scholarly journals A Novel Marine Natural Product Derived Pyrroloiminoquinone with Potent Activity against Skin Cancer Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 443 ◽  
Author(s):  
Jaden Cowan ◽  
Mohammad Shadab ◽  
Dwayaja H. Nadkarni ◽  
Kailash KC ◽  
Sadanandan E. Velu ◽  
...  
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Skin Cancer ◽  
Cancer Cells ◽  
Natural Product ◽  
The United States ◽  
Marine Natural Product ◽  
Migration And Invasion ◽  
Migration Assay ◽  
Lead Compounds

Non-melanoma skin cancer is one of the major ailments in the United States. Effective drugs that can cure skin cancers are limited. Moreover, the available drugs have toxic side effects. Therefore, skin cancer drugs with less toxic side effects are urgently needed. To achieve this goal, we focused our work on identifying potent lead compounds from marine natural products. Five lead compounds identified from a class of pyrroloiminoquinone natural products were evaluated for their ability to selectively kill squamous cell carcinoma (SCC13) skin cancer cells using an MTT assay. The toxicity of these compounds was also evaluated against the normal human keratinocyte HaCaT cell line. The most potent compound identified from these studies, C278 was further evaluated for its ability to inhibit cancer cell migration and invasion using a wound-healing assay and a trans-well migration assay, respectively. To investigate the molecular mechanism of cell death, the expression of apoptotic and autophagy proteins was studied in C278 treated cells compared to untreated cells using western blot. Our results showed that all five compounds effectively killed the SCC13 cells, with compound C278 being the most effective. Compound C278 was more effective in killing the SCC13 cells compared to HaCaT cells with a two-fold selectivity. The migration and the invasion of the SCC13 cells were also inhibited upon treatment with compound C278. The expression of pro-apoptotic and autophagy proteins with concomitant downregulation in the expression of survival proteins were observed in C278 treated cells. In summary, the marine natural product analog compound C278 showed promising anticancer activity against human skin cancer cells and holds potential to be developed as an effective anticancer agent to combat skin cancer.

scholarly journals Marine Pharmacology in 2016–2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 49
Author(s):  
Alejandro M. S. Mayer ◽  
Aimee J. Guerrero ◽  
Abimael D. Rodríguez ◽  
Orazio Taglialatela-Scafati ◽  
Fumiaki Nakamura ◽  
...  
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Natural Product ◽  
Therapeutic Strategies ◽  
Mechanisms Of Action ◽  
Marine Natural Product ◽  
Lead Compounds ◽  
Antiviral Activities ◽  
Marine Compounds ◽  
Anti Inflammatory

The review of the 2016–2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology research during 2016–2017 assessed 313 marine compounds with novel pharmacology reported by a growing number of investigators from 54 countries. The peer-reviewed literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 123 marine natural products, 111 marine compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 79 marine compounds displayed miscellaneous mechanisms of action which upon further investigation may contribute to several pharmacological classes. Therefore, in 2016–2017, the preclinical marine natural product pharmacology pipeline generated both novel pharmacology as well as potentially new lead compounds for the growing clinical marine pharmaceutical pipeline, and thus sustained with its contributions the global research for novel and effective therapeutic strategies for multiple disease categories.

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Mechanism Of Action ◽  
Marine Natural Products ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Follow Up Studies ◽  
Initial Resistance ◽  
Synthesis And Biological Evaluation

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

Abstract A39: The marine natural product manzamine A targets vacuolar ATPases and autophagy in pancreatic cancer cells.

2012 ◽  
Author(s):  
Georgios Kallifatidis ◽  
Dominic Hoepfner ◽  
Sven Schuierer ◽  
Nicole Hartmann ◽  
Esther Guzmán ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Natural Product ◽  
Marine Natural Product ◽  
Manzamine A ◽  
Pancreatic Cancer Cells ◽  
Vacuolar Atpases

scholarly journals Some Biogenetic Considerations Regarding the Marine Natural Product (−)-Mucosin

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4147 ◽  
Author(s):  
Jens M. J. Nolsøe ◽  
Marius Aursnes ◽  
Yngve H. Stenstrøm ◽  
Trond V. Hansen
Keyword(s):  
Fatty Acids ◽  
Natural Products ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Natural Product ◽  
Polyunsaturated Fatty Acid ◽  
Marine Natural Product ◽  
Structural Pattern ◽  
Different Origin

Recently, the identity of the marine hydrindane natural product (−)-mucosin was revised to the trans-fused structure 6, thereby providing a biogenetic puzzle that remains to be solved. We are now disseminating some of our insights with regard to the possible machinery delivering the established architecture. Aspects with regard to various modes of cyclization in terms of concerted versus stepwise processes are held up against the enzymatic apparatus known to be working on arachidonic acid (8). To provide a contrast to the tentative polyunsaturated fatty acid biogenesis, the structural pattern featured in (−)-mucosin (6) is compared to some marine hydrinane natural products of professed polyketide descent. Our appraisal points to a different origin and strengthens the hypothesis of a polyunsaturated fatty acids (PUFA) as the progenitor of (−)-mucosin (6).

Natural products as modulators of the cyclic-AMP pathway: evaluation and synthesis of lead compounds

2018 ◽  
Vol 16 (35) ◽  
pp. 6372-6390 ◽  
Author(s):  
Saumitra Sengupta ◽  
Goverdhan Mehta
Keyword(s):  
Natural Products ◽  
Cyclic Amp ◽  
Total Synthesis ◽  
Natural Product ◽  
Lead Compounds ◽  
Camp Pathway

Natural product modulators of the cAMP pathway have been evaluated and their total synthesis campaign is described in detail.

scholarly journals Targeting Autophagy Peptidase ATG4B With A Novel Natural Product Inhibitor Azalomycin F4a For Advanced Gastric Cancer

2021 ◽  
Author(s):  
Lin Zhong ◽  
Bin Yang ◽  
Zhenhua zhang ◽  
Xiaojuan Wang ◽  
Yinfeng Guo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Natural Product ◽  
Advanced Gastric Cancer ◽  
Therapeutic Target ◽  
Marine Natural Product ◽  
Migration And Invasion ◽  
Enzyme Activity Assay ◽  
Cell Viability Assay

Abstract Background: Advanced gastric cancer (GCa) remains highly lethal due to the lack of effective therapies. Identifying promising therapeutic targets and developing effective treatment against GCa are urgently needed. Here, we investigated whether Autophagy-related gene 4B (ATG4B) could be a potential therapeutic target against GCa and identified marine natural product Azalomycin F4a (Am-F4a) as a potent ATG4B inhibitor and a potential anticancer agent. Methods: The expression of ATG4B in clinical GCa tumor specimens were examined by immunoblotting and interrogation of public databases. The association between ATG4B expression and patient’s survival was assessed. FRET, surface plasmon resonance, transmission electron microscopy analysis, enzyme activity assay and compute docking were used to assess the binding and inhibition of ATG4B by Am-F4a. RNA interference, inhibitors, CCK-8 cell viability assay, colony formation, apoptosis assay, wound-healing, transwell invasion assay, western blotting and Patient-derived organoids were used to assess the role of ATG4B in GCa cells. GCa cell-derived xenograft models, patient-derived xenografts and orthotopic metastasis xenografts were used to evaluate the anti-tumor growth and anti-metastasis effects of Am-F4a alone or in combination with 5-FU in vivo.Results: ATG4B was highly upregulated in GCa tumors. Its high expression was associated with patient’s poor prognosis. knockdown of ATG4B significantly inhibited GCa cell survival and tumor growth. Am-F4a was identified as a novel and potent ATG4B inhibitor. Am-F4a effectively inhibited GCa cell autophagy and growth via targeting ATG4B both in vitro and in vivo. Besides, both pharmacological inhibition and knockdown of ATG4B significantly suppressed GCa cell migration and invasion. Am-F4a potently blocked the metastasis of primary GCa tumors and effectively sensitized tumors to chemotherapy.Conclusion: These findings indicate that ATG4B is a potential novel therapeutic target against GCa and that the natural product Am-F4a is a novel ATG4B inhibitor that can be further developed for treatment of GCa.

scholarly journals TULSI: A MIRACLE HERB USED IN THE TREATMENT OF MANY ILLNESSES: A REVIEW

2021 ◽  
Vol 11 (3) ◽  
pp. 72-85
Author(s):  
PRABHA SHANKAR MAURYA ◽  
◽  
MOHD. JAVED NAIM ◽  
RAJIB K. SINGH ◽  
JAINUL BASHAR ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Side Effects ◽  
Disease Prevention ◽  
Natural Product ◽  
Biological Function ◽  
Ocimum Sanctum ◽  
Active Ingredients ◽  
Health Promoting ◽  
Holy Basil

Tulsi, the famous "unmatched" plant of India, is one of the most popular and beneficial of the numerous therapeutic and health-promoting herbs. Ayurvedic and Unani systems Medicinal natural products are increasingly being investigated in clinical trials for superior pharmacological responses and lack of side effects compared to symptomatic agents. Ocimum sanctum, often referred to as "Holy Basil" or "Tulsi," is known in the traditional Ayurvedic literature for its use in the treatment of many illnesses. The active ingredients obtained from plants, and their biological function in disease prevention have stimulated people's curiosity. This overview includes the nomenclature of plant vesicles, their components, and their use in the treatment of diseases. KEYWORDS: Illness, Ayurveda, Diseases, Treat, Tulsi, Natural product, Plant

scholarly journals Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers

2019 ◽  
Vol 20 (8) ◽  
pp. 2010 ◽  
Author(s):  
Durray Shahwar ◽  
Muhammad Javed Iqbal ◽  
Mehr-un Nisa ◽  
Milica Todorovska ◽  
Rukset Attar ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Cells ◽  
Natural Product ◽  
Apoptotic Cell ◽  
Surface Expression ◽  
Death Receptors ◽  
Cell Surface Expression ◽  
Trail Receptors ◽  
Apoptotic Proteins ◽  
Induced Apoptosis

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers.

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