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Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.

Marine-derived bisindoles exhibit structural diversity and exert anti-cancer influence through multiple mechanisms. Comprehensive research has shown that the development success rate of drugs derived from marine natural products is four times higher than that of other natural derivatives. Currently, there are 20 marine-derived drugs used in clinical practice, with 11 of them demonstrating anti-tumor effects. This article provides a thorough review of recent advancements in anti-tumor exploration involving 167 natural marine bisindole products and their derivatives. Not only has enzastaurin ent

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… Several staurosporine derivatives were isolated from the rice solid fermentation broth of the marine-derived Streptomyces sp. NB-A13. … Indimicin B ( 160 ) ( Figure 10 ), a bisindole alkaloid isolated from the marine streptomyces SCSIO 03032, features a unique 1′, 3′-dimethyl-2′-hydroindole moiety. …

Влияние ПГПР на структуру микробиологической сообщества ризосферы и урожайность солончаковых зерновых культур.

Растворяющиеся в почве бактерии, способствующие росту растений (PGPR), могут защищать растения от почвенных заболеваний и абиотических стрессовых условий. Основная цель данного исследования заключалась в оценке влияния различных PGPR (TF1, TF2, TF3 и TF4) на микробную сообщество ризосферы зерна для корма в солончаково-щелочной поле с использованием высокопроизводительной технологии последовательного секвенирования Illumina MiSeq. Результаты показали, что различные PGPRs значительно увеличили плотность уборки (на 21,31–45,16%), высоту растения (на 9,12–19,98%), диаметр стебля (на 30,07–45,78%)

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… The genera Streptomyces and Arthrobacter are important members of the phylum Actinobacteria. They are not only decomposers of organic matter but also capable of suppressing soil-borne pathogens. … It was also suggested that the disease-suppressive and growth-promoting effects of B. megaterium on cucumber plants might be due to the significant increase in the relative abundances of Nocardioides and Streptomyces [ 34 ]. 4. Materials and Methods 4.1. …

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

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… peucetius, Streptomyces coeruleorubidus | Lysosomal V-ATPase suppression | Antibiotic Antitumor | Approved for range of human cancers | Universal V-ATPase inhibitor [ 101 , 102 ] Fusion and degradation | Cleistanthin-A | | Diphyllin glycoside | Tropical plant Cleistanthus collinus | Lysosomal V-ATPase … Docking and Fusion Stage Inhibitors Polyether ionophores, such as monensin and nigericin, are produced by Streptomyces species and are potent antimicrobial and anticancer agents that belong to a large class of naturally occurring polyketides [ 76 ]. …

Marine Natural Products with Activities against Prostate Cancer: Recent Discoveries.

Prostate cancer is the most common cancer in men, with over 52,000 new cases diagnosed every year. Diagnostics and early treatment are potentially hindered by variations in screening protocols, still largely reliant on serum levels of acid phosphatase and prostate-specific antigen, with tumour diagnosis and grading relying on histopathological examination. Current treatment interventions vary in terms of efficacy, cost and severity of side effects, and relapse can be aggressive and resistant to the current standard of care. For these reasons, the scientific community is looking for new chemoth

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… Hawas et al. [ 47 ] cultured the bacterium Streptomyces sp. Mei37, isolated from the muddy sediment of Jade Bay on the southern German North Sea coast, and performed solid phase and ethyl acetate extractions. … More recently, a secondary metabolite, named Lu01-M, was isolated from the marine actinomycetes Streptomyces sp., collected from marine sediments at 400 m depth in Taiwan. …

Promising Activities of Marine Natural Products against Hematopoietic Malignancies.

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially avai

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… https://dtp.cancer.gov/timeline/flash/success_stories/s2_taxol.htm ; Accessed on 6 May 2021); vinblastine and vincristine, isolated from the Madagascar periwinkle Catharanthus roseus and used for the treatment of a variety of cancers [ 7 ]; and doxorubicin, an anthracycline antibiotic isolated from Streptomyces … Recently, Tangerina et al. [ 147 ] studied the metabolites produced by the marine Streptomyces sp. BRB081 strain cultivated in six different media over different days (by using the one strain many compounds (OSMAC) approach). …

Marine Natural Products as Potent Anticancer Agents (2020-2024): Structural Diversity, SARs and Target Prediction.

In recent years, Marine Natural Products (MNPs) have emerged as a significant source for anticancer drug discovery, as many natural products can offer structural diversity, unique mechanisms of action, and relatively low toxicity. This article provides a systematic review of MNPs with reported anticancer activities from 2020 to 2024. These compounds are classified into seven major categories: terpenoids, alkaloids, sterols, polyketides, peptides and proteins, polysaccharides, and macrolides. For each category, we elaborate on the marine sources, structural identification, in vitro anticancer a

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… In 2020, Chen’s research group isolated and identified 69 natural indolocarbazole alkaloids from the ethyl acetate extracts of four marine-derived Streptomyces strains, including 15 novel compounds ( Figure 13 ) [ 47 ]. … The most potent polyketides derive from marine fungi (Pyrenochaetopsis, Aspergillus, Penicillium) and actinomycetes (Streptomyces). …

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

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… For this purpose, in 1960 the constituted workgroup started to study a Streptomyces strain, Streptomyces peucetius , found near Castel del Monte (Apulia). … The first mTOR inhibitor was rapamycin derived from Streptomyces hygroscopicus . …

Antiangiogenic Potential of Microbial Metabolite Elaiophylin for Targeting Tumor Angiogenesis.

Angiogenesis plays a very important role in tumor progression through the creation of new blood vessels. Therefore, angiogenesis inhibitors could contribute to cancer treatment. Here, we show that a microbial metabolite, elaiophylin, exhibits potent antiangiogenic activity from in vitro and in vivo angiogenesis assays. Elaiophylin dramatically suppressed in vitro angiogenic characteristics such as proliferation, migration, adhesion, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by vascular endothelial growth factor (VEGF) at non-toxic concentrations.

Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, inclu

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… Streptomyces coeruleorubidus or S. peucetius bacteria naturally produce it. … It was an antitumor antibiotic that bound to DNA, also first found in Streptomyces griseous . It was used as a chemotherapeutic agent and worked by stopping replication and transcription. …

Aminopeptidase N: a multifunctional and promising target in medicinal chemistry.

Aminopeptidase N (APN) is a zinc metalloproteinase present in almost all types of organisms and has various functions. Many of them are unrelated to its catalytic activity, which is why APN is sometimes classified as a moonlighting enzyme. APN is involved in carcinogenesis and angiogenesis. It also works as an entrance receptor for some coronaviruses and acts as a mediator during skin inflammation. Additionally, APN removes and helps to recycle regulatory proteins including neuropeptides, which is why its inhibitors hold therapeutic potential for a wide range of diseases, making the design and

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… inhibitor, tested and used for various therapeutic activities. 72–83 Amastatin ( Fig. 6 ) is a tetrapeptide, in particular (2 S ,3 R )-3-amino-2-hydroxy-5-methylhexanoyl- l -Val– l -Val– l -Asp. 84 It also comes from Streptomyces genus, strain code ME 98-M3. 85 In addition to APN, it also inhibits … ME 98-M3. 84–89 Actinonin, a pseudotripeptide ( Fig. 7 ), (2 R )- N ′-hydroxy- N -[(2 S )-1-[(2 S )-2-(hydroxymethyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-pentylbutanediamide ( Fig. 7 ), is a product of Streptomyces roseopallidus . …

Microorganisms Associated with the Marine Sponge Scopalina hapalia: A Reservoir of Bioactive Molecules to Slow Down the Aging Process.

Aging research aims at developing therapies that delay normal aging processes and some related pathologies. Recently, many compounds and extracts from natural products have been shown to slow aging and/or extend lifespan. Marine sponges and their associated microorganisms have been found to produce a wide variety of bioactive secondary metabolites; however, those from the Southwest of the Indian Ocean are much less studied, especially regarding anti-aging activities. In this study, the microbial diversity of the marine sponge Scopalina hapalia was investigated by metagenomic analysis. Twenty-s

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… In 2015, Vicente and co-workers reported the isolation of six new angucyclinone (aromatic polyketide) derivatives from a Streptomyces strain associated with S. ruetzleri [ 102 ]. … Monacyclinones, new angucyclinone metabolites isolated from Streptomyces sp. M7_15 associated with the puerto rican sponge Scopalina ruetzleri. Mar. Drugs. 2015;13:4682–4700. doi: 10.3390/md13084682. 103. Bode H.B., Bethe B., Höfs R., Zeeck A. …

Биоинформатический анализ взаимодействия миелинов и микробов говорит о том, что в патогенезе множественных склерозов присутствуют различные виды молекулярной имитации.

Множественный склероз (MS) — разрушительная аутоиммунная болезнь, приводящая к разрушению милиновой оболочки в центральной нервной системе человека (КНС). Было установлено, что инфекция вирусов и бактерий тесно связана с наступлением мороза или его остротой. Мы предположили, что атака иммунной системы на милиновую оболочку может быть спровоцирована вирусами и бактериальными антигенами, которые напоминают компоненты миелиновой оболочки. Для выявления вирусных и бактериальных антигенов, похожих на миелин олигодендроцит гликпротеин (МОГ) и миелинский основной протеин (МБП), был применен подход, о

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… The elmGT protein of Streptomyces bacteria, which is involved in the biosynthesis of alaromycin and glucose transport, was also identified. … Aspergillus fumigatus | Klebsiella pneumoniae | Schizosaccharomyces pombe | Burkholderia thailandensis | Burkholderia cenocepacia | Bordetella avium | Mycobacterium paratuberculosis | Synechocystis sp | Streptomyces olivaceus | Thermosynechococcus elongatus P | P | P | P | P | P | A | L | L | L G | G …

Thiostrepton Suppresses the Progression of Rhabdomyosarcoma by Inhibiting the PI3K-AKT Signaling Pathway.

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma with 5-year survival below 30% in high-risk/metastatic cases, was investigated through integrated bioinformatics analysis (identifying 269 conserved differentially expressed genes in GEO datasets GSE28511/GSE141690) and experimentally validated thiostrepton (TST), a ribosomal-targeting antibiotic, as a potent therapeutic candidate via Connectivity Map analysis (p p AKT, JAK, CDKs). This was confirmed by PI3K activator 740 Y-P rescue experiments, which partially reversed the effects of TST (p < 0.05). These findings establish

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… Thiostrepton (TST), a structurally unique and biologically diverse compound, was first isolated from Streptomyces azureus in 1954 and initially used as a veterinary antibiotic for bacterial infections [ 12 ]. … Cundliffe E., “Mechanism of Resistance to Thiostrepton in the Producing‐Organism Streptomyces Azureus,” Nature 27, no. 5656 (1978): 792–795: [PubMed], 10.1038/272792a0. 13. …

Awareness of Obesity-Related Cancers: A Complex Issue.

Cancer rates are on the rise across the world, making the illness a public health crisis, particularly in developed countries where cancer has become a leading cause of death [...].

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… Streptomyces, shared microbiome member of soil and gut, as ‘old friends’ against colon cancer FEMS Microbiol. Ecol. 2018 94 fiy120 10.1093/femsec/fiy120 29912397 10. Hooper L. Anderson A.S. Birch J. Forster A.S. Rosenberg G. Bauld L. Vohra J. …

Drug repurposing for breast cancer therapy: Old weapon for new battle.

Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process o

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… Inhibits DNA replication by damaging genetic material of the cell As immuno-modulator in autoimmune diseases Thiotepa Thioplex, Tespa, Thiophosphoamide, TSPA, Tepadina Early and advanced Immunosuppressant Anthracyclins Doxorubicin Adriamycin, Caelyx, Rubex Advanced DNA intercalation Antibiotic from Streptomyces … These are generally extracted from Streptomyces bacterium. Approved for medical use in 1974, doxorubicin (14-hydroxylated version of Daunorubicin) [ 79 ] was originally extracted from Streptomyces peucetius [ 80 ]. …

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats.

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Tra

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… A novel Ni-SOD recently isolated from Streptomyces and marine cyanobacteria catalyzes the dismutation of O 2 − into O 2 and H 2 O 2 through a Ni 2+ /Ni 3+ oxidation cycle [ 23 ]. … Unique isozymes of superoxide dismutase in Streptomyces griseus. Arch Biochem Biophys. 1996;334:341–348. doi: 10.1006/abbi.1996.0463. 24. Lee WZ, Chiang CW, Lin TH, Kuo TS. A discrete five-coordinate Ni(III) complex resembling the active site of the oxidized form of nickel superoxide dismutase. …

Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literat

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… In 2000, belactosin A and C were isolated from Streptomyces sp. by Asai et al. [ 72 ] ( Figure 17 ). These compounds exhibited antitumor activity attributed to the inhibition of proteasome activity. … Belactosin A, a Novel antitumor antibiotic acting on cyclin/CDK mediated cell cycle regulation, produced by Streptomyces sp. J. Antibiot. 2000;53:81–83. doi: 10.7164/antibiotics.53.81. 73. Asai A., Tsujita T., Sharma S.V., Yamashita Y., Akinaga S., Funakoshi M., Kobayashi H., Mizukami T. …

The prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy: A systematic review and meta-analysis.

BackgroundIt is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effect on improving prognosis remains largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy.MethodsA detailed review of English and Chinese literature was conducted up to March 21, 2020. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence inter

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… It is a cytotoxic anthracycline antibiotic extracted from Streptomyces peucetius var. caesius . [ 6 – 7 ] PLD is the first FDA-approved anticancer nano-drug and has demonstrated tremendous benefits. … Limitations in doxorubicin production from Streptomyces peucetius . Microbiol Res 2010;165:427–35. [8] Gabizon AA, Patil Y, La-Beck NM. New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy. Drug Resist Updat 2016;29:90–106. [9] Muggia FM. …

Миксобактериальная реакция на воздействие метильясмоната свидетельствует о вкладе в набор микропрепараторов на заводы.

Химические обмены между растениями и микробами в пределах ризобиомы имеют решающее значение для развития общинной структуры. Такие летучие корневые экюды, как фитохормоновый метилжасмонат (MeJA), способствуют принятию различных мер реагирования в связи со стрессом на растения, и они были причастны к тому, чтобы играть определенную роль в поддержании микробных сообществ. Миксобактерия является компетентным хищником растительных патогенов и, как правило, считается полезной для ризобиомов. Хотя было предложено использовать миксобактерию растений для защиты от патогенов, не известно о каких-либо с

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… Although production of α-bisabolol and characterization of the corresponding synthase ( AB621339.1 ) from Streptomyces citricolor have been reported, no homology to this synthase was observed when comparing the six putative terpene synthases from A. sp. identified by antiSMASH ( Nakano et al., 2011 ; … Genome mining reveals two novel bacterial sesquiterpene cyclases: (−)-germacradien-4-ol and (−)-epi-alpha-bisabolol synthases from Streptomyces citricolor . Chembiochem 12 2271–2275. 10.1002/cbic.201100418 Olanrewaju O. S., Ayangbenro A. S., Glick B. R., Babalola O. O. (2019). …

Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.

Marine-derived compounds represent a rich source of structurally diverse molecules with therapeutic potential for cancer, renal disorders, metabolic-associated fatty liver disease (MAFLD), and atherosclerosis. This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A2-2), ilimaquinone, and Aplidin (plitidepsin). Key mechanisms include autophagy modulation, immune checkpoint inhibition, anti-inflammatory effects, and mitochondrial homeostasis. Novel findings reveal glycosides' dua

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… (clinical) | Disrupts viral replication, modulates immune response | SARS-CoV-2 | Shortened clinical improvement time in patients | [ 36 ] 10 | Renal | S14 | Streptomyces spp. | 5 mg/kg (free); 5 mg/kg (nanoparticles) i.v. | Activates PRDX1/Nrf2, reduces oxidative stress, enhances autophagy | UIRI mouse … The Role of S14 Previously, 43 natural piericidins from two marine-derived Streptomyces strains [ 133 , 134 , 135 ] have emerged as promising candidates for drug development due to their unique bioactivities. …