noscapine (CB 3304) / J&J - LARVOL DELTA

Genome and transcriptome of Papaver somniferum Chinese landrace CHM indicates that massive genome expansion contributes to high benzylisoquinoline alkaloid biosynthesis. (PubMed, Hortic Res) - "Opium poppy (Papaver somniferum) is a source of morphine, codeine, and semisynthetic derivatives, including oxycodone and naltrexone...Variations between the 2.62 Gb CHM genome and that of the previously sequenced high noscapine 1 (HN1) variety were also explored...Genes carrying structural variations and large-effect variants associated with agronomically different phenotypes between CHM and HN1 that were identified through our transcriptomic comparison of multiple organs and developmental stages can enable the development of new varieties. These genomic and transcriptomic analyses will provide a valuable resource that informs future basic and agricultural studies of the opium poppy."

Journal

Decoding the silent walk of COVID-19: Halting its spread using old bullets. (PubMed, Biomed Pharmacother) - "Among these, remedesivir (RMD), chloroquine (CQ), hydroxychloroquine (HCQ), noscapine (NOS) and heparin have demonstrated fairly promising results in preclinical and clinical studies. In addition, the role of RMD, CQ, HCQ, NOS and heparin in combating infection has been addressed. The importance of vitamin C and D supplements as adjunct therapies in the prevention of SARS-CoV2 virus infection have also been summarized."

Journal • Review • Cardiovascular • Critical care • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Opium Alkaloids in Harvested and Thermally Processed Poppy Seeds. (PubMed, Front Chem) - "The opium alkaloids (morphine, codeine, thebaine, noscapine, and papaverine) have been detected on poppy seeds; they are widely used by the food industry for decoration and flavor but can introduce opium alkaloids into the food chain...In this work, it was found that in harvested poppy seeds, and thermally processed poppy seeds (with and without a food matrix), if used in normal levels would not exceed the recommended acute reference dose. It was also shown that the levels of all alkaloids reduce when thermally processed, in comparison with harvested, untreated seeds."

Journal

Biological Evaluation of Noscapine analogues as Potent and Microtubule-Targeted Anticancer Agents. (PubMed, Sci Rep) - "Consistent to in vitro cytotoxicity data, 9-hydroxy methyl analogue of Nos induced significantly (P < 0.05) higher degree of apoptosis of 84.6% in U87 cells as compared to 78.5% and 64.3% demonstrated by 9-carbaldehyde oxime and Nos, respectively. Thus the higher therapeutic efficacy of 9-hydroxy methyl analogue of Nos may be credited to higher solubility and inhibitory constant (K)."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Research progress of Pictet-Spenglerases (PubMed, Sheng Wu Gong Cheng Xue Bao) - "The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development."

Journal

DFT and docking studies of designed conjugates of noscapines & repurposing drugs: promising inhibitors of main protease of SARS-CoV-2 and falcipan-2. (PubMed, J Biomol Struct Dyn) - "Further, infrared and Raman spectra of the designed hybrid molecules were determined and studied. Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Malaria • Novel Coronavirus Disease • Oncology

Comparative binding analysis of noscapine and piperine with tRNA: A structural perturbation and energetic study. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Molecular docking studies are comparable with experimental results and further confirmed that the hydrophobic interactions involved in the NOS-tRNA binding, whereas hydrogen binding and van der Waals interactions play important role in the PIP-tRNA complex formation. This study can be useful to understand the potential binding and resultant tRNA damage by alkaloids and deigned new target specific anticancer drug."

Journal • Oncology

N-substituted noscapine derivatives as new antiprotozoal agents: Synthesis, antiparasitic activity and molecular docking study. (PubMed, Bioorg Chem) - "Molecular docking was carried out on trypanothione reductase (TbTR, PDB ID: 2WOW) and UDP-galactose 4' epimerase (TbUDPGE PDB: 1GY8) as targets for studying the envisaged mechanism of action. Compounds 6j and 6b displayed excellent docking scores with -8.59 and -8.86 kcal/mol for TbTR and TbUDPGE, respectively."

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Noscapine alleviates cerebral damage in ischemia-reperfusion injury in rats. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The study demonstrates the protective effect of noscapine in yeast and I-R rats by improving cell viability and attenuating neuronal damage, respectively. This protective activity of noscapine could be attributed to potent free radical scavenging and inhibition of inflammation in cerebral ischemia-reperfusion injury."

Journal • Cardiovascular • Immunology • Inflammation • Reperfusion Injury • MPO

A Combinational Approach Towards Treatment of Breast Cancer: an Analysis of Noscapine-Loaded Polymeric Nanoparticles and Doxorubicin. (PubMed, AAPS PharmSciTech) - "Immunohistochemical (IHC) analysis of the tumor tissues confirmed antiangiogenic effect of Nos NPs. The findings highlighted efficacy of Nos NPs alone and in combination with Dox HCl on breast cancer tumors."

Journal • Breast Cancer • Oncology • Solid Tumor

Tubulin- and ROS-dependent antiproliferative mechanism of a potent analogue of noscapine, N-propargyl noscapine. (PubMed, Life Sci) - "NPN can be explored further as a chemotherapeutic agent against TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

9-PAN promotes tubulin- and ROS-mediated cell death in human triple-negative breast cancer cells. (PubMed, J Pharm Pharmacol) - "9-PAN exerts its antiproliferative effect by targeting tubulin and elevating ROS level in the cells."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Rapid screening of trace volatile and nonvolatile illegal drugs by miniature ion trap mass spectrometry: synchronized flash-thermal-desorption purging and ion injection. (PubMed, Anal Chem) - "The flash-thermal desorption could reach 290 °C in 2.5 s, which could achieve efficient vaporization of nonvolatile noscapine with boiling point at 565 °C. The miniature SFTDPI-ITMS presents good performance: 1) more than 60 times improvement in sensitivity was achieved compared with the previously reported thermal desorption acetone-assisted photoionization ion trap mass spectrometer (TD-AAPI-ITMS) for nonvolatile drugs, and the minimum detectable quantity reach to 50 picograms for fentanyl; 2) ten kinds of mixing drugs with boiling point difference of 300 °C can be simultaneously identified within 3 seconds under a single analysis. The SFTDPI-ITMS had been deployed at the roadside checkpoint of Sino-Burmese border, fentanyl in the captured encapsulated powder and the suspected opiate had been successfully identified."

Journal

A Novel Class of N-Sulfonyl and N-Sulfamoyl Noscapine Derivatives that Promote Mitotic Arrest in Cancer Cells. (PubMed, ChemMedChem) - "((R)-5-((S)-4,5-Dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-((1-methyl-1H-imidazol-4-yl)sulfonyl)-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinoline) (14 q) displayed sub-micromolar activities of 560, 980, 271 and 443 nM against MCF-7, PANC-1, MDA-MB-435 and SK-MEL-5 cells, respectively. This antiproliferative effect was also maintained against drug-resistant NCI/Adr cells despite high expression of the multidrug efflux pump, P-glycoprotein."

Journal • Oncology

Noscapine Modulates Neuronal Response to Oxygen-glucose Deprivation/Reperfusion Injury Via Activation of Sigma-1 Receptor in Primary Cortical Cultures. (PubMed, Iran J Pharm Res) - "We concluded that noscapine in the presence of BD1047 could protect primary cortical neurons after oxygen-glucose deprivation-induced cell injury but this effect was not complete. Our results indicate that neuroprotective effects of noscapine could be mediated partially through activation of sigma-1 receptor and by decreasing NO production and [Ca]i levels."

Journal • Preclinical • Reperfusion Injury

Sustained release dosage form of noscapine HCl using hot melt extrusion (HME) technique: formulation and pharmacokinetics. (PubMed, Drug Deliv Transl Res) - "Overall, HME can be used to enhance the bioavailability and achieve the pH-independent solubility of weakly basic drugs like Nos HCl. Graphical abstract."

Journal • PK/PD data

Antitussive noscapine and antiviral drug conjugates as arsenal against COVID-19: a comprehensive chemoinformatics analysis. (PubMed, J Biomol Struct Dyn) - "We employed the antitussive noscapine in conjugation with antiviral drugs (Chloroquine, Umifenovir, Hydroxychloroquine, Favlplravir and Galidesivir). Also, we reveal the drugs with stable binding to major domains of Mpro can significantly improve the work profile of reaction coordinates, drug accession and inhibitory regulation of Mpro. The designed combinatorial therapy paves way for further prioritized in vitro and in vivo investigations for drug with robust binding against Mpro of SARS-CoV-2."

Journal • Infectious Disease • Novel Coronavirus Disease

Molecular binding mechanism and pharmacology comparative analysis of noscapine for repurposing against SARS-CoV-2 protease. (PubMed, J Proteome Res) - "The drug repurposing study revealed the high potential of noscapine and proximal binding to the Mpro enzyme in a comparative binding pattern analysed with chloroquine, ribavirin, and favipiravir. Principal component analysis depicted the enhanced movement of protein atoms with a high number of static hydrogen bonds. Obtained binding results of noscapine were also well correlated with pharmacokinetic parameters of antiviral drugs."

Journal • Infectious Disease • Novel Coronavirus Disease

Discovery of noscapine derivatives as potential β-tubulin inhibitors. (PubMed, Bioorg Med Chem Lett) - "Integrating computational predictions and experimental evaluation, two promising compounds (8h and 9c) were identified, whose relevant cytotoxicity was supposed to be correlated with that of tubulin binding affinity. These findings shed more lights onto structural modifications of noscapine toward the identification of more potent cytotoxic agents targeting tubulin."

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Oxidative Stress-Induced Axon Fragmentation Is a Consequence of Reduced Axonal Transport in Hereditary Spastic Paraplegia SPAST Patient Neurons. (PubMed, Front Neurosci) - "Patient axons fragmented significantly more than controls following hydrogen peroxide exposure, suggesting for the first time that the SPAST patient axons are more sensitive than controls to the deleterious effects of oxidative stress. Treatment of patient neurons with tubulin-binding drugs epothilone D and noscapine rescued axon peroxisome transport and protected them against axon fragmentation induced by oxidative stress, showing that SPAST patient axons are vulnerable to oxidative stress-induced degeneration as a consequence of reduced axonal transport."

Clinical • Journal

Over 100 Million Years of Enzyme Evolution Underpinning the Production of Morphine in the Papaveraceae Family of Flowering Plants. (PubMed, Plant Commun) - "K estimation of paralogous pairs indicates that morphine biosynthesis evolved more recently than 18 MYA in the Papaver genus. In the preceding 100 million years gene duplication, neofunctionalization and recruitment of additional enzyme classes, combined with gene clustering, gene fusion, and gene amplification, resulted in emergence of medicinally valuable BIAs including morphine and noscapine."

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Structural basis of noscapine activation for tubulin binding. (PubMed, J Med Chem) - "We suggest that the 7A-methoxy group of noscapine prevents binding to tubulin due to a steric clash of the compound with the T5-loop of α-tubulin. We further propose that the anticancer activity of noscapine arises from a bioactive metabolite that binds to the colchicine site of tubulin to induce mitotic arrest through a microtubule cytoskeleton-based mechanism."

Journal • Oncology

Rational design of 9-vinyl-phenyl noscapine as potent tubulin binding anticancer agent and evaluation of the effects of its combination on Docetaxel. (PubMed, J Biomol Struct Dyn) - "Both agents bind effectively to tubulin in single and in combination to interfere with cell cycle progression in G2/M transition. This study provides novel concept of combination treatment of DOX and VPN to amend efficiency in breast cancer treatment.Communicated by Ramaswamy H. Sarma."

Journal • Breast Cancer • Oncology • Solid Tumor

Noscapine protects the H9c2 cardiomyocytes of rats against oxygen-glucose deprivation/reperfusion injury. (PubMed, Mol Biol Rep) - "The addition of noscapine in the presence of BD1047 did not increase the cell viability relative to noscapine alone. Noscapine exerted cardioprotective effects exposed to OGD/R-induced injury in H9c2 cells, at least partly via attenuation of NO production and Bax/Bcl-2 ratio, which indicates that the sigma-one receptor activation is involved in the protection by noscapine of H9c2 cells injured by OGD/R."

IO Biomarker • Journal • Preclinical • Oncology • Reperfusion Injury • BCL2

Noscapine Induces Apoptosis in Human Colon Cancer Cells by Regulating Mitochondrial Damage and Warburg Effect via PTEN/PI3K/mTOR Signaling Pathway. (PubMed, Onco Targets Ther) - "However, PTEN interference counteracted the effect of noscapine on mitochondrial damage and the Warburg effect in HT29/5-FU and LoVo/5-FU cells by decreasing the activation of PI3K/mTOR signaling. These results indicated that noscapine induced the apoptosis of HT29/5-FU and LoVo/5-FU human colon cancer cells by regulating mitochondria damage and the Warburg effect via PTEN, and the process is closely related to the PI3K/mTOR signaling pathway."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PTEN