant clinical challenge with limited treatment options. To date, promising strategies like immune checkpoint inhibitors have not yielded breakthroughs in patient prognosis. Despite being considered archaic, agents derived from natural sources, mainly plants, remain backbone of current treatment. In this context, we critically analyze novel naturally-derived drug candidates, elucidate their intricate mechanisms of action, and evaluate their pre-clinical in vitro and in vivo activity in endocrine-independent HER-2 negative BC. Since pre-clinical research success often does not directly correlate with drug approval, we focus on ongoing clinical trials to uncover current trends. Finally, we demonstrate the potential of combining cutting-edge technologies, such as antibody-drug conjugates or nanomedicine, with naturally-derived agents, offering new opportunities that utilize both traditional cytotoxic agents and new metabolites. [ABSTRACT FROM AUTHOR]

Nanodrugs represent a drug delivery form that brings hope for optimal drug release due to their inherent properties. Special carrier materials give hydrophobic drugs excellent water solubility, and coupled with their small size and delicate design, the uptake of drugs by specific tissues can be enhanced. However, problems such as the rejection of exogenous carriers and the toxicity of the carriers themselves have prevented the clinical translation of nanodrugs. In recent years, the emergence of carrier-free nanodrugs has led to promising results to solve the above problems. In recent years, supramolecular self-assembled nanodrugs formed by non-covalent bonds have been a hot research topic. This review systematically evaluates currently available information on the dynamics of supramolecular self-assembled nanodrug formation and presents the advances in single-component, two-component, and multicomponent self-assembled nanoparticles in tumor therapy. Then it explores how these carrier-free nanodrugs could be functionally optimized based on the perspective of marketed drugs. Last but not least, it analyzes the marketed drugs with supramolecular self-assembly potential. Importantly, these findings could be instrumental in refining the drug delivery systems of novel drugs. [ABSTRACT FROM AUTHOR]

Background: It has become evident in the field of oncology that the outcome of medical treatment is influenced by the combined effect exerted on both cancer- and immune cells. Therefore, we evaluated potential immunological effects of 46 standard anticancer agents and 22 commonly administered concomitant non-cancer drugs. Methods: We utilized a miniaturized in vitro model system comprised of fluorescently labeled human colon and lung cancer cell lines grown as monocultures and co-cultured with activated peripheral blood mononuclear cells (PBMCs). The Bliss Independence Model was then applied to detect antagonism and synergy between the drugs and activated immune cells. Results: Among the standard anticancer agents, tyrosine kinase inhibitors (TKIs) stood out as the top inducers of both antagonism and synergy. Ruxolitinib and dasatinib emerged as the most notably antagonistic substances, exhibiting the lowest Bliss scores, whereas sorafenib was shown to synergize with activated PBMCs. Most concomitant drugs did not induce neither antagonism nor synergy. However, the statins mevastatin and simvastatin were uniquely shown to synergize with activated PBMC at all tested drug concentrations in the colon cancer model. Conclusion: We utilized a miniaturized tumor-immune model to enable time and cost-effective evaluation of a broad panel of drugs in an immuno-oncology setting in vitro. Using this approach, immunomodulatory effects exerted by TKIs and statins were identified. [ABSTRACT FROM AUTHOR]

Vitamin B12 (cyanocobalamin) is an essential nutrient with very low bioavailability. Compared with normal cells, tumor cells show an increased demand for vitamin B12 to support their abnormal proliferation, which is a feature that can be exploited for the tumor-specific delivery of therapeutic and/or diagnostic agents by functionalizing vitamin B12 with suitable metallodrugs and/or luminescent probes. In this context, we report on the design of fluorescent vitamin B12–metal conjugates of the type [FLUO–B12–{M}] in which cyanocobalamin is functionalized at the 5′-site of the ribose unit with a fluorophore (FLUO: rhodamine 6G), whereas the Co(III)–cyano moiety is N-coordinated to a metal-based anticancer scaffold ({M}: Pt(II) substrate bearing enantiopure phenylamino-oxime ligands derived from R- or S-limonene). Two novel fluorescent cyanocobalamin–platinum(II) derivatives and their corresponding non-fluorescent counterparts were successfully generated and fully characterized, including the evaluation of their lipophilicity and luminescent properties. Although they exhibit low antiproliferative activity (IC50 = 40–70 μM), both fluorescent vitamin B12–platinum(II) conjugates showed an enhanced capability to inhibit cell viability compared with the inactive metal precursors and the non-fluorescent vitamin B12–platinum(II) analogues, confirming the beneficial effect of functionalization with the rhodamine 6G scaffold not only for imaging purposes but also with the aim of improving their biological activity. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS2 was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm2, 30 min, 180 J/cm2) confirmed that MoS2 nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS2 (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit—ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS2 + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS2 hydrogels, indicating a combined effect of photothermal and chemotherapy. [ABSTRACT FROM AUTHOR]

This article examines the negative effects of drugs used in cancer chemotherapy and the steps taken to reduce their toxicity. The research was conducted at a hospital with 40 patients undergoing chemotherapy. The data revealed that the majority of patients who experienced adverse drug reactions (ADRs) were women between the ages of 18 and 60. The most common ADRs were anemia and nausea, and only 43% of patients received treatment to alleviate these reactions. The study highlights the significance of identifying and addressing ADRs to enhance the well-being of cancer patients. [Extracted from the article]

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundTamoxifen (TAM) is a widely used drug in patients with gynecomastia and breast cancer. TAM exerts its anticancer effects via its antiestrogenic activities. Unfortunately, TAM has been reported to exert gonadotoxic effects on male testes. Therefore, this study was designed to explore the possible associated mechanisms involved in TAM-induced testicular dysfunction and the possible ameliorative effects of omega-3 fatty acids (O3FA).MethodologyAnimals were randomly divided into control, O3FA, TAM, and TAM + O3FA. All treatment lasted for 28 days.ResultsTAM exposure impaired sperm qualities (count, motility, and normal morphology) and decreased testicular 3β-HSD and 17β-HSD. It was accompanied by a decline in serum testosterone and an increase in estradiol, luteinizing and follicle-stimulating hormones. These observed alterations were associated with an increase in testicular injury markers, oxido-inflammatory response, and mitochondria-mediated apoptosis. These observed alterations were ameliorated by O3FA treatments.ConclusionsO3FA ameliorated TAM-induced testicular dysfunction in male Wistar rats by modulating XO/UA and Nrf2/NF-kb signaling and cytochrome c-mediated apoptosis in TAM-treated rats.

Multiwalled carbon nanotubes (MWCNTs) are at the forefront of nanotechnology-based advancements in cancer therapy, particularly in the field of targeted drug delivery. The nanotubes are characterized by their concentric graphene layers, which give them outstanding structural strength. They can deliver substantial doses of therapeutic agents, potentially reducing treatment frequency and improving patient compliance. MWCNTs’ diminutive size and modifiable surface enable them to have a high drug loading capacity and penetrate biological barriers. As a result of the extensive research on these nanomaterials, they have been studied extensively as synthetic and chemically functionalized molecules, which can be combined with various ligands (such as folic acid, antibodies, peptides, mannose, galactose, polymers) and linkers, and to deliver anticancer drugs, including but not limited to paclitaxel, docetaxel, cisplatin, doxorubicin, tamoxifen, methotrexate, quercetin and others, to cancer cells. This functionalization facilitates selective targeting of cancer cells, as these ligands bind to specific receptors overexpressed in tumor cells. By sparing non-cancerous cells and delivering the therapeutic payload precisely to cancer cells, this therapeutic payload delivery ability reduces chemotherapy systemic toxicity. There is great potential for MWCNTs to be used as targeted delivery systems for drugs. In this review, we discuss techniques for functionalizing and conjugating MWCNTs to drugs using natural and biomacromolecular linkers, which can bind to the cancer cells’ receptors/biomolecules. Using MWCNTs to administer cancer drugs is a transformative approach to cancer treatment that combines nanotechnology and pharmacotherapy. It is an exciting and rich field of research to explore and optimize MWCNTs for drug delivery purposes, which could result in significant benefits for cancer patients.

Globally, cancer is a serious health problem. It is unfortunate that current anti-cancer strategies are insufficiently specific and damage the normal tissues. There’s urgent need for development of new anti-cancer strategies. More recently, increasing attention has been paid to the new application of ferroptosis and nano materials in cancer research. Ferroptosis, a condition characterized by excessive reactive oxygen species-induced lipid peroxidation, as a new programmed cell death mode, exists in the process of a number of diseases, including cancers, neurodegenerative disease, cerebral hemorrhage, liver disease, and renal failure. There is growing evidence that inducing ferroptosis has proven to be an effective strategy against a variety of chemo-resistant cancer cells. Nano-drug delivery system based on nanotechnology provides a highly promising platform with the benefits of precise control of drug release and reduced toxicity and side effects. This paper reviews the latest advances of combination therapy strategies based on biomedical nanotechnology induced ferroptosis for cancer therapeutics. Given the new chances and challenges in this emerging area, we need more attention to the combination of nanotechnology and ferroptosis in the treatment of cancer in the future.

Introduction: This systematic review investigated strategies to mitigate cardiotoxicity induced by anticancer medications, emphasizing exercise and pharmacological interventions. Methods: We systematically reviewed three randomized controlled trials (RCTs), one ATOPE trial, and one retrospective cohort study. Results: Among 448 patients, exercise interventions, particularly in breast cancer patients, demonstrated significant improvements in left ventricular ejection fraction (LVEF) and cardiotoxicity prevention. Pharmacological interventions, including candesartan and carvedilol, have shown potential in reducing early DOX-induced subclinical cardiotoxicity (DISC). The protective efficacy of candesartan in alleviating DISC was greater than carvedilol and the control group. Combination therapy with lisinopril and bisoprolol effectively preserved the LVEF. A retrospective cohort study demonstrated the cardioprotective potential of SGLT-2 inhibitors in reducing cardiovascular events. Conclusion: This systematic review underscores the promise of exercise and pharmacological interventions for preserving cardiac function in cancer patients receiving chemotherapy. These findings have significant implications for enhancing the quality of care for cancer patients.

Cancer is one of the deadliest diseases in the world. Currently, there are various types of anticancer drugs that are used to treat cancer, but they still have various side effects that can interfere with the quality of life of patients. Organometallic complexes (OCOs) are chemical compounds consisting of metal atoms bonded to carbon atoms. OCOs have various potential to be used as anticancer drugs, including their ability to specifically target cancer cells, inhibit cancer cell growth, and reduce the side effects of other anticancer drugs. The mechanism of action of OCOs involves interactions with nucleophilic molecules within the cell, including DNA, RNA, and proteins, as well as the formation of additional platinum products. In this review, we will discuss organometallic compounds that can function as anticancer drugs, such as platinum, ruthenium, iron, carboplatin, and oxaliplatin, which have been shown to be effective in fighting cancer. We will also discuss the mechanism of action of these compounds in cancer cells and the types of cancer cells that can be treated with organometallic compounds.

Human studies have shown the anticancer effects of dietary isothiocyanates (ITCs), but there are some inconsistencies, and more evidence supports that such anticancer effect is from higher doses of ITCs. The inconsistencies found in epidemiological studies may be due to many factors, including the biphasic dose–response (so called hormetic effect) of ITCs, which was found to be more profound under hypoxia conditions. In this comprehensive review, we aim to shed light on the intriguing synergistic interactions between dietary ITCs, focusing on sulforaphane (SFN) and various anticancer drugs. Our exploration is motivated by the potential of these combinations to enhance cancer management strategies. While the anticancer properties of ITCs have been recognized, our review delves deeper into understanding the mechanisms and emphasizing the significance of the hormetic effect of ITCs, characterized by lower doses stimulating both normal cells and cancer cells, whereas higher doses are toxic to cancer cells and inhibit their growth. We have examined a spectrum of studies unraveling the multifaceted interaction and combinational effects of ITCs with anticancer agents. Our analysis reveals the potential of these synergies to augment therapeutic efficacy, mitigate chemoresistance, and minimize toxic effects, thereby opening avenues for therapeutic innovation. The review will provide insights into the underlying mechanisms of action, for example, by spotlighting the pivotal role of Nrf2 and antioxidant enzymes in prevention. Finally, we glimpse ongoing research endeavors and contemplate future directions in this dynamic field. We believe that our work contributes valuable perspectives on nutrition and cancer and holds promise for developing novel and optimized therapeutic strategies.

Summary: Background: High prices of anticancer drugs have raised concerns due to their financial impact on patients and healthcare systems. This study aimed to assess the initial and latest list prices and clinical value of reimbursed anticancer drugs in China, Japan, and South Korea. Methods: We identified anticancer drugs newly approved by the National Medical Products Administration of China from January 2012 to June 2022, and by the Pharmaceuticals and Medical Devices Agency of Japan and the Ministry of Food and Drug Safety of South Korea up until June 2022. We compared initial and latest treatment prices between countries and assessed clinical value using patients’ survival, quality of life (QoL), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Spearman rank correlation coefficients of treatment prices with clinical value for individual countries and employed regression analyses to investigate whether the relationship between prices and clinical value was modified by the country setting. Findings: Our cohort included 91 anticancer drug indications, with 60 listed for reimbursement in China, 91 in Japan, and 87 in South Korea. Median treatment prices were highest in Japan, followed by South Korea, and lowest in China, both for initial prices (US$64082 vs. US$45529 vs. US$19144, p

As the most abundant protein in the blood, albumin binds and transports hydrophilic, hydrophobic, and lipophilic molecules required for the growth and development of cells and tissues. Due to the surface location of charged groups and the inner hydrophobic site, it transports proteins, peptides, amino acids, fatty acids, nutrients, and other biomolecules. It is a multi-domain protein involved in various functions of the blood, including the contribution to oncotic pressure. Because of its unique sequence and structure, albumin can be efficiently utilized to develop drug delivery systems against various diseases, including cancer. As a protein, rich in both negative and positive charges on the surface, it attracts great attention in the drug delivery discipline. Inner hydrophobic sites were proven to be an efficient location for delivering hydrophobic and lipophilic drugs. Albumin binding domains, widely distributed among receptors and matricellular molecules, ease its penetration into cells. A high ratio of cysteine provides stability to the molecule and causes thiol-disulfide interactions, which play an essential role in drug release. In this work, we highlighted several points of albumin nature as a drug-carrying molecule regarding biochemical and physical properties: self-assembling, formation of covalent bonds, formation of in situ albumin corona, etc. Research publications were searched in the NCBI database by various keywords related to sections/subsections to review the related topic. Tens of research works have been dedicated to enhancing the therapeutic efficacy of anticancer drugs using albumin in the last two decades and contributed to clarifying the mechanistic action of albumin. We discussed its mechanisms of action in drug delivery in the first section. In another section, we reviewed the enhanced antitumor/anticancer efficacies of those fabricated DDSs in terms of albumin contribution. The results of in vitro and in vivo experiments were merged into that section consisting of subsections of DDSs of individual anticancer means. Clinical trials of three drugs were reviewed as a separate section. The approaches used to enhance the efficacy of albumin-based DDSs were reviewed in the last section. The final section is devoted to strategies that could significantly improve albumin efficacy in cancer drug delivery.

Abstract Background Medical fraternity are continuously pitching toward the development of novel mechanisms to combat the menace of cancer and to enhance the efficacy of prevailing molecules. During the drug development phase, majority of new molecular entity pose a threat due to hydrophobic nature, that compromises its bioavailability upon administration. These suboptimal accumulation and low drug loading hampers the clinical translation in cancer therapy. Main body of abstract Nanotechnology with valuable advantages create possibilities to accelerate the efficacy of treatment. Compared to matrix-based formulations, drug nanocrystals (NCs) with smaller size, high drug loading, high active targeting, extended circulation, great structural stability, tailored dissolution, and being carrier free have sparked a lot of interest in drug delivery. Many hydrophobic drugs were explored as drug NCs such as—doxorubicin, paclitaxel, campothecin and so on. However, premature leakage and clearance by mononuclear phagocytosis system lead to some great obstacles in the clinical applications of drug NCs. Conclusion In the recent years, strategies leading to surface modification are applied to improve uncontrolled drug release and targeting efficiency to tumor cells. The current review sheds light on various properties of drug nanocrystals, brief insights on its fabricating techniques, approaches for tumor targeting with NCs, and their applications in cancer imaging and therapeutics.

AbstractCancer is a very heterogeneous disease, and uncontrolled cell division is the main characteristic of cancer. Cancerous cells need a high nutrition intake to enable aberrant growth and survival. To do so, cancer cells modify metabolic pathways to produce energy and anabolic precursors and preserve redox balance. Due to the importance of metabolic pathways in tumor growth and malignant transformation, metabolic pathways have also been given promising perspectives for cancer treatment, providing more effective treatment strategies, and target-specific with minimum side effects. Metabolism-based therapeutic nanomaterials for targeted cancer treatment are a promising option. Numerous types of nanoparticles (NPs) are employed in the research and analysis of various cancer therapies. The current review focuses on cutting-edge strategies and current cancer therapy methods based on nanomaterials that target various cancer metabolisms. Additionally, it highlighted the primacy of NPs-based cancer therapies over traditional ones, the challenges, and the future potential.

EGFR is a protein kinase whose aberrant activity is frequently involved in the development of non-small lung cancer (NSCLC) drug resistant forms. The allosteric inhibition of this enzyme is currently one among the most attractive approaches to design and develop anticancer drugs. In a previous study, we reported the identification of a hit compound acting as type III allosteric inhibitor of the L858R/T790M double mutant EGFR. Herein, we report the design, synthesis and in vitro testing of a series of analogues of the previously identified hit with the aim of exploring the structure-activity relationships (SAR) around this scaffold. The performed analyses allowed us to identify two compounds 15 and 18 showing improved inhibition of double mutant EGFR with respect to the original hit, as well as interesting antiproliferative activity against H1975 NSCLC cancer cells expressing double mutant EGFR. The newly discovered compounds represent promising starting points for further hit-to-lead optimisation.

Drug development from medicinal plants constitutes an important strategy for finding natural anticancer therapies. While several plant secondary metabolites with potential antitumor activities have been identified, well-defined mechanisms of action remained uncovered. In fact, studies of medicinal plants have often focused on the genome, transcriptome, and proteome, dismissing the relevance of the metabolome for discovering effective plant-based drugs. Metabolomics has gained huge interest in cancer research as it facilitates the identification of potential anticancer metabolites and uncovers the metabolomic alterations that occur in cancer cells in response to treatment. This holds great promise for investigating the mode of action of target metabolites. Although metabolomics has made significant contributions to drug discovery, research in this area is still ongoing. In this review, we emphasize the significance of plant metabolomics in anticancer research, which continues to be a potential technique for the development of anticancer drugs in spite of all the challenges encountered. As well, we provide insights into the essential elements required for performing effective metabolomics analyses.

The field of oncology has witnessed remarkable progress in personalized cancer therapy. Functional precision medicine has emerged as a promising avenue for achieving superior treatment outcomes by integrating omics profiling and sensitivity testing of patient-derived cancer cells. This review paper provides an in-depth analysis of the evolution of cancer-directed drugs, resistance mechanisms, and the role of functional precision medicine platforms in revolutionizing individualized treatment strategies. Using two-dimensional (2D) and three-dimensional (3D) cell cultures, patient-derived xenograft (PDX) models, and advanced functional assays has significantly improved our understanding of tumor behavior and drug response. This progress will lead to identifying more effective treatments for more patients. Considering the limited eligibility of patients based on a genome-targeted approach for receiving targeted therapy, functional precision medicine provides unprecedented opportunities for customizing medical interventions according to individual patient traits and individual drug responses. This review delineates the current landscape, explores limitations, and presents future perspectives to inspire ongoing advancements in functional precision medicine for personalized cancer therapy.

Although various chemically synthesized materials are essential in medicine, food, and agriculture, they can exert unexpected side effects on the environment and human health by releasing certain toxic chemicals. Therefore, eco-friendly and biocompatible biomaterials based on natural resources are being actively explored. Recently, biosilica derived from diatoms has attracted attention in various biomedical fields, including drug delivery systems (DDS), due to its uniform porous nano-pattern, hierarchical structure, and abundant silanol functional groups. Importantly, the structural characteristics of diatom biosilica improve the solubility of poorly soluble substances and enable sustained release of loaded drugs. Additionally, diatom biosilica predominantly comprises SiO2, has high biocompatibility, and can easily hybridize with other DDS platforms, including hydrogels and cationic DDS, owing to its strong negative charge and abundant silanol groups. This review explores the potential applications of various diatom biosilica-based DDS in various biomedical fields, with a particular focus on hybrid DDS utilizing them.

Breast cancer has the highest incidence rate among all malignancies worldwide. Its high mortality is mainly related to the occurrence of multidrug resistance, which significantly limits therapeutic options. In this regard, there is an urgent need to develop compounds that would overcome this phenomenon. There are few reports in the literature that selenium compounds can modulate the activity of P-glycoprotein (MDR1). Therefore, we performed in silico studies and evaluated the effects of the novel selenoesters EDAG-1 and EDAG-8 on BCRP, MDR1, and MRP1 resistance proteins in MCF-7 and MDA-MB-231 breast cancer cells. The cytometric analysis showed that the tested compounds (especially EDAG-8) are inhibitors of BCRP, MDR1, and MRP1 efflux pumps (more potent than the reference compounds—novobiocin, verapamil, and MK-571). An in silico study correlates with these results, suggesting that the compound with the lowest binding energy to these transporters (EDAG-8) has a more favorable spatial structure affecting its anticancer activity, making it a promising candidate in the development of a novel anticancer agent for future breast cancer therapy.

In recent years, considerable achievements have been made in pediatric oncology with the innovation and development of antitumor drugs. However, compared to adults, children as a special group have not yet matured fully in terms of liver and kidney function. Moreover, pediatric patients are prone to more adverse drug reactions (ADRs) from the accumulation of antineoplastic drugs due to their smaller body size and larger body surface area. Chemotherapy-related ADRs have become a non-negligible factor that affects cancer remission. To date, studies on ADRs in pediatric cancer patients have emerged internationally, but few systematic summaries are available. Here, we reviewed the various systemic ADRs associated with antitumor drugs in children and adolescent patients, as well as the advances in strategies to cope with ADRs, which consisted of neurotoxicity, hematological toxicity, cardiotoxicity, ADRs of the respiratory system and gastrointestinal system and urinary system, ADRs of the skin and its adnexa, allergic reactions, and other ADRs. For clinicians and researchers, understanding the causes, symptoms, and coping strategies for ADRs caused by anticancer treatments will undoubtedly benefit more children. [ABSTRACT FROM AUTHOR]

Histone deacetylases (HDACs) are promising targets for the design of anticancer drugs. HDAC6 is of particular interest since it is a cytoplasmic HDAC regulating the acetylation state of cancer-relevant cytoplasmic proteins such as tubulin, Hsp90, p53, and others. HDAC6 also influences the immune system, and the combination of HDAC6 inhibitors with immune therapy showed promising anticancer results. In addition, the design of new HDAC6 inhibitors led to potent anticancer drugs with immunomodulatory activities. This review describes the current state of play, and the recent developments in the research on the interactions of HDAC6 inhibitors with the immune system, and the development of new HDAC6 inhibitors with immunomodulatory activities to improve the therapy options for cancer patients. • HDAC6 inhibitors with immunomodulatory activities augment chemotherapy and immune therapy. • New HDAC6 inhibitors showed improved activity and toxicity profiles. • Early clinical trials of HDAC6 inhibitors in combination with immunomodulatory drugs are promising. [ABSTRACT FROM AUTHOR]

The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including VEGF-A, VEGF-C, HIF-1a, ANGPT2, and NOS3, were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the VEGF-A (rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in ADH1A (rs6811453), ADH6 (rs10008281), SULT1A2/CCDC101 (rs11401), CYP26A1 (rs7905939), DPYD (rs2297595 and rs1801265), FMO2 (rs2020863), and SLC22A14 (rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs), commonly referred to as host defense peptides, are found in a wide range of organisms, including bacteria, plants, and both vertebrate and invertebrate animals. They function as an initial defense mechanism against pathogenic microorganisms, modulate immune responses, and in specific instances, confer protection against the onset of cancer. Pleurocidin (Ple) is a linear antimicrobial peptide with amphipathic a-helical conformation, isolated originally from the winter flounder (Pleuronectes americanus), notable for its wide-ranging effectiveness against both bacteria and fungi. While the majority of research on pleurocidin's biological characteristics has primarily focused on deciphering its mechanisms of interaction with the biological membranes of pathogenic bacteria and host cells, as well as investigating its modes of killing activities, there is a growing body of evidence suggesting that pleurocidin and pleurocidin-derived analogs might be effectively employed as anti-cancer agents against breast carcinoma and leukemia due to their potent cytotoxic properties and selectivity towards cancer cells. Notably, some characteristics of pleurocidin observed in microbiological investigations of this compound could be effectively applied in examining the anti-cancer capabilities of Ple-like derivatives. This review provides a comprehensive overview of the literature on the biological activities of pleurocidin, pleurocidin-derived peptides, pleurocidin-containing hybrid peptides, and nanosystems. The primary emphasis is on elucidating the range of activities exhibited by these compounds, evaluating their potential therapeutic applications, assessing their safety profile, and identifying any limits observed thus far. This paper will also discuss potential areas for further investigation into the anti-cancer effects of Ple and its derivatives, drawing insights from microbiological research. [ABSTRACT FROM AUTHOR]

Two novel cyclometallated iridium(III) complexes have been prepared with one bidentate or two monodentate imidazole-based ligands, 1 and 2, respectively. The complexes showed intense emission with long lifetimes of the excited state. Femtosecond transient absorption experiments established the nature of the lowest excited state as 3IL state. Singlet oxygen generation with good yields (40% for 1 and 82% for 2) was established by detecting 1O2 directly, through its emission at 1270 nm. Photostability studies were also performed to assess the viability of the complexes as photosensitizers (PS) for photodynamic therapy (PDT). Complex 1 was selected as a good candidate to investigate light-activated killing of cells, whilst complex 2 was found to be toxic in the dark and unstable under light. Complex 1 demonstrated high phototoxicity indexes (PI) in the visible region, PI > 250 after irradiation at 405 nm and PI > 150 at 455 nm, in EJ bladder cancer cells. [ABSTRACT FROM AUTHOR]

The use of platinum-based anticancer drugs, such as cisplatin, oxaliplatin, and carboplatin, is a common frontline option in cancer management, but they have debilitating side effects and can lead to drug resistance. Combination therapy with other chemotherapeutic agents, such as capecitabine and gemcitabine, has been explored. One approach to overcome these limitations is the modification of traditional Pt(II) drugs to obtain new molecules with an improved pharmacological profile, such as Pt(IV) prodrugs. The design, synthesis, and characterization of two novel Pt(IV) prodrugs based on oxaliplatin bearing the anticancer drugs gemcitabine or capecitabine in the axial positions have been reported. These complexes were able to dissociate into their constituents to promote cell death and induce apoptosis and cell cycle blockade in a representative colorectal cancer cell model. Specifically, the complex bearing gemcitabine resulted in being the most active on the HCT116 colorectal cancer cell line with an IC50 value of 0.49 ± 0.04. A pilot study on the encapsulation of these complexes in biocompatible PLGA-PEG nanoparticles is also included to confirm the retention of the pharmacological properties and cellular drug uptake, opening up to the possible delivery of the studied complexes through their nanoformulation. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a rare progressive motor neuron disease that, due to its high complexity, still lacks effective treatments. Development of a new drug is a highly costly and time-consuming process, and the repositioning of approved drugs can represent an efficient strategy to provide therapeutic opportunities. This is particularly true for rare diseases, which are characterised by small patient populations and therefore attract little commercial interest. Based on the overlap between the biological background of cancer and neurodegeneration, the repurposing of antineoplastic drugs for ALS has been suggested. The objective of this narrative review was to summarise the current experimental evidence on the use of approved anticancer drugs in ALS. Specifically, anticancer drugs belonging to different classes were found to act on mechanisms involved in the ALS pathogenesis, and some of them proved to exert beneficial effects in ALS models. However, additional studies are necessary to confirm the real therapeutic potential of anticancer drugs for repositioning in ALS treatment. [ABSTRACT FROM AUTHOR]

Cancer chemotherapy has been shifted from conventional cytotoxic drug therapy to selective and target-specific therapy after the findings about DNA changes and proteins that are responsible for cancer. A large number of newer drugs were discovered as targeted therapy for particular types of neoplastic disease. The initial discovery includes the development of the first in the category, imatinib, a Bcr-Abl tyrosine kinase inhibitor (TKI) for the treatment of chronic myelocytic leukemia in 2001. But the joy did not last for long as the drug developed a point mutation within the ABL1 kinase domain of BCR-ABL1, which subsequently led to the discovery of many other TKIs. Resistance was observed for newer TKIs a few years after their launching, but the use of TKIs in life-threatening cancer therapy is considered as far better compared with the risks of disease because of its target specificity and hence less toxicity. In search of a better anticancer agent, the physiochemical properties of the lead molecule have been modified for its efficacy toward disease and delay in the development of resistance. Deuteration in the drug molecule is one of such modifications that alter the pharmacokinetic properties, generally its metabolism, as compared with its pharmacodynamic effects. Precision deuteration in many anticancer drugs has been carried out to search for better drugs for cancer. In this review, the majority of anticancer drugs and molecules for which deuteration was applied to get better anticancer molecules were discussed. This review will provide a complete guide about the benefits of deuteration in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Herein, we report the synthesis of a series of nine novel cationic triazole‐based complexes C1–C9 and their anticancer assays against cervical cancer cells (Hela), kidney cancer cells (HEK293), lung cancer cells (A549), and leukemia cells (MT4). The complexes have the formula [MCl(Ar)L]+X−, where M is a platinum group metal‐based cation (RuII, OsII, RhIII, or IrIII), Ar is Cp* for Rh and Ir and p‐cymene for Ru and Os, L is the N∧N ${N^ \wedge N}$ ‐chelating ligands 1‐benzyl‐4‐(aminomethyl)‐1H‐1,2,3‐triazole (L1) and 1‐picolyl‐4‐phenyl‐1H‐1,2,3‐triazole (L2), and X− is Cl−, BF4−, or BPh4−. The reaction of ligands L1 and L2 with [Ru(p‐cymene)Cl2]2, [Os(p‐cymene)Cl2]2, [Rh(Cp*)Cl2]2, and [Ir(Cp*)Cl2]2 produced the nine cationic complexes (C1–C9) cumulatively. Normal kidney cell lines (BHK21) were included in the assays to assess the selectivity aspect of these complexes to cancer cells. In general, all the compounds displayed low cytotoxicity except for the ruthenium(II) complex C7 (with BPh4− as the counterion), which showed good activity against all the cancer cell lines (EC50 values as low as 9±1.8 μM. Complex C1 with EC50=16±0.5 μM against MT4 gave the highest selectivity towards cancer cells. C7 was also shown to interact with L‐histidine (L‐His), NADH, bovine serum album (BSA) and guanosine 5'‐monophosphate (5'‐GMP). Due to the observed non‐toxicity of most of the complexes against normal cells, selectivity against specific cancer cells, and interaction with imidazole containing biomolecules, this class of complexes may serve as templates in drug development for targeted therapeutics. [ABSTRACT FROM AUTHOR]

Background: Medical fraternity are continuously pitching toward the development of novel mechanisms to combat the menace of cancer and to enhance the efficacy of prevailing molecules. During the drug development phase, majority of new molecular entity pose a threat due to hydrophobic nature, that compromises its bioavailability upon administration. These suboptimal accumulation and low drug loading hampers the clinical translation in cancer therapy. Nanotechnology with valuable advantages create possibilities to accelerate the efficacy of treatment. Compared to matrix-based formulations, drug nanocrystals (NCs) with smaller size, high drug loading, high active targeting, extended circulation, great structural stability, tailored dissolution, and being carrier free have sparked a lot of interest in drug delivery. Many hydrophobic drugs were explored as drug NCs such as—doxorubicin, paclitaxel, campothecin and so on. However, premature leakage and clearance by mononuclear phagocytosis system lead to some great obstacles in the clinical applications of drug NCs. Conclusion: In the recent years, strategies leading to surface modification are applied to improve uncontrolled drug release and targeting efficiency to tumor cells. The current review sheds light on various properties of drug nanocrystals, brief insights on its fabricating techniques, approaches for tumor targeting with NCs, and their applications in cancer imaging and therapeutics. [ABSTRACT FROM AUTHOR]

Objective: The lack of anticancer drugs for curative and supportive purposes is the critical reason for the low survival rate in low-and-middle-income countries. This study aims to analyze whether the National Essential Medicines List (NEML) and Registered Essential Medicines List (REML) are in concordance with the World Health Organization (WHO) Essential Medicines List (EML) and whether the formularies prevalent in the country are parallel to each other and to the NEML. Method: An observational study design was used in which antineoplastic drugs from the 2021 NEML and REML were compared with 2021 WHO EML to evaluate their availability in Pakistan. Market access was determined. Moreover, the formularies of six different hospital types were compared with each other and with the NEML, and REML to estimate the availability within hospitals. Results: There were 66 anticancer drugs in 2021 WHO EML and all were found in Pakistan's 2021 NEML but only 48 drugs (73%) were found in the REML. Hydroxycarbamide and dasatinib were two registered drugs absent in all hospitals' formularies. The market access for anticancer medicines was 73% (48 of 66). Semigovernment hospital (86%) has the highest availability, followed by the government hospital (80%). All the hospitals have unregistered drugs including bortezomib, lenalidomide, and mesna. Conclusion: Pakistan's NEML adopts WHO EML abruptly but all medicines are not registered. The hospitals are trying their best to increase availability but optimum drug regulations to revise NEML based on the country's requirements and emphasizing registration of anticancer medicines are needed to improve the country's availability of antineoplastic agents. [ABSTRACT FROM AUTHOR]

Combination therapy has exhibited substantial potential compared to monotherapy. However, due to the explosive growth in the number of cancer drugs, the screening of synergistic drug combinations has become both expensive and time-consuming. Synergistic drug combinations refer to the concurrent use of two or more drugs to enhance treatment efficacy. Currently, numerous computational methods have been developed to predict the synergistic effects of anticancer drugs. However, there has been insufficient exploration of how to mine drug and cell line data at different granularity levels for predicting synergistic anticancer drug combinations. Therefore, this study proposes a granularity-level information fusion strategy based on the hypergraph transformer, named HypertranSynergy, to predict synergistic effects of anticancer drugs. HypertranSynergy introduces synergistic connections between cancer cell lines and drug combinations using hypergraph. Then, the Coarse-grained Information Extraction (CIE) module merges the hypergraph with a transformer for node embeddings. In the CIE module, Contranorm is a normalization layer that mitigates over-smoothing, while Gaussian noise addresses local information gaps. Additionally, the Fine-grained Information Extraction (FIE) module assesses fine-grained information's impact on predictions by employing similarity-aware matrices from drug/cell line features. Both CIE and FIE modules are integrated into HypertranSynergy. In addition, HypertranSynergy achieved the AUC of 0.93 |${\pm }$| 0.01 and the AUPR of 0.69 |${\pm }$| 0.02 in 5-fold cross-validation of classification task, and the RMSE of 13.77 |${\pm }$| 0.07 and the PCC of 0.81 |${\pm }$| 0.02 in 5-fold cross-validation of regression task. These results are better than most of the state-of-the-art models. [ABSTRACT FROM AUTHOR]

Catharanthus roseus leaves produce a range of monoterpenoid indole alkaloids (MIAs) that include low levels of the anticancer drugs vinblastine and vincristine. The MIA pathway displays a complex architecture spanning different subcellular and cell type localizations, and is under complex regulation. As a result, the development of strategies to increase the levels of the anticancer MIAs has remained elusive. The pathway involves mesophyll specialized idioblasts where the late unsolved biosynthetic steps are thought to occur. Here, protoplasts of C. roseus leaf idioblasts were isolated by fluorescence-activated cell sorting, and their differential alkaloid and transcriptomic profiles were characterized. This involved the assembly of an improved C. roseus transcriptome from short- and long-read data, IDIO+. It was observed that C. roseus mesophyll idioblasts possess a distinctive transcriptomic profile associated with protection against biotic and abiotic stresses, and indicative that this cell type is a carbon sink, in contrast to surrounding mesophyll cells. Moreover, it is shown that idioblasts are a hotspot of alkaloid accumulation, suggesting that their transcriptome may hold the key to the in-depth understanding of the MIA pathway and the success of strategies leading to higher levels of the anticancer drugs. [ABSTRACT FROM AUTHOR]

Phase I clinical trials for testing the combination of anticancer drugs (combination trials) generally start after the tolerability of each drug is evaluated in phase I clinical trials for monotherapy (single-agent trials). In either trial, one of the crucial objectives is to identify the maximum tolerated dose (or dose combination). Several methods to incorporate data from single-agent trials (SA historical data) into subsequent combination trials have been proposed. However, the effect of using SA historical data under the presence of heterogeneity in data between single-agent and combination trials has not been discussed sufficiently. In this study, we examined the relationships among the presence and absence of heterogeneity, the amount of SA historical data incorporated, and the performance of dose-finding designs (e.g., the percentages of correct selection of maximum tolerated dose combination) by conducting an extensive simulation study with 100,000 random toxicity scenarios. In this evaluation, we used a dose-finding design based on a copula-based model that could easily leverage SA historical data. Although our simulations showed that incorporating SA historical data under homogeneity between SA historical and the current data is beneficial, we found advantages in incorporating heterogeneous data, provided heterogeneity is not extremely large. [ABSTRACT FROM AUTHOR]

Mitochondrial toxicity has been shown to contribute to a variety of organ toxicities such as, brain, heart, kidney, and liver. Ifosfamide (IFO) as an anticancer drug, is associated with increased risk of neurotoxicity, cardiotoxicity nephrotoxicity, hepatotoxicity, and hemorrhagic cystitis. The aim of this study was to evaluate the direct effect of IFO on isolated mitochondria obtained from the rat brain, heart, kidney, and liver. Mitochondria were isolated with mechanical lysis and differential centrifugation from different organs and treated with various concentrations of IFO. Using biochemical and flowcytometry assays, we evaluated mitochondrial succinate dehydrogenase (SDH) activity, mitochondrial swelling, lipid peroxidation, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP). Our data showed that IFO did not cause deleterious alterations in mitochondrial functions, mitochondrial swelling, lipid peroxidation ROS formation, and MMP collapse in mitochondria isolated from brain, heart, kidney, and liver. Altogether, the data showed that IFO is not directly toxic in mitochondria isolated from brain, heart, kidney, and liver. This study proved that mitochondria alone does not play the main role in the toxicity of IFO, and suggests to reduce the toxicity of this drug, other pathways resulting in the production of toxic metabolites should be considered. [ABSTRACT FROM AUTHOR]

Metal complexes, which, under physiologic conditions, show redox properties and are able to bind to DNA, are great tools to cleave the DNA chain. This aspect is of great importance for their use as antineoplastic drugs. We synthesized ligands derived from short-chain amino acids and from salicylaldehyde. The prepared ligands of the type of reduced Schiff bases were subsequently used for the preparation of copper(II) complexes. The aim of the study was in vitro testing of copper(II) complexes, where it was confirmed that they are capable of cleaving DNA. Their cytotoxic activity was also confirmed by the resazurin redox method on Saccharomyces cerevisiae based on preserved healthy mitochondrial function. [ABSTRACT FROM AUTHOR]