Noscapine Research Articles

Synthesis and in vitro study of surface-modified and anti-EGFR DNA aptamer -conjugated chitosan nanoparticles as a potential targeted drug delivery system

Nowadays, finding effective approaches for cancer therapy is one of the significant issues related to human health all over the world. Hence, in this research, we designed and synthesized a novel targeted DDS based on surface-modified chitosan (CS) for the effective delivery of noscapine (NO). As the surface of CS nanoparticles was firstly modified with carboxyl groups and followed by covalent conjugation of DNA-aptamer (Ap) as targeting and receptor blocker agent. Secondly, NO, as a chemotherapeutic agent, was loaded into prepared nano-complex and synthetics were effectively characterized via various analytical devices, including FT-IR, 1H NMR, DLS, Zeta potential analyzer, TGA, TEM, and SEM to verify quality and quantity of synthetics. Drug loading was obtained about 25 % and sustained drug release was observed for nano-complex at different pHs. Then, the cell viability assay was performed on MCF-7 (as breast cancer cell) and HFF-1 (as normal cell) cell lines to investigate cancer cell inhibition potency of nano-complex. Cell viability of cancer cells was 19.84 ± 1.87 % (for C-CS-Ap-NO) and 75.43 ± 2.64 % (for C-CS-Ap) after 72 h of treatment with 400 nM concentration. These results have been confirming the excellent potency of synthesized novel nano-complex as practical DDS in cancer therapy.

The Binding Mechanism Between Cyclodextrins and Anticancer Drug Noscapine: A Spectroscopic and Molecular Docking Study.

In this paper the binding of noscapine (NOS) as an anticancer drug with poor bioavailability and low solubility with beta and methyl-beta cyclodextrins (β-CD and M-β-CD) as the biocompatible drug carriers were discussed using ultraviolet-visible, fluorescence and nuclear magnetic resonance spectroscopy, as well as molecular docking. The absorption of NOS changed when it was bound to both cyclodextrins, resulting in a hyperchromic shift. It formed a 1:1 stoichiometry inclusion complex with both cyclodextrins according to the Benesi-Hildebrand equation. The binding affinity was larger in NOS-M-β-CD (5.9 (± 0.66) × 103 M- 1) than NOS-β-CD (3.7 (± 0.22) × 103 M- 1) complex. The fluorescence emission band of NOS at 408nm was quenched when NOS was complexed with β-CD, and enhanced in the presence of M-β-CD, while the shoulder at 350nm was enhanced selectively when NOS was complexed with M-β-CD. The fluorescence quenching of NOS with β-CD showed a negative deviation from the Stern-Volmer. The thermodynamic parameters have been estimated with the help of the Van't Hoff equation in different temperatures, and a dynamic mechanism was proposed for quenching. Also, both ΔH and ΔS have positive values thus the main interactions result in hydrophobic forces. Moreover, the negative value of ΔG indicates that the bonding process is spontaneous. 1H NMR chemical shift changes were observable for NOS and both CDs protons due to the chemical environment changes of some nuclei upon complexation. The molecular docking results revealed that the 1:1 inclusion complex possesses a good molecular shape complementarity score for their most probable structures, and indicated that the M-β-CD inclusion system gave the higher complexation efficiency. The binding energy values for β-CD and M-β-CD were determined to be -6.7 and - 9.5kcal/mol, respectively. These findings suggest the same as the result of experimental tests that the NOS-M-β-CD complex is more stable than the NOS-β-CD complex.

Exploring the promising potential of noscapine for cancer and neurodegenerative disease therapy through inhibition of integrin-linked kinase-1

Integrin-linked kinase (ILK), a β1-integrin cytoplasmic domain interacting protein, supports multi-protein complex formation. ILK-1 is involved in neurodegenerative diseases by promoting neuro-inflammation. On the other hand, its overexpression induces epithelial–mesenchymal transition (EMT), which is a major hallmark of cancer and activates various factors associated with a tumorigenic phenotype. Thus, ILK-1 is considered as an attractive therapeutic target. We investigated the binding affinity and ILK-1 inhibitory potential of noscapine (NP) using spectroscopic and docking approaches followed by enzyme inhibition activity. A strong binding affinity of NP was measured for the ILK-1 with estimated Ksv (M−1) values of 1.9 × 105, 3.6 × 105, and 4.0 × 105 and ∆G0 values (kcal/mol) −6.19554, −7.8557 and −8.51976 at 298 K, 303 K, and 305 K, respectively. NP binds to ILK-1 with a docking score of −6.6 kcal/mol and forms strong interactions with active-site pocket residues (Lys220, Arg323, and Asp339). The binding constant for the interaction of NP to ILK-1 was 1.04 × 105 M−1, suggesting strong affinity and excellent ILK-1 inhibitory potential (IC50 of ∼5.23μM). Conformational dynamics of ILK-1 were also studied in the presence of NP. We propose that NP presumably inhibits ILK-1-mediated phosphorylation of various downstream signalling pathways that are involved in cancer cell survival and neuroinflammation.

Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions

Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. In this regard, solid lipid nanoparticles (SLN) encapsulated NOS (SLN-NOS) were fabricated using the well-known response surface method based on the central composite design and modified high-shear homogenization and ultrasound method. As a result, Precirol® was selected as the best lipid base for the SLN formulation based on Hildebrand-Hansen solubility parameters, in which SLN-NOS 1 % had the best zeta potential (−35.74 ± 2.59 mV), average particle size (245.66 ± 17 nm), polydispersity index (PDI, 0.226 ± 0.09), high entrapment efficiency (89.77 %), and ICH-based stability results. After 72 h, the SLN-NOS 1 % released 83.23 % and 58.49 % of the NOS at pH 5.8 and 7.4, respectively. Moreover, Franz diffusion cell’s results indicated that the skin levels of NOS for SLN and cream formulations were 46.88 % and 13.5 % of the total amount, respectively. Our pharmacological assessments revealed that treatment with SLN-NOS 1 % significantly attenuated clinical parameters, namely ear thickness, length, and psoriasis area and severity index, compared to the IMQ group. Interestingly, SLN-NOS 1 % reduced the levels of interleukin (IL)-17, tumor necrosis factor-α, and transforming growth factor-β, while elevating IL-10, compared to the IMQ group. Histology studies also showed that topical application of SLN-NOS 1 % significantly decreased parakeratosis, hyperkeratosis, acanthosis, and inflammation compared to the IMQ group. Taken together, SLN-NOS 1 % showed a high potential to attenuate skin inflammation.

Covalent or ionic bonding of Eosin Y to silica: New visible-light photocatalysts for redox wastewater remediation

Eosin Y (EY) is an organic dye widely used as a photoredox catalyst in organic synthesis, but there are only few studies on its use in heterogeneous photocatalysis for the degradation of aqueous Contaminants of Emerging Concern (CECs). In this context, several synthetic strategies were used to prepare heterogeneous silica-based photocatalysts where EY is anchored to glass wool (GW) covalently or using ionic bonds for obtaining GW-C-EY and GW-I-EY, respectively. The percentage of EY linked to GW-C-EY (up to 0.0034% w/w) was always lower than the obtained in GW-I-EY (0.165% w/w). Photodegradation of CECs such as noscapine (NOS), sulfamethoxazole (SMX) and ofloxacin (OFX) was studied using the new heterogeneous photocatalysts in water under visible light irradiation and results showed that only NOS is photodegraded. It was also observed that EY photoreactivity in GW-C-EY and GW-I-EY is quite similar. Interestingly, when the photocatalysts were studied using mixtures of the three CECs, a synergistic effect that favors the photodegradation of SMX and OFX was observed. Specifically, GW-I-EY achieves 100% photodegradation for NOS and ca. 50% removal of SMX and OFX. Based on photophysical and photochemical experiments, redox processes initiated by an electron transfer from NOS to the EY triplet excited state and the subsequent reaction of the generated EY•− with SMX or OFX justify the observed synergistic photodegradation. This finding opens up the possibility of working with complex aqueous matrices and also of smart selecting the combination of different types of contaminated waters to favor the efficiency of the photocatalytic decontamination processes.

Network pharmacology and in vitro experiments reveal that Noscapine induces ROS-mediated apoptosis and cell cycle arrest via PI3K/Akt/FoxO3a signaling pathway in human bladder cancer cells.

Noscapine (NA) has been demonstrated to have antitussive and antitumoral activities. Nonetheless, the potential mechanism of action on Bladder Cancer (BLCA) is yet to be completely grasped. The targets of NA action and bladder cancer disease targets were found by the database. Construct the PPI network. Subsequently, conduct pathway enrichment of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) on core targets. A "drug-disease-target-pathway" network map was made. Cytotoxicity was examined via CCK-8 and colony formation assays. Both a scratch test and a transwell assay confirmed that NA was capable of suppressing the invasiveness and migratory potential of bladder cancer cells. Hoechst 33342 staining was used to visualize NA-induced apoptosis in bladder cancer cells. Flow cytometry was employed to investigate the induction of apoptosis, the distribution of the cell cycle, the production of Reactive Oxygen Species (ROS), and the Mitochondrial Membrane Potential (MMP). The Western blot was applied to show the expression of proteins that are implicated in the pathway, cell cycle, apoptotic process, and proliferation. 198 Noscapine-BLCA-related targets were obtained. GO functional enrichment analysis yielded 428 entries (P < 0.05 and FDR < 0.05). KEGG pathway enrichment analysis identified 138 representative signaling pathways (P < 0.01 and FDR < 0.01). NA concentration-dependently suppressed cell growth and colony formation, along with the invasiveness and migratory potential of bladder cancer cells, by promoting apoptosis, a cell cycle arrest in the G2/M phase, generation of ROS, and depolarization of MMPs. In addition, Western blotting illustrated that NA down-regulated the protein levels associated with pathway, anti-apoptotic proteins, proliferation-related proteins, and cell cycle promoters but up-regulated pro-apoptotic proteins, cell cycle modulators, and Endoplasmic Reticulum (ER) stress expression. Pretreatment with Acetylcysteine N-acetyl-L-cysteine (NAC) and YS-49 counteracted the influence of NA on ROS induction and apoptosis. Noscapine induces ROS-mediated apoptosis and cell cycle arrest via PI3K/Akt/FoxO3a signaling pathway in human BLCA cells.

Topical Formulation of Noscapine, a Benzylisoquinoline Alkaloid, Ameliorates Imiquimod-Induced Psoriasis-Like Skin Lesions.

Psoriasis is considered an autoimmune inflammatory disease. The disease is spread and diagnosed by the infiltration of inflammatory mediators and cells into the epidermis. Recent theoretical developments have focused on the effectiveness of noscapine (NOS) as a potential alkaloid for being used as a valuable treatment for different diseases. In the present study, psoriasis-like dermatitis was induced on the right ear pinna surface of male Balb/c mice by topical application of imiquimod (IMQ) for ten consecutive days, which was treated with noscapine (0.3, 1, 3, and 10% w/v) or clobetasol (0.05% w/v) as a positive control. The levels of ear length, thickness, severity of skin inflammation, psoriatic itch, psoriasis area severity index (PASI) score, and body weight were measured daily. On the 10th day of study, each ear was investigated for inflammation, fibrosis, proliferation, and apoptosis using histopathological (H&E and Masson's trichrome staining) and immunohistochemistry (Ki67 and p53 staining) assays. Furthermore, the levels of inflammatory biomarkers were characterized by an enzyme-linked immunosorbent assay (ELISA). The results confirmed IMQ-induced psoriasis for five consecutive days. In contrast, noscapine significantly reduced the ear length, thickness, severity of skin inflammation, psoriatic itch and body weight, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interferon-gamma (IFN-γ), interleukin 6 (IL-6), IL-17, and IL-23p19 in a concentration-dependent manner (P < 0.001–0.05 for all cases). Overall, topical noscapine significantly ameliorated both the macroscopical and microscopical features of psoriasis. However, further clinical investigations are required to translate the effects to clinics.

Biomimetic photooxidation of noscapine sensitized by a riboflavin derivative in water: The combined role of natural dyes and solar light in environmental remediation.

Noscapine (NSC) is a benzyl-isoquinoline alkaloid discovered in 1930 as an antitussive agent. Recently, NSC has also been reported to exhibit antitumor activity and, according to computational studies, it is able to attack the protease enzyme of Coronavirus (COVID-19) and thus could be used as antiviral for COVID-19 pandemic. Therefore, an increasing use of this drug could be envisaged in the coming years. NSC is readily metabolized with a half-life of 4.5h giving rise to cotarnine, hydrocotarnine, and meconine, arising from the oxidative breaking of the CC bond between isoquinoline and phthalide moieties. Because of its potentially increasing use, high concentrations of NSC but also its metabolites will be delivered in the environment and potentially affect natural ecosystems. Thus, the aim of this work is to investigate the degradation of NSC in the presence of naturally occurring photocatalysts. As a matter of fact, the present contribution has demonstrated that NSC can be efficiently degraded in the presence of a derivative of the natural organic dye Riboflavin (RFTA) upon exposure to visible light. Indeed, a detailed study of the mechanism involved in the photodegradation revealed the similarities between the biomimetic and the photocatalyzed processes. In fact, the main photoproducts of NSC were identified as cotarnine and opianic acid based on a careful UPLC-MS2 analysis compared to the independently synthesized standards. The former is coincident with one of the main metabolites obtained in humans, whereas the latter is related to meconine, a second major metabolite of NSC. Photophysical experiments demonstrated that the observed oxidative cleavage is mediated mainly by singlet oxygen in a medium in which the lifetime of 1O2 is long enough, or by electron transfer to the triplet excited state of RFTA if the photodegradation occurs in aqueous media, where the 1O2 lifetime is very short.

Simultaneous determination of five opium alkaloids in underground waters using molecularly imprinted polymer-modified magnetic nanoparticle based dispersive micro-solid phase extraction followed by high performance liquid chromatography

ABSTRACT In this work, we present a fast, simple and selective method for the extraction/preconcentration and determination of five opium alkaloids. This method is based on the combination of dispersive solid phase extraction with magnetic molecularly imprinted polymers (MMIP) and determination via high performance liquid chromatography. The surface modified Fe3O4 nanoparticles were synthesised in-situ, from a co-precipitation method by addition of a mixture of the methacrylic acid and ammonia to a mixture of Fe2+/Fe3+ under nitrogen atmosphere. MMIP was prepared from surface modified nanoparticles in the presence of ethylene glycol dimethyl acrylate as cross-linker and azobisisobutyronitrile as initiator and template molecule under reflux in acetonitrile. MMIPs for five natural occurring opium alkaloids, including morphine (MO), codeine (CO), thebaine (TE), noscapine (NO) and papaverine (PA) were prepared in the same manner. Structural characterisation and elucidation of both synthesised nanoprticles were performed by Fourier transform-infrared spectroscopy, scanning electron microscopy. X-ray diffraction and vibrating sample magnetometry. A precise chromatographic method was developed and coupled with extraction with MMIP nanoparticles for simultaneous preconcentration and determination of above-mentioned alkaloids in underground water samples. The limit of detection obtained 0.007, 0.007, 0.004, 0.003, 0.003 mg L−1 for MO, CO, TE, NO and PA, respectively and recoveries were about 97–102%. Linear dynamic range and relative standard deviation were 0.03–100 mg L−1 and less than 1.5% for each analyte.

Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium.

Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain (COL1A2) mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-luteal phases at 24 or 48 h of treatment. The COL1A2 mRNA was evaluated by qPCR and COL1 protein relative abundance by Western blot. In equine endometrial explants, ELA increased COL 1 expression, while NOSC inhibited it at both estrous cycle phases and treatment times. These findings contribute to the future development of new endometrosis treatment approaches. Noscapine could be a drug capable of preventing collagen synthesis in mare’s endometrium and facilitate the therapeutic approach.

Electrochemical Measurement of Noscapine and Lorazepam Using a Carbon Paste Electrode Modified with Multi-walled Carbon Nanotubes and Natural Deep Eutectic Solvent.

In the present study, simultaneous voltammetric determination of noscapine (NOS) and lorazepam (LOR) was studied for the first time. A carbon paste electrode modified with multi-walled carbon nanotubes (MWCNTs) and natural deep eutectic solvent (NANADES) (MWCNTs/NADES/CPE) was used for this purpose. Electrochemical impedance spectroscopy (EIS) was applied for the investigation of the electron transfer rate of [Fe(CN)6]3-/4- as a redox couple probe on the surface of the MWCNTs/NADES/CPE. The modified electrode preserved and combined the properties of the individual modifiers synergistically. A significant enhancement in the peak current responses of NOS and LOR was observed on the modified electrode surface compared to the bare electrode. Under the optimal conditions, the peak current of differential pulse voltammograms was linearly dependent on analyte concentration in the range of 3-1700 µM for NOS and 1-2220 µM for LOR. The limit of detection (LOD) for NOS and LOR was 1.90 µM and 0.69 µM, respectively. Finally, this strategy was also employed for the determination of NOS and LOR in pharmaceutical samples.

Comparative binding analysis of noscapine and piperine with tRNA: A structural perturbation and energetic study.

In this study, we have exploring the binding mechanisms of the two anticancer alkaloid noscapine (NOS) and piperine (PIP) with tRNA using different spectroscopy and computational method. Absorbance and emission spectra revealed that both the drugs show strong binding with tRNA, where NOS intercalate between the base pairs of tRNA and PIP binds in the groove of tRNA. Competitive binding study and steady state anisotropy further confirms the intercalative mode of binding between NOS and tRNA and groove binding in PIP-tRNA complex. The observed thermodynamic parameters suggested that NOS-tRNA complex formation is endothermic and entropy driven, however it was exothermic, and enthalpy driven in case of PIP-tRNA complex. CD and time resolved fluorescence studies show the structural perturbations and conformational change in tRNA structure with NOS as well as PIP. 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.

Graphitic carbon nitride-graphene nanoplates; Application in the sensitive electrochemical detection of noscapine

The graphitic carbon nitride-graphene nanoplatelets (g-C3N4/GNP) composite was synthesized. Field Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive X-ray spectroscopy (EDS), Fourier Transform Infrared (FT-IR) spectroscopy, and X-Ray powder Diffraction (XRD) techniques were the techniques employed for the identifying the prepared nanocomposite. The synthesized nanocomposite was used to fabricate a surface modified glassy carbon electrode (g-C3N4/GNP-GCE). This modified electrode was employed for the selective and sensitive detection of noscapine (NOS) by the voltammetric methods LSV, CV and DPV. The results approved that application of the developed working electrode in DPV technique provides a sensitive NOS detection method (LOD 10 nM) in the phosphate buffer (pH 6.0) solution. Under the optimum conditions, the variation of the peak current as a function of the concentration of NOS was linear in the range of 0.05–27.0 μM. The developed working electrode presented acceptable selectivity, stability, repeatability, and reproducibility. The potential of g-C3N4/GNP-GCE was demonstrated by its application for the monitoring of NOS in real samples.

Probing the Intercalation of Noscapine from Sodium Dodecyl Sulfate Micelles to Calf Thymus Deoxyribose Nucleic Acid: A Mechanistic Approach.

Noscapine (NOS) is efficient in inhibiting cellular proliferation and induces apoptosis in nonsmall cell, lung, breast, lymphatic, and prostate cancers. The micelle-assisted drug delivery is a well-known phenomenon; however, the proper mechanism is still unclear. Therefore, in the present study, we have shown a mechanistic approach for the delivery of NOS from sodium dodecyl sulfate (SDS) micelles to calf thymus deoxyribose nucleic acid (ctDNA) base-pairs using various spectroscopic techniques. The absorption and emission spectroscopy results revealed that NOS interacts with the SDS micelle and resides in its hydrophobic core. Further, the intercalation of NOS from SDS micelles to ctDNA was also shown by these techniques. The anisotropy and quenching results further confirmed the relocation of NOS from SDS micelles to ctDNA. The CD analysis suggested that SDS micelles do not perturb the structure of ctDNA, which supported that SDS micelles can be used as a safe delivery vehicle for NOS. This work may be helpful for the invention of advanced micelle-based vehicles for the delivery of an anticancer drug to their specific target site.

SIMULTANEOUS DETERMINATION OF DIPHENHYDRAMINE, EPHEDRINE, NOSCAPINE, AND GLYCEROL GLYCOLATE USING STABILITY-INDICATING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY: APPLICATION TO NOSCOF TABLETS

Objective: Noscof tablet is a fixed dosage combination formulation having diphenhydramine (DH), ephedrine (ED), noscapine (NP), and glycerol glycolate (GG). A sensitive, selective, accurate, precise, and stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method with photodiode array detection has been developed and validated for simultaneous analysis of DH, ED, NP, and GG in bulk drug and Noscof tablets.&#x0D; Methods: Reversed-phase chromatographic separation and analysis of DH, ED, NP, and GG were done on an Altima C18 column with 0.01 M KH2PO4 buffer (pH 3.5) and acetonitrile (50:50%, v/v) as mobile phase at 0.8 ml/min flow rate in isocratic mode. Detection was performed at 260 nm. The method was validated in harmony with International Conference on Harmonization (ICH) guidelines. The tablet sample solution was subjected to diverse stress conditions using ICH strategy such as hydrolytic degradation (neutral - with distilled water, alkaline - with 2 N NaOH, and acidic - with 2 N HCl), oxidation (with 10% H2O2), photodegradation (exposing to UV light), and dry heat degradation (exposing to 105°C).&#x0D; Results: Using the above stated chromatographic conditions, sharp peaks were obtained for ED, NP, DH, and GG with retention time of 3.272 min, 4.098 min, 5.467 min, and 6.783 min, respectively. Good regression coefficient values were obtained in the range of 2–12 μg/ml for ED, 3.75–22.5 μg/ml for NP, 3.125–18.75 μg/ml for DH, and 25–150 μg/ml for GG. The quantification limits were 0.181 μg/ml, 0.187 μg/ml, 0.246 μg/ml, and 1.114 μg/ml for ED, NP, DH, and GG, respectively. The values of validation parameters are within the acceptance limits given by ICH. The ED, NP, DH, and GG showed more percent of degradation in acid condition and less percent of degradation in the neutral condition. The peaks of degradants did not interfere with the peaks of analytes. ED, NP, DH, and GG were assessed with a good percentage of the assay (near to 100%) and low percent relative standard deviation (&lt;2%) in Noscof tablets using the proposed method.&#x0D; Conclusion: The stability indicating RP-HPLC method developed was suitable for quantifying ED, NP, DH, and GG simultaneously in bulk as well as in tablet formulation.

In Vitro Cytotoxicity and Interaction of Noscapine with Human Serum Albumin: Effect on Structure and Esterase Activity of HSA.

Noscapine is effective to inhibit cellular proliferation and induced apoptosis in nonsmall cell, lung, breast, lymphoma, and prostate cancer. It also shows good efficiency to skin cancer cells. In the current work, we studied the mechanism of interaction between the anticancer drug noscapine (NOS) and carrier protein human serum albumin (HSA) by using a variety of spectroscopic techniques (fluorescence spectroscopy, time-resolved fluorescence, UV-visible, fluorescence resonance energy transfer (FRET), Fourier transform infrared (FTIR), and circular dichroism (CD) spectroscopy), electrochemistry (cyclic voltammetry), and computational methods (molecular docking and molecular dynamic simulation). The steady-state fluorescence results showed that fluorescence intensity of HSA decreased in the presence of NOS via a static quenching mechanism, which involves ground state complex formation between NOS and HSA. UV-visible and FRET results also supported the fluorescence result. The corresponding thermodynamic result shows that binding of NOS with HSA is exothermic in nature, involving electrostatic interactions as major binding forces. The binding results were further confirmed through a cyclic voltammetry approach. The FRET result signifies the energy transfer from Trp214 of HSA to the NOS. Molecular site marker, molecular docking, and MD simulation results indicated that the principal binding site of HSA for NOS is site I. Synchronous fluorescence spectra, FTIR, 3D fluorescence, CD spectra, and MD simulation results reveal that NOS induced the structural change in HSA. In addition, the MTT assay study on a human skin cancer cell line (A-431) was also performed for NOS, which shows that NOS induced 80% cell death of the population at a 320 μM concentration. Moreover, the esterase-like activity of HSA with NOS was also done to determine the variation in protein functionality after binding with NOS.

Noscapine may cause pain

Noscapine may cause pain

Nanoparticles Based on Linear and Star-Shaped Poly(Ethylene Glycol)-Poly(ε-Caprolactone) Copolymers for the Delivery of Antitubulin Drug.

Biodegradable polymeric nanoparticles of different architectures based on polyethylene glycol-co-poly(ε-caprolactone) block copolymers have been loaded with noscapine (NOS) to study their effect on its anticancer activity. It was intended to use solubility of NOS in an acidic environment and ability of the nanoparticles to passively target drugs into cancer tissue to modify the NOS pharmacokinetic properties and reduce the requirement for frequent injections. Linear and star-shaped copolymers were synthetized and used to formulate NOS loaded nanoparticles. Cytotoxicity was performed using a sulforhodamine B method on MCF-7 cells, while biocompatibility was determined on rats followed by hematological and histopathological investigations. Formulae with the smallest particle sizes and adequate entrapment efficiency revealed that NOS loaded nanoparticles showed higher extent of release at pH4.5. Colloidal stability suggested that nanoparticles would be stable in blood when injected into the systemic circulation. Loaded nanoparticles had IC50 values lower than free drug. Hematological and histopathological studies showed no difference between treated and control groups. Pharmacokinetic analysis revealed that formulation P1 had a prolonged half-life and better bioavailability compared to drug solution. Formulation of NOS into biodegradable polymeric nanoparticles has increased its efficacy and residence on cancer cells while passively avoiding normal body tissues. Graphical Abstract ᅟ.

Combination of electrochemistry with chemometrics to introduce an efficient analytical method for simultaneous quantification of five opium alkaloids in complex matrices

For the first time, an analytical methodology based on differential pulse voltammetry (DPV) at a glassy carbon electrode (GCE) and integration of three efficient strategies including variable selection based on ant colony optimization (ACO), mathematical pre-processing selection by genetic algorithm (GA), and sample selection (SS) through a distance-based procedure to improve partial least squares-1 (PLS-1, ACO-GA-SS-PLS-1) multivariate calibration (MVC) for the simultaneous determination of five opium alkaloids including morphine (MOP), noscapine (NOP), thebaine (TEB), codeine (COD), and papaverine (PAP) was used and validated. The baselines of the DPV signals were modeled as a smooth curve, using P-splines, a combination of B-splines and a discrete roughness penalty. After subtraction of the baseline we got a signal with a two-component probability density. One component was for the peaks and it was approximated by a uniform distribution on the potential axis. The other component was for the observed noise around the baseline. Some sources of bi-linearity deviation for electrochemical data were discussed and analyzed. The lack of bi-linearity was tackled by potential shift correction using correlation optimized warping (COW) algorithm. The MVC model was developed as a quinternary calibration model in a blank human serum sample (drug-free) provided by a healthy volunteer to regard the presence of a strong matrix effect which may be caused by the possible interferents present in the serum, and it was validated and tested with two independent sets of analytes mixtures in the blank and actual human serum samples, respectively. Fortunately, the proposed methodology was successful in simultaneous determination of MOP, NOP, TEB, COD, and PAP in both blank and actual human serum samples and its results were satisfactory comparable to those obtained by applying the reference method based on high performance liquid chromatography-ultraviolet detection (HPLC-UV).

Synergistic suppression of noscapine and conventional chemotherapeutics on human glioblastoma cell growth

Noscapine (NOS) is a non-narcotic opium alkaloid with anti-tumor activity. The aim of this study was to investigate the effects of the combination of NOS with conventional chemotherapeutics temozolamide (TMZ), bis-chloroethylnitrosourea (BCNU), or cisplatin (CIS)on human glioblastoma cells. U87MG human glioblastoma cells were examined. Cell proliferation was quantified using MTT assay. Western blotting and flow cytometry were used to examine apoptosis and the expression of active caspase-3 and cleaved PARP. Mouse tumor xenograft model bearing U87MG cells was treated with TMZ (2 mg·kg(-1)·d(-1), ip) or CIS (2 mg/kg, ip 3 times a week) alone or in combination with NOS (200 mg·kg(-1)·d(-1), ig) for 3 weeks. Immunohistochemistry was used to investigate the expression of active caspase-3 and Ki67 following treatment in vivo. The safety of the combined treatments was evaluated based on the body weight and histological studies of the animal's organs. NOS (10 or 20 mol/L) markedly increased the anti-proliferation effects of TMZ, BCNU, and CIS on U87MG cells in vitro. The calculated combination index (CI) values of NOS-CIS, NOS-TMZ, and NOS-BCNU (20 μmol/L) were 0.45, 0.51, and 0.57, respectively, demonstrating synergistic inhibition of the drug combinations. In tumor xenograft models, combined treatment with NOS robustly augmented the anti-cancer actions of TMZ and CIS, and showed no detectable toxicity. The combined treatments significantly enhanced the apoptosis, the activated caspase-3 and PARP levels in U87MG cells in vitro, and reduced Ki67 staining and increased the activated caspase-3 level in the shrinking xenografts in vivo. NOS synergistically potentiated the efficacy of FDA-approved anti-cancer drugs against human glioblastoma cells, thereby allowing them to be used at lower doses and hence minimizing their toxic side effects.