Chapter 12. From Natural Product to Clinical Trials: NPI-0052 (Salinosporamide A), a Marine Actinomycete-Derived Anticancer Agent

2009 ◽  
pp. 355-373 ◽  
Author(s):  
Kin S. Lam ◽  
G. Kenneth Lloyd ◽  
Saskia T. C. Neuteboom ◽  
Michael A. Palladino ◽  
Kobi M. Sethna ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural Product ◽  
Anticancer Agent ◽  
Salinosporamide A ◽  
Marine Actinomycete

Exploration and engineering of biosynthetic pathways in the marine actinomycete Salinispora tropica

2009 ◽  
Vol 81 (6) ◽  
pp. 1075-1084 ◽  
Author(s):  
Markus Nett ◽  
Bradley S. Moore
Keyword(s):  
Natural Products ◽  
Metabolic Pathways ◽  
Anticancer Agent ◽  
Complex Molecules ◽  
Dna Cleaving ◽  
Metabolic Plasticity ◽  
Salinosporamide A ◽  
Salinispora Tropica ◽  
Marine Actinomycete ◽  
Key Genes

In recent years, members of the marine actinomycete genus Salinispora have proven to be a precious source of structurally diverse secondary metabolites, including the potent anticancer agent salinosporamide A and the enediyne-derived sporolides. The tremendous potential of these marine-dwelling microbes for natural products biosynthesis, however, was not fully realized until sequencing of the Salinispora tropica genome revealed the presence of numerous orphan biosynthetic loci besides a plethora of rare metabolic pathways. This contribution summarizes the biochemical exploration of this prolific organism, highlighting studies in which genome-based information was exploited for the discovery of new enzymatic processes and the engineering of unnatural natural products. Inactivation of key genes within the salinosporamide pathway has expanded its inherent metabolic plasticity and enabled access to various salinosporamide derivatives by mutasynthesis. New insights into the biosynthesis of the sporolides allowed us to increase production titers of these structurally complex molecules, thereby providing the means to search for the DNA cleaving presporolide enediyne.

Natural Products and the Athlete: Facts and Folklore

1993 ◽  
Vol 27 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Richard L. Barron ◽  
Gordon J. Vanscoy
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Natural Product ◽  
Sports Medicine ◽  
Animal Studies ◽  
Data Extraction ◽  
Scientific Evidence ◽  
Pharmacy Practice ◽  
Health Food ◽  
Medline Search

OBJECTIVE: To contrast scientific facts with suggested manufacturers' claims regarding food supplements (natural products) marketed for enhanced athletic prowess. DATA SOURCES: A MEDLINE search was performed to obtain documentation supporting the claims of natural-product manufacturers. In addition, several references pertaining to pharmacognosy, natural products, herbs, pharmacy practice, and sports medicine were reviewed. Claims were obtained from promotional advertisements in bodybuilding magazines, product labels, and fact sheets for sales representatives in nutrition and health-food stores. DATA EXTRACTION: We reviewed all of the clinical trials, published between 1966 and 1992, relative to the manufacturers' claims regarding these products. DATA SYNTHESIS: Pertinent human and/or animal studies supporting each natural product were compared with the manufacturers' claims. CONCLUSIONS: We found that there was no published scientific evidence to support the promotional claims for a large proportion of the products (8/19,42 percent). Only 4 of 19 products (21 percent) were associated with any documented human clinical trials supporting their promotional claims. Six of 19 agents (32 percent) had some scientific documentation to support their promotional claims; however, these products were judged to be marketed in a misleading manner.

scholarly journals (−)-Homosalinosporamide A and Its Mode of Proteasome Inhibition: An X-ray Crystallographic Study

Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 240 ◽  
Author(s):  
Michael Groll ◽  
Henry Nguyen ◽  
Sreekumar Vellalath ◽  
Daniel Romo
Keyword(s):  
Natural Product ◽  
Active Site ◽  
Late Stage ◽  
Enzyme Assay ◽  
Proteasome Inhibition ◽  
Fine Tuning ◽  
Synthetic Approach ◽  
X Ray ◽  
Salinosporamide A ◽  
Crystallographic Study

Upon acylation of the proteasome by the β-lactone inhibitor salinosporamide A (SalA), tetrahydrofuran formation occurs by intramolecular alkylation of the incipient alkoxide onto the choroethyl sidechain and irreversibly blocks the active site. Our previously described synthetic approach to SalA, utilizing a bioinspired, late-stage, aldol-β-lactonization strategy to construct the bicyclic β-lactone core, enabled synthesis of (–)-homosalinosporamide A (homoSalA). This homolog was targeted to determine whether an intramolecular tetrahydropyran is formed in a similar manner to SalA. Herein, we report the X-ray structure of the yeast 20S proteasome:homoSalA-complex which reveals that tetrahydropyran ring formation does not occur despite comparable potency at the chymotrypsin-like active site in a luminogenic enzyme assay. Thus, the natural product derivative homoSalA blocks the proteasome by a covalent reversible mode of action, opening the door for further fine-tuning of proteasome inhibition.

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

A transition metal-free approach to a regioselective total synthesis of the natural product derivative 6-methylellipticine, a potent anticancer agent

2019 ◽  
Vol 60 (51) ◽  
pp. 151309 ◽  
Author(s):  
Song-Bo Lin ◽  
Wan-Wan Wang ◽  
Jin-Peng Meng ◽  
Xi-Wang Li ◽  
Jun Wu ◽  
...  
Keyword(s):  
Transition Metal ◽  
Total Synthesis ◽  
Natural Product ◽  
Anticancer Agent ◽  
Metal Free

scholarly journals Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters

Microbiology ◽  
2016 ◽  
Vol 162 (12) ◽  
pp. 2075-2086 ◽  
Author(s):  
Michelle A. Schorn ◽  
Mohammad M. Alanjary ◽  
Kristen Aguinaldo ◽  
Anton Korobeynikov ◽  
Sheila Podell ◽  
...  
Keyword(s):  
Natural Product ◽  
Gene Clusters ◽  
High Density ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Marine Actinomycete

A Review on Recent Developments in the Anticancer Potential of Oleanolic acid and its analogs (2017-2020)

2021 ◽  
Vol 21 ◽  
Author(s):  
Nidhi Gupta
Keyword(s):  
Clinical Trials ◽  
Natural Product ◽  
Oleanolic Acid ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Pentacyclic Triterpenoid ◽  
Recent Developments ◽  
Anti Inflammatory ◽  
Pharmaceutical Properties

: Oleanolic acid (OA) is a pentacyclic triterpenoid class of natural product known to possess a broad range of biological activities, specifically, anticancer. Considering the anticancer potential of OA, a large number of analogs have been prepared by several researchers through modifications at C-3, C-12 and C-28 –COOH to develop the potent anticancer agents with improved cytotoxicity and pharmaceutical properties. Some of the synthesized derivatives have been assessed in clinical trials also. This review summarizes the most recent synthetic and biological efforts in the development of oleanolic acid and its analogs during the period 2017-2020. Reports published during this period revealed that both OA and its analogs possess a remarkable potential for the development of effective anticancer agents along with several others such as anti-inflammatory, anti-viral, anti-microbial and anti-diabetic agents.

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