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Kavaratamide A (1), a new linear lipodepsipeptide possessing an unusual isopropyl-O-methylpyrrolinone moiety, was discovered from the tropical marine filamentous cyanobacterium Moorena bouillonii collected from Kavaratti, India. A comparative chemogeographic analysis of M. bouillonii collected from six different geographical regions led to the prioritized isolation of this metabolite from India as distinctive among our data sets. AI-based structure annotation tools, including SMART 2.1 and DeepSAT, accelerated the structure elucidation by providing useful structural clues, and the full planar structure was elucidated based on comprehensive HRMS, MS/MS fragmentation, and NMR data interpretation. Subsequently, the absolute configuration of 1 was determined using advanced Marfey's analysis, modified Mosher's ester derivatization, and chiral-phase HPLC. The structures of kavaratamides B (2) and C (3) are proposed based on a detailed analysis of their MS/MS fragmentations. The biological activity of kavaratamide A was also investigated and found to show moderate cytotoxicity to the D283-medullablastoma cell line.

ABSTRACT Photodynamic therapy (PDT) is a promising treatment for cancer. At present, the development of photosensitizers has become a hot spot for research at home and abroad. In this study, 20 porphyrin‐butylphenol compounds were synthesized, and the structures of the target compounds were analyzed by means of 1H NMR, IR, mass spectrometry, and other analytical methods. The quantum yield of the target compound as a photosensitizer for the production of singlet oxygen was determined by using a DPBF reactive oxygen probe (1,3‐diphenylisobenzofuran). The anticancer activity of the synthesized target compounds was studied using HepG2 cells and A549 cells. The results of the singlet oxygen experiments showed that the Zn metal chelated compound had better singlet oxygen production than the free‐base porphyrin. The cellular activity assays showed that the metal‐chelated compounds exhibited better in vitro antitumor activity. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) is considered to be one of the most comprehensive and influential form of traditional medicine. It plays an important role in clinical treatment and adjuvant therapy for cancer. However, the complex composition of TCM presents challenges to the comprehensive and systematic understanding of its antitumor mechanisms, which hinders further development of TCM with antitumor effects. Omics technologies can immensely help in elucidating the mechanism of action of drugs. They utilize high-throughput sequencing and detection techniques to provide deeper insights into biological systems, revealing the intricate mechanisms through which TCM combats tumors. Multi-omics approaches can be used to elucidate the interrelationships among different omics layers by integrating data from various omics disciplines. By analyzing a large amount of data, these approaches further unravel the complex network of mechanisms underlying the antitumor effects of TCM and explain the mutual regulations across different molecular levels. In this study, we presented a comprehensive overview of the recent progress in single-omics and multi-omics research focused on elucidating the mechanisms underlying the antitumor effects of TCM. We discussed the significance of omics technologies in advancing research on the antitumor properties of TCM and also provided novel research perspectives and methodologies for further advancing this research field. [ABSTRACT FROM AUTHOR]

In the following study, a series of new lupeol-3-carbamate derivatives were synthesized, and the structures of all the newly derived compounds were characterized. The new compounds were screened to determine their anti-proliferative activity against human lung cancer cell line A549, human liver cancer cell line HepG2, and human breast cancer cell line MCF-7. Most of the compounds were found to show better anti-proliferative activity in vitro than lupeol. Among them, obvious anti-proliferation activity (IC50 = 5.39~9.43 μM) was exhibited by compound 3i against all three tumor cell lines. In addition, a salt reaction was performed on compound 3k (IC50 = 13.98 μM) and it was observed that the anti-proliferative activity and water solubility of compound 3k·CH3I (IC50 = 3.13 μM), were significantly enhanced subsequent to the salt formation process. The preliminary mechanistic studies demonstrated that apoptosis in HepG2 cells was induced by compound 3k·CH3I through the inhibition of the PI3K/AKT/mTOR pathway. In conclusion, a series of new lupeol-3-carbamate derivatives were synthesized via the structural modification of the C-3 site of lupeol, thus laying a theoretical foundation for the design of this new anticancer drug. [ABSTRACT FROM AUTHOR]

• The aqueous extract of Annona muricata leaves contains high levels of flavonoids and polyphenols. • A remarkable reduction in tumor size was discovered using a mouse model of mastocytoma in Dba/2 mice. • The aqueous extract of Annona muricata has anti-tumor properties. • The in vivo study demonstrated a correlation between the reduction of oxidative stress and the anti-tumor properties following the treatment of Dba/2 mice with the aqueous extract of Annona muricata orally. The medicinal plant Annona muricata of the Annonaceae family, also called Graviola, native to the Andean highlands of Peru and Ecuador but also widespread in Chile, California, Florida, southern Africa and various Mediterranean countries, has various beneficial properties for health and has been the subject of several studies for its anti-tumor activity. In this work, a phytochemical analysis of the aqueous extract of Annona muricata by using HPLC technique to evaluate the content of total polyphenols, flavonoids and tannins, was performed. In addition, for the first time, an evaluation of the effect of the aqueous extract on a Dba/2 transgenic mouse model carrying a P815 tumor, was established. Following the administration of oral doses of 250 and 500 mg/kg for 30 days, a decrease in the volume and weight of the tumors was detected. Furthermore, a correlation between the reduction of oxidative stress and the anticancer properties of Annona muricata, was demonstrated. In conclusion , the aqueous extract of Annona muricata may provide a new therapeutic approach to manage unwanted growth of mastocytoma (P815 tumor) by targeting oxidative stress. [ABSTRACT FROM AUTHOR]

Metal complexes based on N‐heterocyclic carbene (NHC) ligands have emerged as promising broad‐spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies on cytotoxic metal–NHC complexes have yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer complexes are not fully understood, some potential targets and modes of action have been identified. However, a comprehensive review of their biological mechanisms is currently absent. In general, apoptosis caused by metal–NHCs is common in tumor cells. They can cause a series of changes after entering cells, such as mitochondrial membrane potential (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, and caspase activation, ultimately leading to apoptosis. Therefore, a detailed understanding of the influence of metal–NHCs on cancer cell apoptosis is crucial. In this review, we provide a comprehensive summary of recent advances in metal–NHC complexes that trigger apoptotic cell death via different apoptosis‐related targets or signaling pathways, including B‐cell lymphoma 2 (Bcl‐2 family), p53, cyt c, ER stress, lysosome damage, thioredoxin reductase (TrxR) inhibition, and so forth. We also discuss the challenges, limitations, and future directions of metal–NHC complexes to elucidate their emerging application in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Cancer cells with their distinct energy supply and metabolic patterns offer unique opportunities for targeted therapy development. This study presents pH/ROS dual-responsive enzyme-carrying nanoparticles for efficient starvation and oxidative therapy in cancer treatment. The nanoparticles, composed of zeolitic imidazolate framework-8 (ZIF-8), glucose oxidase (GOx), and hyaluronic acid (HA), were designed to leverage the unique metabolic characteristics of cancer cells. GOx was covalently modified onto HA to create HA-GOx, demonstrating enhanced enzymatic activity and thermal stability compared with free GOx. The nanoparticles ZIF@HAgel-GOx were then synthesized by adsorbing HA-GOx onto ZIF-8 and crosslinking with a ROS-sensitive crosslinker, acetone-[bis-(2-amino-ethyl)-dithioacetal] (TK). The enzymatic properties of ZIF@HAgel-GOx in solution and in cells were comparable to those of free GOx, and both could consume glucose to catalyze the reaction. The produced H2O2 could decrosslink the gel layer of ZIF@HAgel-GOx, and the produced gluconic acid could degrade the ZIF-8 core, eventually leading to the complete disassembly of ZIF@HAgel-GOx. Cytotoxicity assays revealed that GOx-carrying nanoparticles exhibited superior cytotoxicity to DOX carriers and could effectively eliminate cancer cells with minimal dosage. The findings provide a scientific rationale for the use of enzyme-based therapies in the treatment of various diseases. [ABSTRACT FROM AUTHOR]

Background: cultivated and wild plants are used to treat different ailments. The Astragalus genus is found in temperate and dry climates; thus, it is found in Egypt and the arab world. Astragalus caprinus has a good amount of bioactive chemicals, which may help explain its therapeutic effects in reducing the risk of consequences from disease. Method: The phytochemical investigation of the herb and roots of Astragalus caprinus L. included the analytical characterization for the petroleum ether components by GC/MS, unsaponifiable matter (unsap. fraction), and fatty acids (FAME) investigation by GLC analysis. Main flavonoids were chromatographically isolated from ethyl acetate and n-butanol extracts. In vitro antimicrobial activity has been tested against the Gram-positive bacteria Staphylococcus aureus and Streptococcus mutans for different plant extracts, the Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumonia, the fungus Candida albicans and Aspergillus niger, and the Escherichia coli bacterium. Metabolite cytotoxicity was examined using the MTT assay against HepG-2 (human liver carcinoma) and MCF-7 (breast carcinoma). Results: Identifying the important components of the herb and root petroleum ether extracts was achieved. Using column chromatography, luteolin, cosmosiin (apigenin-7-O-glucoside), and cynaroside (luteolin-7-O-glucoside) were separated and identified using UV, NMR, and Mass Spectroscopy. Root extracts displayed potential antimicrobial activity against most of the tested pathogens. Both extracts (herb and roots) were active against the MCF-7 cell line and HepG-2 cell line with IC50 62.5 ± 0.64 and 72.4 ± 2.3 µg/ml, and 75.9 ± 2.5 and 96.8 ± 4.2 µg/ml, respectively. Conclusion: Astragalus caprinus seems to be a promising source of bioactive compounds that could potentially aid in preventing disease complications and address common health issues in developing countries. Moreover, the various parts of this plant could be utilized as natural raw materials for producing health-boosting products that could address common health issues in developing countries. [ABSTRACT FROM AUTHOR]

This study investigates organotin (IV) complexes derived from the recently synthesized quinazoline Schiff base ligand (L). The research involves synthesizing and characterizing these complexes, including elemental analysis, UV–visible, FT‐IR, mass spectra, and conductometric measurements. Advanced studies such as density functional theory (DFT) are employed to gain insights into the stable electronic configuration. Specifically, the study explores the proposed geometry, revealing a distorted octahedral structure for the complexes. The findings contribute as critical molecular characteristics of these newly synthesized complexes, paving the way for potential applications in diverse fields, including medicinal chemistry. Through an investigation into the antimicrobial properties, the efficacy of the synthesized compounds was assessed against a diverse range of bacterial and fungal strains. Remarkably, the complexes demonstrated significant antimicrobial activities, showing potential applications in combating various microbial infections. In an extended exploration of their medical utility, the compounds were examined for their antibiotic properties against Helicobacter pylori. The Schiff base and its metal complexes emerged as promising antibiotics with notable efficacy against H. pylori, suggesting their potential in addressing infections associated with this bacterium. Furthermore, the antitumor potential of the synthesized complexes was investigated, focusing on their impact on MCF‐7 (Breast carcinoma) cells. The organotin (IV) Schiff base complexes in this research showed remarkable efficacy, evidenced by their notably low IC50 values (9, 10, 11 μg/mL) in comparison with cisplatin. In addition to their potent antitumor effects, these complexes exhibited reduced cytotoxicity toward normal cells (VERO cells) compared with cisplatin. The investigation extends to molecular docking, where this approach aims to elucidate their interactions with specific protein structures, including (2JFZ, 1SC7, and 6W41). The primary objective is to clarify the potential properties of these compounds, focusing on their antibiotic efficacy, anti‐H. pylori activity, antitumor potential, and anti‐COVID‐19 properties. [ABSTRACT FROM AUTHOR]

Apigenin, a dietary flavonoid, has gained increasing attention for its potential therapeutic applications in radiation protection and radiosensitization. Ionizing radiation (IR) can harm healthy cells, but as radiotherapy remains crucial in cancer treatment. Owing to the remarkable application of radiotherapy in the treatment of cancers, it is vital to protect healthy cells from radiation hazards while increasing the sensitivity of cancer cells to radiation. This article reviews the current understanding of apigenin's radioprotective and radiosensitive properties with a focuses on the involved signaling pathways and key molecular targets. When exposed to irradiation, apigenin reduces inflammation via cyclooxygenase‐2 inhibition and modulates proapoptotic and antiapoptotic biomarkers. Apigenin's radical scavenging abilities and antioxidant enhancement mitigate oxidative DNA damage. It inhibits radiation‐induced mammalian target of rapamycin activation, vascular endothelial growth factor (VEGF), matrix metalloproteinase‐2 (MMP), and STAT3 expression, while promoting AMPK, autophagy, and apoptosis, suggesting potential in cancer prevention. As a radiosensitizer, apigenin inhibits tumor growth by inducing apoptosis, suppressing VEGF‐C, tumor necrosis factor alpha, and STAT3, reducing MMP‐2/9 activity, and inhibiting cancer cell glucose uptake. Cellular and animal studies support apigenin's radioprotective and anticancer potential, making it a potential candidate for further research. Investigation into apigenin's therapeutic efficacy in diverse cancer types and radiation damage is essential. [ABSTRACT FROM AUTHOR]

Developing of functional foods is a promising strategy to reduce the increasing burden of colorectal cancer worldwide. Fruit pomace, particularly polyphenol and anthocyanin-rich chokeberry and blueberry, is a valuable ingredient for functional foods and nutraceuticals. Our study aimed to evaluate the anti-inflammatory and antiproliferative effects of chokeberry and blueberry pomace extracts on C2BBe1 colorectal carcinoma cells and explore the underlying signaling pathways. We analyzed both pomace extracts for total polyphenols and anthocyanins using Folin-Ciocalteu method and ultra-performance liquid chromatography, while antioxidative activity was assessed via the 2,2-diphenyl-1-picrylhydrazyl radical scavenging method. We evaluated the in vitro anti-inflammatory and antiproliferative effects using trypan blue exclusion, MTT and LDH assays, and assessed protein levels of p-Erk1/2, Akt-1, STAT1, STAT3, occludin, oxidized proteins, and MDA-protein adducts through western blotting, as well as analysis of a 37-plex panel of inflammatory markers. Chokeberry extracts exhibited higher total polyphenol content, anthocyanin levels, and antioxidative activity compared to blueberry extracts, however, blueberry extracts effects on cell viability and proliferation in C2BBe1 cells were stronger. Both fruit pomaces induced non-inflammatory cell death characterized by membrane integrity loss, beneficial in cancer therapy. Our data suggests chokeberry's cytotoxicity may be mediated by Erk signaling and Akt-1 inhibition, while blueberry uniquely decreased occludin levels. These berries pomaces' potential to mitigate cancer risks and enhance treatment efficacy is promising, warranting further investigation for functional foods development. [ABSTRACT FROM AUTHOR]

This study aimed to biosynthesize zinc oxide nanoparticles (ZnO-NPs) using extracts from various seaweeds, including Ulva lactuca, Ulva intestinalis (Chlorophyta), and Sargassum muticum (Phaeophyceae). The biosynthesized ZnO-NPs were characterized using UV spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and zeta potential analysis. Their antimicrobial activity was assessed using the disk diffusion method, revealing significant efficacy against two bacterial species (Klebsiella pneumoniae and Escherichia coli) and two fungal species (Candida albicans and Aspergillus niger). Additionally, the antioxidant potential of the ZnO-NPs was evaluated based on the total antioxidant capacity, ferric reducing antioxidant power, and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assays. The antioxidant activity of the ZnO-NPs was confirmed using the three antioxidant assays. The ZnO-NPs of U. lactuca recorded the highest antioxidant activity. The cytotoxicity of the ZnO-NPs was tested on different cell lines using the MTT assay. The ZnO-NPs of U. lactuca showed very weak cytotoxic effects on WI 38 (84.98 ± 4.6 µg/mL) and 23, and this result confirmed its safety on normal cells. The ZnO-NPs of U. lactuca showed moderate cytotoxic effects on the HepG-2 (46.66 ± 2.8 µg/mL) and MCF-7 (30.60 ± 2.1 µg/mL) cell lines. In an in vivo study, the ZnO-NPs of U. lactuca showed a decrease in tumor volume, weight, and serum malondialdehyde in experimental mice, while the total antioxidant capacity of the serum was increased. Histopathological changes in ZnO-NPs indicated a reduction in tumor size, a lower number of mitosis divisions, and a rise in apoptosis correlated with the ZnO-NPs of the U. lactuca-treated groups. In conclusion, biosynthesized ZnO-NPs from seaweed showed potent antimicrobial, antioxidant, and antitumor activities, which can be used in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Background: Xanthenes and multi-aryl carbon core containing compounds represent different types of complex and condensed architectures that have impressive wide range of pharmacological, industrial and synthetic applications. Moreover, indoles as building blocks were only found in naturally occurring metabolites with di-aryl carbon cores and in chemically synthesized tri-aryl carbon core containing compounds. Up to date, rare xanthenes with indole bearing multicaryl carbon core have been reported in natural or synthetic products. The underlying mechanism of fluorescein-like arthrocolins with tetra-arylmethyl core were synthesized in an engineered Escherichia coli fed with toluquinol remained unclear. Results: In this study, the Keio collection of single gene knockout strains of 3901 mutants of E. coli BW25113, together with 14 distinct E. coli strains, was applied to explore the origins of endogenous building blocks and the biogenesis for arthrocolin assemblage. Deficiency in bacterial respiratory and aromatic compound degradation genes ubiX, cydB, sucA and ssuE inhibited the mutant growth fed with toluquinol. Metabolomics of the cultures of 3897 mutants revealed that only disruption of tnaA involving in transforming tryptophan to indole, resulted in absence of arthrocolins. Further media optimization, thermal cell killing and cell free analysis indicated that a non-enzyme reaction was involved in the arthrocolin biosynthesis in E. coli. Evaluation of redox potentials and free radicals suggested that an oxygen-mediated free radical reaction was responsible for arthrocolins formation in E. coli. Regulation of oxygen combined with distinct phenol derivatives as inducer, 31 arylmethyl core containing metabolites including 13 new and 8 biological active, were isolated and characterized. Among them, novel arthrocolins with p-hydroxylbenzene ring from tyrosine were achieved through large scale of aerobic fermentation and elucidated x-ray diffraction analysis. Moreover, most of the known compounds in this study were for the first time synthesized in a microbe instead of chemical synthesis. Through feeding the rat with toluquinol after colonizing the intestines of rat with E. coli, arthrocolins also appeared in the rat blood. Conclusion: Our findings provide a mechanistic insight into in vivo synthesis of complex and condensed arthrocolins induced by simple phenols and exploits a quinol based method to generate endogenous aromatic building blocks, as well as a methylidene unit, for the bacteria-facilitated synthesis of multiarylmethanes. [ABSTRACT FROM AUTHOR]

One flavonoid glycoside with demonstrated therapeutic potential for several illnesses, including cancer, is hesperidin. However, because of its limited bioavailability and solubility, it is only marginally absorbed, necessitating a delivery mechanism to reach the intended therapeutic target. Additionally, the cytoskeleton of crustaceans yields chitosan, a naturally occurring biopolymer with mucoadhesive properties that has been used to improve the absorption of advantageous chemical substances like flavonoids. Chitosan/hesperidin nanoparticles (Hes-Nanoparticles) were made using the ion gelation technique. The synthesis of Hes-Nanoparticles was confirmed by several characterization methods, including the swelling test, zeta potential, particle size, FTIR, XRD, TEM, and SEM. DPPH and ABTS were used to demonstrate radical scavenging activity in antioxidant assays of chitosan, hesperidin, and the synthesized Hes-Nanoparticles. In addition, by a viability assay against MDA-MB-231, the anticancer efficacies of chitosan, hesperidin, and the synthesized Hes-Nanoparticles were assessed. Furthermore, annexin-V/PI double staining and the cycle of cell analysis were determined by flow cytometry. The results displayed that Hes-Nanoparticles have higher antioxidant activity than chitosan and hesperidin alone. Also, it has been demonstrated that Hes-Nanoparticles are more effective in early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis than chitosan and hesperidin alone. In conclusion, Hes-Nanoparticles demonstrated more antioxidant and antitumor activities than chitosan and hesperidin alone. Moreover, it has been established that Hes-Nanoparticles, in a highly soluble form, increase activity in contrast to the poorly soluble form of hesperidin alone. [ABSTRACT FROM AUTHOR]

The rising incidence of colorectal cancer (CRC) and gastric cancer (GC) worldwide, coupled with the limited effectiveness of current chemotherapeutic agents, has prioritized the search for new therapeutic options. Natural substances, which often exhibit cytostatic properties, hold significant promise in this area. This review evaluates the anticancer properties of three natural alkaloids—berberine, sanguinarine, and chelerythrine—against CRC and GC. In vivo and in vitro studies have demonstrated that these substances can reduce tumor volume and inhibit the epithelial–mesenchymal transition (EMT) of tumors. At the molecular level, these alkaloids disrupt key signaling pathways in cancer cells, including mTOR, MAPK, EGFR, PI3K/AKT, and NF-κB. Additionally, they exhibit immunomodulatory effects, leading to the induction of programmed cell death through both apoptosis and autophagy. Notably, these substances have shown synergistic effects when combined with classical cytostatic agents such as cyclophosphamide, 5-fluorouracil, cetuximab, and erlotinib. Furthermore, berberine has demonstrated the ability to restore sensitivity in individuals originally resistant to cisplatin GC. Given these findings, natural compounds emerge as a promising option in the chemotherapy of malignant gastrointestinal tumors, particularly in cases with limited treatment options. However, more research is necessary to fully understand their therapeutic potential. [ABSTRACT FROM AUTHOR]

A multifunctional UIO-66-CoO x sonosensitizer, consisting of amorphous UIO-66 loaded with CoO x , is synthesized to simultaneously induce reactive oxygen species generation and GPX4 deactivation, achieving an augmented therapeutic effect via apoptosis-ferroptosis combination therapy. This work highlights the potential of amorphization engineering in enhancing the efficacy of MOF-based sonosensitizer for combined cancer treatments. [Display omitted] The development of efficient and multifunctional sonosensitizers is crucial for enhancing the efficacy of sonodynamic therapy (SDT). Herein, we have successfully constructed a CoO x -loaded amorphous metal-organic framework (MOF) UIO-66 (A-UIO-66-CoO x) sonosensitizer with excellent catalase (CAT)- and glutathione-oxidase (GSH-OXD)-like activities. The A-UIO-66-CoO x exhibits a 2.6-fold increase in singlet oxygen (1O 2) generation under ultrasound (US) exposure compared to crystalline UIO-66 sonosensitizer, which is attributed to its superior charge transfer efficiency and consistent oxygen (O 2) supply. Additionally, the A-UIO-66-CoO x composite reduces the expression of glutathione peroxidase (GPX4) by depleting glutathione (GSH) through Co3+ and Co2+ valence changes. The high levels of highly cytotoxic 1O 2 and deactivation of GPX4 can lead to lethal lipid peroxidation, resulting in concurrent apoptosis and ferroptosis. Both in vitro and vivo tumor models comprehensively confirmed the enhanced SDT antitumor effect using A-UIO-66-CoO x sonosensitizer. Overall, this study emphasizes the possibility of utilizing amorphization engineering to improve the effectiveness of MOFs-based sonosensitizers for combined cancer therapies. [ABSTRACT FROM AUTHOR]

Cancer and oxidative stress are interrelated, with reactive oxygen species (ROS) playing crucial roles in physiological processes and oncogenesis. Excessive ROS levels can induce DNA damage, leading to cancer, and disrupt antioxidant defenses, contributing to diseases like diabetes and cardiovascular disorders. Antioxidant mechanisms include enzymes and small molecules that mitigate ROS damage. However, cancer cells often exploit oxidative conditions to evade apoptosis and promote tumor growth. Antioxidant therapy has shown mixed results, with timing and cancer-type influencing outcomes. Multifunctional drugs targeting multiple pathways offer a promising approach, reducing side effects and improving efficacy. Recent research focuses on sulfur-nitrogen heterocyclic derivatives for their dual antioxidant and anticancer properties, potentially enhancing therapeutic efficacy in oncology. The newly synthesized compounds often do not demonstrate both antioxidant and anticancer properties simultaneously. Heterocyclic rings are typically combined with phenyl groups, where hydroxy substitutions enhance antioxidant activity. On the other hand, electron-withdrawing substituents, particularly at the p-position on the phenyl ring, tend to enhance anticancer activity. [ABSTRACT FROM AUTHOR]

A novel binary compounds as 3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-phenyl-2H benzo [f] indazole-4,9-dione (10) and fused compounds as 2-hydroxy-3-(4-hydroxy-7-methoxy-2-oxo-1,2 dihydroquinolin-3-yl) naphthalene-1,4-dione (7) and naphtha [2,3-b] furan-3,4,9 (2H)-trione (6) based on Lawsone 'that plays as important precursor' was synthesized by reaction with 1,3-diphenyl-1H-pyrazole-4-carbaldehyde and halo-compounds, such as 2-chloro-acetyl chloride or 3-bromo-4-hydroxy-7-methoxyquinolin-2(1H)-one. Spectra and elemental analysis of newly synthesized compounds were investigated. The target molecules were showed easy access to antioxidant (calorimetrical measurement) and antitumor (Ehrlich ascites carcinoma [EAC] cells) activities. Geometrical isomers (enol, Keto conformers, and syn, anti-conformers) were achieved by density functional theory (DFT) that conformed to the spectral analysis of the investigated compounds. [ABSTRACT FROM AUTHOR]

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Chemodynamic therapy (CDT) alone cannot achieve sufficient therapeutic effects due to the excessive glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Developing a novel strategy to improve efficiency is urgently needed. Herein, we prepared a copper silicate nanoplatform (CSNP) derived from colloidal silica. The Cu(II) in CSNP can be reduced to Cu(I), which cascades to induce a subsequent CDT process. Additionally, benefiting from GSH depletion and oxygen (O2) generation under 660 nm laser irradiation, CSNP exhibits both Fenton-like and hypoxia-alleviating activities, contributing to the effective generation of superoxide anion radical (•O2−) and hydroxyl radical (•OH) in the TME. Furthermore, given the suitable band-gap characteristic and excellent photochemical properties, CSNP can also serve as an efficient type-I photosensitizer for photodynamic therapy (PDT). The synergistic CDT/PDT activity of CSNP presents an efficient antitumor effect and biosecurity in both in vitro and in vivo experiments. The development of an all-in-one nanoplatform that integrates Fenton-like and photosensing properties could improve ROS production within tumors. This study highlights the potential of silicate nanomaterials in cancer treatment. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus saponins are the main components of A. membranaceus, a plant widely used in traditional Chinese medicine. Recently, research on the anti-cancer effects of A. membranaceus saponins has received increasing attention. Numerous in vitro and in vivo experimental data indicate that A. membranaceus saponins exhibit significant anti-cancer effects through multiple mechanisms, especially in inhibiting tumor cell proliferation, migration, invasion, and induction of apoptosis, etc. This review compiles relevant studies on the anti-cancer properties of A. membranaceus saponins from various databases over the past two decades. It introduces the mechanism of action of astragalosides, highlighting their therapeutic benefits in the management of cancer. Finally, the urgent problems in the research process are highlighted to promote A. membranaceus saponins as an effective drug against cancer. [ABSTRACT FROM AUTHOR]

Featured Application: The valorization of grape- and tomato-derived extracts and/or bioactives, with anti-inflammatory and antioxidant properties, as bio-functional ingredients of anti-UV sun oils for skin protection. Daily exposure to solar light is not so harmless as previously thought, since UVA and UVB radiation has a significant effect on human health, by inducing skin-related inflammatory manifestations, such as hyperpigmentation, dermatitis, premature aging, erythema, and sunburn, among the most common skin conditions. At the same time, irreversible diseases such as various types of skin cancers, like basal cell carcinoma, melanoma, and squamous cell carcinoma, have begun to increase at dramatic rates, due to inflammatory and oxidative malignant effects of UV radiation exposure. Within this article, the health promoting effects of sunscreen for skin protection and especially of sunscreen enriched with natural antioxidant, anti-inflammatory, anti-allergic, and anti-cancer bio-functional ingredients are thoroughly reviewed. Emphasis is given to bioactives from grape by-products, such as bio-functional phytochemicals like flavonoids, stilbenes, and phenolic acids, as well as to tomato-derived bioactives like lycopene, which act either solely or synergistically and significantly enhance the antioxidant capacity of the composition product, as well as its photo-protection. The promising outcomes from in vitro studies and those reported from in vivo approaches, as well as the mechanisms of the obtained antioxidant, anti-inflammatory, anti-thrombotic, and antitumor action(s) of sunscreens infused with such natural bioactives, are also outlined. Limitations, such as the difficulties in incorporating lipophilic compounds like lycopene and/or amphiphilic phenolics into sunscreen cosmetic formulations, as well as future perspectives on the overall benefits that these compounds give to sunscreens, helping to improve properties such as smell, color, homogeneity, water resistance, and especially the Sun Protection Factor (SPF), are also discussed. [ABSTRACT FROM AUTHOR]

Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9‐dihydroxycoumestans via two‐electrode constant current electrolysis was developed. The application of a two‐phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o‐benzoquinone intermediates from over‐oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1‐targeted antitumor agent. [ABSTRACT FROM AUTHOR]

Introduction: Melanoma is the most aggressive skin cancer, with an increasing occurrence. Despite the recent important improvements due to novel immunotherapy approaches, when late diagnosed, melanoma prognosis is poor due to the metastatic progression and drug-resistance onset. Therefore, there is an urgent need to identify additional therapeutic targets. Melanoma invasive behavior is related to the activity of metalloproteases, able to degrade extracellular matrix leading to tumor dissemination. A recent study suggested that the most potent proteases inhibitor alpha-2-macroglobulin (A2MG) from plasma of hibernating fishes exerts potent antiproliferative effects. Our previous studies showed a significant reduction of A2MG in sera from mice/human melanoma models. Methods: Gene and protein expression studies have been performed by using platforms and databases available online containing expression data from thousands of patients and healthy controls. Results: We carried out an extensive bioinformatics analysis to evaluate the A2MG gene/protein expression on a large cohort of patients affected by many different cancer types, compared to healthy control subjects, and we found a highly significant difference of A2MG expression in 20 out of 31 cancer types (including melanoma) compared to healthy controls. Similar results were also confirmed at the proteomic level using another platform available online. Further, we found that higher A2MG expression is significantly related to overall survival in different cancers including melanoma. Conclusion: Our results strongly suggest A2MG as a novel molecular target in melanoma therapy, as well as in other cancer types. [ABSTRACT FROM AUTHOR]

People have long used plants and plant-derived products to treat a wide range of illnesses. In the present work, Tecoma stans flower was extracted using 90% ethanol. Flavonoids and total phenolic constituents of T. stans flower extract were screened, and polyphenolic compounds were assessed using high-performance liquid chromatography (HPLC). Antidiabetic via a-amylase and a-glucosidase assays, antioxidant via 2,2-diphenyl-1-picryl-hydrazyl-hydrate, ferric reducing antioxidant power, and total antioxidant capacity of T. stans flower extract were assessed. The cytotoxic action for T. stans flower extract was assessed versus WI-38 (human fetal lung fibroblast cells), PC3 (prostate cancer cell line), and SKOV3 (ovarian cancer cell line). The T. stans extract showed promising in vitro anti-diabetic effect with IC50 = 12.08 ± 0.2 µg/mL and 22.83 ± 0.3 µg/mL for a-amylase and a-glucosidase, respectively. Moreover, T. stans showed good in vitro antioxidant action with IC50= 5.36 ± 0.2 µg/mL for DPPH testing, and the best antitumor impact versus PC3 cells with IC50 = 113.27 ± 1.59 µg/mL. Flow cytometric analysis confirmed the role of T. stans in acceleration in apoptosis of PC3 cells through regulation of oxidative enzymes. These results indicate that the derived materials from T. stans flower have multiple medicinal applications. [ABSTRACT FROM AUTHOR]

AbstractSesquilignans PD is a natural phenylpropanoid compound that was isolated from Zanthoxylum nitidum var. tomentosum. In this study, we assessed the antitumor effect of PD on SK-Hep-1 and HepG2 cells and the underlying molecular mechanisms. The results revealed that PD markedly inhibited the proliferation and migration of both liver cancer cells. Moreover, PD induced apoptosis, autophagy, and reactive oxygen species (ROS) production in liver cancer cells. Notably, PD increased the protein levels of p-p38 MAPK and p-ERK1/2 in liver cancer cells. This is the first report on the anticancer effect of PD, which is mediated via increased ROS production and MAPK signaling activation. [ABSTRACT FROM AUTHOR]

This study uses Lilium davidii var. unicolor (Lanzhou lily) polysaccharides extracted from bulbs to prepare nano‐selenium (nano‐Se) polysaccharide (LPS). Here, the study explores the molecular structure characterization, inhibition effects, and mechanisms of action of prepared LPS on A549 lung cancer cells. The LPS structure is characterized using Fourier‐transform infrared spectroscopy (FTIR), UV spectroscopy (UV–vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X‐ray photoelectron spectroscopy (XPS), etc. Results show that selenized polysaccharides bonded through electrostatic adsorption, with an average LPS particle size of 243.75 nm and zeta potential of −38.3 mV, which can be stably preserved at 4 °C for more than 3 months. The in vitro antitumor activity experiment shows that the prepared LPS inhibited A549 cell proliferation while affecting cell migration. Cell cycle analysis shows that apoptosis is promoted by blocking the G1 phase, while during the late apoptosis stage cells accounted for 60%. RNA‐Seq data analysis shows that the main mechanisms of action on A549 cells are to inhibit DNA replication initiation genes, block the cell cycle, and regulate the expression of apoptosis‐related genes and proteins in promoting cell apoptosis. [ABSTRACT FROM AUTHOR]

Elderberry (Sambucus nigra L.) is a widespread deciduous shrub, of which the fruits (elderberries) are used in the food industry to produce different types of dietary supplement products. These berries have been found to show multiple bioactivities, including antidiabetic, anti-infective, antineoplastic, anti-obesity, and antioxidant activities. An elderberry extract product, Sambucol®, has also been used clinically for the treatment of viral respiratory infections. As the major components, phenolic compounds, such as simple phenolic acids, anthocyanins and other flavonoids, and tannins, show promising pharmacological effects that could account for the bioactivities observed for elderberries. Based on these components, salicylic acid and its acetate derivative, aspirin, have long been used for the treatment of different disorders. Dapagliflozin, an FDA-approved antidiabetic drug, has been developed based on the conclusions obtained from a structure–activity relationship study for a simple hydrolyzable tannin, β-pentagalloylglucoside (β-PGG). Thus, the present review focuses on the development of therapeutic agents from elderberries and their small-molecule secondary metabolites. It is hoped that this contribution will support future investigations on elderberries. [ABSTRACT FROM AUTHOR]

The synthesis of novel 5-(2-((1(E/Z),2E)-1,3-disubstitutedallylidene)hydrazinyl)-1,3-dimethyl-4-nitro-1H-pyrazole (4a–k) was attempted via reaction involves a nucleophilic attack which takes place at the carbonyl group of the α,β-unsaturated carbonyls. The transformation proceeds via an effective addition-elimination reaction in the presence of catalytic amount of concentrated H2SO4. The cytotoxicity of synthesized compounds was evaluated against two tumor cell lines, MCF-7 and MDA-MB-231, via MTT assay. The compounds 4a–d showed better toxicity than tamoxifen on MCF-7 cells, ranging from 26.28 to 12.96 µM with 4b having the lowest IC50 among the compounds tested. On the other hand, the compounds have moderate toxicity on MDA-MB-231 with 4c showing the lowest IC50. The docking study suggests that these Schiff bases chalcone scaffolds might facilitate the further development of investigated compounds as anticancer agents. [ABSTRACT FROM AUTHOR]

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Paku gajah (Angiopteris evecta) is one of the largest ferns which has been used empirically by the Dayak tribe of Kalimantan, Indonesia as a traditional medicine to treat various diseases, one of which is tumors. This research aims to determine the potential utilization of A. evecta stem extract as an antitumor by secondary metabolites analysis, toxicity and antitumor assay. The methods used in this study were gradual maceration using three solvents ( n-hexane, ethyl acetate, and methanol), phytochemical screening, toxicity test, antitumor activity assay with the Alamarblue method, Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, and molecular docking analysis. This study indicated that A. evecta stem extract contained secondary metabolites such as flavonoids, saponins, tannins, and steroids. The ethyl acetate and methanol were found as toxic extracts with LC50 130.67 and 314.31 µg/mL, respectively. In line with the toxicity, the antitumor activity of the ethyl acetate extract was the highest with an IC50 of 240.94 µg/mL and phytochemical analysis revealed the presence of violanthin and angiopteroside in the extract. Molecular docking showed that the binding energy and inhibition constants of violanthin and angiopteroside against receptors were higher than standard ligand F82. The interaction between violanthin and the receptor results five hydrogen-bond (H-bond) with Lys920, Cys919, Asp1046, and Leu840, while the angiopteroside produces four H-bonds with Leu836, Leu834, and Arg831. [ABSTRACT FROM AUTHOR]

Polysaccharides from natural sources have an excellent immune function and low toxicity; however, their limitations such as short half‐life and instability limit their sustained pharmacological activity. In this context, the combination of polysaccharides and nanotechnology have been developed to promote the stability and prolong the immune activities of polysaccharides. To synthesize and explore the antitumor effect and immunomodulatory activity of PHP‐AuNPs. Polysaccharides extracted from Pseudostellaria heterophylla were used to synthesize gold nanocomposites (PHP‐AuNPs), and their physicochemical properties and immunoregulatory effect in vitro and in vivo were analyzed. The PHP‐AuNPs were green synthesized with high biosafety. PHP‐AuNPs can activate macrophages in vitro and decrease the tumor weight and volume, whereas they increase the immune organ index in vivo. Besides, PHP‐AuNPs showed a beneficial effect for maintaining the immune balance of CD4+/CD8+ T cells and modulating the release of cytokines such as TNF‐α increase and IL‐10 decrease in mice. All these results suggested that PHP‐AuNPs exhibit a remarkable antitumor effect and stronger immunomodulatory activity than that of free PHP‐1. Research Highlights: The P. heterophylla polysaccharide‐gold nanocomposites (PHP‐AuNPs) were synthesized and physicochemical properties were characterized.The cytotoxicity in vitro and immunomodulatory effects of PHP‐AuNPs on macrophages were analyzed.The immune‐antitumor effects in vivo of PHP‐AuNPs have also been confirmed. [ABSTRACT FROM AUTHOR]

Gastric cancer is an aggressive and multifactorial disease. Helicobacter pylori (H. pylori) is identified as a significant etiological factor in gastric cancer. Although only a fraction of patients infected with H. pylori progresses to gastric cancer, bacterial infection is critical in the pathology and development of this malignancy. The pathogenic mechanisms of this bacterium involve the disruption of the gastric epithelial barrier and the induction of chronic inflammation, oxidative stress, angiogenesis and metastasis. Adherence molecules, virulence (CagA and VacA) and colonization (urease) factors are important in its pathogenicity. On the other hand, resveratrol is a natural polyphenol with anti-inflammatory and antioxidant properties. Resveratrol also inhibits cancer cell proliferation and angiogenesis, suggesting a role as a potential therapeutic agent against cancer. This review explores resveratrol as an alternative cancer treatment, particularly against H. pylori-induced gastric cancer, due to its ability to mitigate the pathogenic effects induced by bacterial infection. Resveratrol has shown efficacy in reducing the proliferation of gastric cancer cells in vitro and in vivo. Moreover, the synergistic effects of resveratrol with chemotherapy and radiotherapy underline its therapeutic potential. However, further research is needed to fully describe its efficacy and safety in treating gastric cancer. [ABSTRACT FROM AUTHOR]

This review presents an overview of the antitumor properties of various platinum(II) complexes of dithiocarbamates. It has been noticed that in several cases the activity is greater than cisplatin, while their toxicity level is low. The monofunctional platinum(II)-dithiocarbamate complexes comprising a labile chloride ligand possess the most effective cytotoxic behavior among the complexes discussed here. The bis(dithiocarbamato) complexes on the other hand show poor anti-proliferative potential. The complexes manifest their antitumor activity through DNA interaction that takes place via covalent bonding, intercalation or electrostatic interaction. The study of apoptotic activity in some cases suggests that these complexes trigger apoptosis, which causes the cell death. The induction of apoptosis is correlated with the generation of reactive oxygen species, the cell cycle arrest and the inhibition of NF-kB activity. The protective effects of dithiocarbamates against the platinum-induced toxicity have been explained. Dithiocarbamates were found to control the side effects of cisplatin and the anticancer activity of cisplatin was significantly improved in the presence of a dithiocarbamate. The study highlights that platinum(II) complexes of dithiocarbamates may be regarded as promising anticancer agents because of their effective cytotoxic properties and their potential to overcome cisplatin resistance. [ABSTRACT FROM AUTHOR]

Abstract Traditional Chinese medicine (TCM) is considered to be one of the most comprehensive and influential form of traditional medicine. It plays an important role in clinical treatment and adjuvant therapy for cancer. However, the complex composition of TCM presents challenges to the comprehensive and systematic understanding of its antitumor mechanisms, which hinders further development of TCM with antitumor effects. Omics technologies can immensely help in elucidating the mechanism of action of drugs. They utilize high-throughput sequencing and detection techniques to provide deeper insights into biological systems, revealing the intricate mechanisms through which TCM combats tumors. Multi-omics approaches can be used to elucidate the interrelationships among different omics layers by integrating data from various omics disciplines. By analyzing a large amount of data, these approaches further unravel the complex network of mechanisms underlying the antitumor effects of TCM and explain the mutual regulations across different molecular levels. In this study, we presented a comprehensive overview of the recent progress in single-omics and multi-omics research focused on elucidating the mechanisms underlying the antitumor effects of TCM. We discussed the significance of omics technologies in advancing research on the antitumor properties of TCM and also provided novel research perspectives and methodologies for further advancing this research field.

Abstract Background Xanthenes and multi-aryl carbon core containing compounds represent different types of complex and condensed architectures that have impressive wide range of pharmacological, industrial and synthetic applications. Moreover, indoles as building blocks were only found in naturally occurring metabolites with di-aryl carbon cores and in chemically synthesized tri-aryl carbon core containing compounds. Up to date, rare xanthenes with indole bearing multicaryl carbon core have been reported in natural or synthetic products. The underlying mechanism of fluorescein-like arthrocolins with tetra-arylmethyl core were synthesized in an engineered Escherichia coli fed with toluquinol remained unclear. Results In this study, the Keio collection of single gene knockout strains of 3901 mutants of E. coli BW25113, together with 14 distinct E. coli strains, was applied to explore the origins of endogenous building blocks and the biogenesis for arthrocolin assemblage. Deficiency in bacterial respiratory and aromatic compound degradation genes ubiX, cydB, sucA and ssuE inhibited the mutant growth fed with toluquinol. Metabolomics of the cultures of 3897 mutants revealed that only disruption of tnaA involving in transforming tryptophan to indole, resulted in absence of arthrocolins. Further media optimization, thermal cell killing and cell free analysis indicated that a non-enzyme reaction was involved in the arthrocolin biosynthesis in E. coli. Evaluation of redox potentials and free radicals suggested that an oxygen-mediated free radical reaction was responsible for arthrocolins formation in E. coli. Regulation of oxygen combined with distinct phenol derivatives as inducer, 31 arylmethyl core containing metabolites including 13 new and 8 biological active, were isolated and characterized. Among them, novel arthrocolins with p-hydroxylbenzene ring from tyrosine were achieved through large scale of aerobic fermentation and elucidated x-ray diffraction analysis. Moreover, most of the known compounds in this study were for the first time synthesized in a microbe instead of chemical synthesis. Through feeding the rat with toluquinol after colonizing the intestines of rat with E. coli, arthrocolins also appeared in the rat blood. Conclusion Our findings provide a mechanistic insight into in vivo synthesis of complex and condensed arthrocolins induced by simple phenols and exploits a quinol based method to generate endogenous aromatic building blocks, as well as a methylidene unit, for the bacteria-facilitated synthesis of multiarylmethanes.

Abstract Background cultivated and wild plants are used to treat different ailments. The Astragalus genus is found in temperate and dry climates; thus, it is found in Egypt and the arab world. Astragalus caprinus has a good amount of bioactive chemicals, which may help explain its therapeutic effects in reducing the risk of consequences from disease. Method The phytochemical investigation of the herb and roots of Astragalus caprinus L. included the analytical characterization for the petroleum ether components by GC/MS, unsaponifiable matter (unsap. fraction), and fatty acids (FAME) investigation by GLC analysis. Main flavonoids were chromatographically isolated from ethyl acetate and n-butanol extracts. In vitro antimicrobial activity has been tested against the Gram-positive bacteria Staphylococcus aureus and Streptococcus mutans for different plant extracts, the Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumonia, the fungus Candida albicans and Aspergillus niger, and the Escherichia coli bacterium. Metabolite cytotoxicity was examined using the MTT assay against HepG-2 (human liver carcinoma) and MCF-7 (breast carcinoma). Results Identifying the important components of the herb and root petroleum ether extracts was achieved. Using column chromatography, luteolin, cosmosiin (apigenin-7-O-glucoside), and cynaroside (luteolin-7-O-glucoside) were separated and identified using UV, NMR, and Mass Spectroscopy. Root extracts displayed potential antimicrobial activity against most of the tested pathogens. Both extracts (herb and roots) were active against the MCF-7 cell line and HepG-2 cell line with IC50 62.5 ± 0.64 and 72.4 ± 2.3 µg/ml, and 75.9 ± 2.5 and 96.8 ± 4.2 µg/ml, respectively. Conclusion Astragalus caprinus seems to be a promising source of bioactive compounds that could potentially aid in preventing disease complications and address common health issues in developing countries. Moreover, the various parts of this plant could be utilized as natural raw materials for producing health-boosting products that could address common health issues in developing countries.

Aathira Sujathan Nair,1 Mahendran Sekar,1 Siew Hua Gan,1 Vinoth Kumarasamy,2 Vetriselvan Subramaniyan,3 Yuan Seng Wu,4 Nur Najihah Izzati Mat Rani,5 Subban Ravi,6 Ling Shing Wong7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 4Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 5Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 6Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 7Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia, Email mahendran.sekar@monash.edu Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email vinoth@ukm.edu.myAbstract: Lawsone, a naturally occurring organic compound also called hennotannic acid, obtained mainly from Lawsonia inermis (Henna). It is a potential drug-like molecule with unique chemical and biological characteristics. Traditionally, henna is used in hair and skin coloring and is also a medicinal herb for various diseases. It is also widely used as a starting material for the synthesis of various drug molecules. In this review, we investigate on the chemistry, biosynthesis, physical and biological properties of lawsone. The results showed that lawsone has potential antioxidant, anti-inflammatory, antimicrobial and antitumor properties. It also induces cell cycle inhibition and programmed cell death in cancer, making it a potential chemotherapeutic agent. Additionally, inhibition of pro-inflammatory cytokine production makes it an essential treatment for inflammatory diseases. Exploration of its biosynthetic pathway can pave the way for its development into targets for new drug development. In future, well-thought-out clinical studies should be made to verify its safety and efficacy. Keywords: lawsone, Lawsonia inermis, henna, antitumor, antioxidant, anti-inflammatory, antimicrobial

Abstract Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer accounting for approximately 85% of lung cancer cases. α-Hederin is a monodesmosidic triterpenoid saponin isolated from the leaves of Hedera helix L. or Nigella sativa and has been extensively studied for its antitumor activity against a variety of tumor cells. It has been suggested that α-Hederin is a potential regulator of autophagy and has high promise for application. However, the specific mechanism and characteristics of α-Hederin in regulating autophagy are not well understood. In this study, we confirmed the potential of α-Hederin application in lung cancer treatment and comprehensively explored the mechanism and characteristics of α-Hederin in regulating autophagy in lung cancer cells. Our results suggest that α-Hederin is an incomplete autophagy inducer that targets mTOR to activate the classical autophagic pathway, inhibits lysosomal acidification without significantly affecting the processes of autophagosome transport, lysosome biogenesis, autophagosome and lysosome fusion, and finally leads to impaired autophagic flux and triggers autophagic damage in NSCLC.

Abstract Antitumor drugs used today have shown significant efficacy and are derived from natural products such as plants. Iso-mukaadial acetate (IMA) has previously been shown to possess anticancer properties by inducing apoptosis. The purpose of this study was to investigate the therapeutic effect of IMA in the breast cancer xenograft mice model. Female athymic nude mice were used and inoculated with breast cancer cells subcutaneously. Untreated group one served as a negative control and positive control group two (cisplatin) was administered intravenously. IMA was administered orally to group three (100 mg/kg) and group four (300 mg/kg). Blood was collected (70 μL) from the tail vein on day zero, day one and day three. Tumor regression was measured every second day and body mass was recorded each day. Estimation of serum parameters for renal indices was examined using a creatinine assay. Histopathological analysis was conducted to evaluate morphological changes of liver, kidney, and spleen tissues before and after compound administration under a fluorescence light microscope. Histopathological analysis of tumors was conducted before and after compound administration. Apoptotic analysis using the TUNEL system was conducted on liver, kidney, and spleen tissues. Tumor shrinkage and reduction in body mass were observed after treatment with IMA. Serum creatinine was slightly elevated after treatment with IMA at a dosage of 100 and 300 mg/kg. Histopathological results of the liver exhibited no changes before and after IMA while the kidney and spleen tissues showed changes in the cellular structure. IMA showed no cytotoxic effect on the tumor cells, and cell proliferation was observed. Apoptotic assay stain with TUNEL showed apoptotic cells in spleen tissue and kidney but no apoptotic cells were observed in liver tissue section treated with IMA. IMA showed clinical toxic signs that resulted in the suffering and death of the mice immediately after IMA administration. Histopathology of tumor cells showed that IMA did not inhibit cell proliferation and no cellular damage was observed. Therefore, based on the results obtained, we cannot make any definitive conclusion on the complete effect of IMA in vivo. IMA is toxic, poorly soluble, and not safe to use in animal studies. The objective of the study was not achieved, and the hypothesis was rejected.

Haiqing Wang,1,* Wentao Bo,1,* Xielin Feng,1 Jinliang Zhang,1 Ge Li,2 Yan Chen3 1Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Emergency, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Chen; Ge Li, Email cyfy1112@163.com; chenyanyaoxuebu@scszlyy.org.cn; 13982129787@qq.comAbstract: Lenvatinib (LVN) is a potentially effective multiple-targeted receptor tyrosine kinase inhibitor approved for treating hepatocellular carcinoma, metastatic renal cell carcinoma and thyroid cancer. Nonetheless, poor pharmacokinetic properties including poor water solubility and rapid metabolic, complex tumor microenvironment, and drug resistance have impeded its satisfactory therapeutic efficacy. This article comprehensively reviews the uses of nanotechnology in LVN to improve antitumor effects. With the characteristic of high modifiability and loading capacity of the nano-drug delivery system, an active targeting approach, controllable drug release, and biomimetic strategies have been devised to deliver LVN to target tumors in sequence, compensating for the lack of passive targeting. The existing applications and advances of LVN in improving therapeutic efficacy include improving longer-term efficiency, achieving higher efficiency, combination therapy, tracking and diagnosing application and reducing toxicity. Therefore, using multiple strategies combined with photothermal, photodynamic, and immunoregulatory therapies potentially overcomes multi-drug resistance, regulates unfavorable tumor microenvironment, and yields higher synergistic antitumor effects. In brief, the nano-LVN delivery system has brought light to the war against cancer while at the same time improving the antitumor effect. More intelligent and multifunctional nanoparticles should be investigated and further converted into clinical applications in the future. Keywords: lenvatinib, nano-drug delivery system, antitumor, side effects, diagnosis

Hanan M Alharbi Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Hanan M Alharbi, Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia, Email hmsharbi@uqu.edu.saAbstract: The burgeoning global mortality rates attributed to cancer have precipitated a critical reassessment of conventional therapeutic modalities, most notably chemotherapy, due to their pronounced adverse effects. This reassessment has instigated a paradigmatic shift towards nanomedicine, with a particular emphasis on the potentialities of biopolymer-assisted drug delivery systems. Biopolymers, distinguished by their impeccable biocompatibility, versatility, and intrinsic biomimetic properties, are rapidly ascending as formidable vectors within the cancer theragnostic arena. This review endeavors to meticulously dissect the avant-garde methodologies central to biopolymer-based nanomedicine, exploring their synthesis, functional mechanisms, and subsequent clinical ramifications. A key focus of this analysis is the pioneering roles and efficacies of lipid-based, polysaccharide, and composite nano-carriers in enhancing drug delivery, notably amplifying the enhanced permeation and retention effect. This examination is further enriched by referencing flagship nano formulations that have received FDA endorsement, thereby underscoring the transformative potential and clinical viability of biopolymer-based nanomedicines. Furthermore, this discourse illuminates groundbreaking advancements in the realm of photodynamic therapy and elucidates the implications of advanced imaging techniques in live models. Conclusively, this review not only synthesizes current research trajectories but also delineates visionary pathways for the integration of cutting-edge biomaterials in cancer treatment. It charts a course for future explorations within the dynamic domain of biopolymer-nanomedicine, thereby contributing to a deeper understanding and enhanced application of these novel therapeutic strategies.Keywords: theragnostic, nanomedicines, antitumor, drug delivery, nanotherapeutic, anticancer, biopolymers

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.

People have long used plants and plant-derived products to treat a wide range of illnesses. In the present work, Tecoma stans flower was extracted using 90% ethanol. Flavonoids and total phenolic constituents of T. stans flower extract were screened, and polyphenolic compounds were assessed using high-performance liquid chromatography (HPLC). Anti-diabetic via α-amylase and α-glucosidase assays, antioxidant via 2,2-diphenyl-1-picryl-hydrazyl-hydrate, ferric reducing antioxidant power, and total antioxidant capacity of T. stans flower extract were assessed. The cytotoxic action for T. stans flower extract was assessed versus WI-38 (human fetal lung fibroblast cells), PC3 (prostate cancer cell line), and SK-OV3 (ovarian cancer cell line). The T. stans extract showed promising in vitro anti-diabetic effect with IC50 = 12.08 ± 0.2 µg/mL and 22.83 ± 0.3 µg/mL for α-amylase and α-glucosidase, respectively. Moreover, T. stans showed good in vitro antioxidant action with IC50= 5.36 ± 0.2 µg/mL for DPPH testing, and the best antitumor impact versus PC3 cells with IC50 = 113.27 ± 1.59 µg/mL. Flow cytometric analysis confirmed the role of T. stans in acceleration in apoptosis of PC3 cells through regulation of oxidative enzymes. These results indicate that the derived materials from T. stans flower have multiple medicinal applications.

We aimed to identify the mechanism of action of the Scutellaria barbata in the treatment of prostate cancer. First, the main active components of Scutellaria barbata for the treatment of prostate cancer were predicted by network pharmacology. Disease-related targets were then retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP); GeneCards: The Human Gene Database; and the Online Catalog of Human Genes and Genetic Disorders (OMIM). Then, we identified intersecting genes between the components and targets. Cytoscape software was then used to construct a “Drug-Ingredient-Disease-Target” network. We also used the STRING platform to perform protein interaction analysis. R software was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Our analysis identified 212 potential targets for Scutellaria barbata in the treatment of prostate cancer; these were closely related to a number of specific pathways, including prostate cancer, the advanced glycation end products and their receptors (AGE-RAGE) signaling pathway in diabetic complications, lipids and atherosclerosis, hepatitis B, fluid shear stress and atherosclerosis, chemical carcinogenesis, receptor activation, Kaposi’s sarcoma-associated herpesvirus infection, and human cytomegalovirus infection. Furthermore, the treatment of prostate cancer with Scutellaria barbata may act via a range of biological processes, including responses to xenobiotic stimuli, lipopolysaccharides and metal ions. Several molecular functions may be involved, including DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and nuclear receptor activity. Our research demonstrates the multi-component, multi-target, multi-pathway, and synergistic characteristics of Scutellaria barbata for the treatment of prostate cancer, and provides theoretical guidelines for further elucidating its mechanism of action.

Abstract Introduction Lung cancer (LC) is the most common solid tumor and is currently considered the primary cause of cancer-related deaths worldwide. In clinical efficacy studies, it was not difficult to find that the combination of SFI and chemotherapy could improve the general condition of patients, reduce the side effects of chemotherapy drugs, and have a cooperative antitumor effect in NSCLC patients. However, whether SFI can be used as a novel antitumor drug is still unknown. Methods First, meta-analysis aimed to explore the efficacy of SFI in NSCLC patients, and SFI was identified by ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS). Cell proliferation, migration, and invasion were explored by Cell Counting Kit-8 (CCK-8), scratch healing, and Transwell assays, respectively. Cell cycle and apoptosis assays were performed by flow cytometry. Transcriptome sequencing analysis was performed in four NSCLC cell lines. Differential expression analysis was used to identify potential targets. Apoptosis-related protein levels were detected by Western blotting assays. The effects of SFI in NSCLC were further investigated by mouse xenografts. Results SFI could markedly improve the chemotherapy efficacy of NSCLC patients. The main active ingredients include flavonoids and terpenoids, which can effectively exert antitumor effects. SFI could not only inhibit tumor cell proliferation and cell migration/invasion but also regulate the cell cycle and promote tumor cell apoptosis. In NSCLC, SFI could enhance the transcription level of the CHOP gene, thereby upregulating the expression of the proapoptotic proteins Bax and caspase 3, and inhibiting the expression of the antiapoptotic protein Bcl-2. SFI hindered the growth of mouse NSCLC xenografts in vivo. Conclusions SFI hindered tumor progression and might promote apoptosis by increasing the expression of Bax, caspase 3 and decreasing the level of Bcl-2 in NSCLC.

Mornaphthoate E (MPE) is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines. In the current project, the first total synthesis of (±)-MPE was achieved in seven steps and 5.6% overall yield. Then the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells, with the levoisomer exerting slightly better potency. The in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse model. Notably, MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic dosage. Mechanistic investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt signaling. In conclusion, our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.

Abstract Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization.

The treatment of tumors in developing countries, especially those with poor medical conditions, remains a significant challenge. Herein, a novel solvent‐exchange strategy to prepare adhesive hydrogels for the concurrent treatment of tumors through synchronous ethanol ablation and local chemotherapy is reported. First, a poly (gallic acid‐lipoic acid) (PGL) ethanol gel is prepared that can undergo solvent exchange with water to form a hydrogel in situ. PGL ethanol gel deposited on the wet tissue can form a hydrogel in situ to effectively repel interfacial water and establish a tight contact between the hydrogel and tissue. Additionally, the functional groups between the hydrogels and tissues can form covalent and non‐covalent bonds, resulting in robust adhesion. Furthermore, this PGL ethanol gel demonstrates exceptional capacity to effectively load antitumor drugs, allowing for controlled and sustained release of the drugs locally and sustainably both in vitro and in vivo. In addition, the PGL ethanol gel can combine ethanol ablation and local chemotherapy to enhance the antitumor efficacy in vitro and in vivo. The PGL ethanol gel‐derived hydrogel shows robust wet bioadhesion, drug loading, sustained release, good biocompatibility and biodegradability, easy preparation and usage, and cost‐effectiveness, which make it a promising bioadhesive for diverse biomedical applications. [ABSTRACT FROM AUTHOR]

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof‐of‐concept, hereby a conventional strategy is presented to prepare donor–acceptor (D–A) structured PTAs through cycloaddition‐retroelectrocyclization (CA–RE) reaction, and the resultant PTAs give high PCE upon near‐infrared (NIR) irradiation. By joint experimental‐theoretical study, these PTAs exhibit prominent D–A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA‐TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760‐nm LED lamp (1.2 W cm−2). In vitro and in vivo experimental results revealed that DMA‐TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA–RE reaction as a convenient approach to obtain twisted D–A structured PTAs for effective PTT and probably promote the progress of cancer therapies. [ABSTRACT FROM AUTHOR]