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Noscapine is an isolated compound from the opium poppy, with distinctive chiral structure and chemistry, interacts with other compounds due to having multiple π-acceptors, hydrogen bond acceptors, and ionic sites. Therefore, it has promising applicability for the enantioselective separation of a wide range of polar, acidic, basic, and neutral compounds. A new noscapine derivative chiral stationary phase (ND-CSP) has been synthesized by consecutive N-demethylation, reduction, and N-propargylation of noscapine followed by attachment of a solid epoxy-functionalized silica bed through the 1,3-dipolar Huisgen cycloaddition. The noscapine derivative-based stationary phase provides a considerable surface coverage, which is greater than some commercial CSPs and can validate better enantioresolution performance. The major advantages inherent to this chiral selector are stability, reproducibility after more than 200 tests, and substantial loading capacity. The characterization by Fourier transform infrared (FTIR) spectroscopy and elemental analysis indicated successful functionalization of the silica surface. Chromatographic method conditions like flow rate and mobile phase composition for enantioseparation of various compounds such as warfarin, propranolol, mandelic acid, and a sulfanilamide derivative were optimized. Comparing the experimental results with docking data revealed a clear correlation between the calculated binding energy of ND-CSP and each enantiomer with the resolution of enantiomer peaks., (© 2022 Wiley Periodicals LLC.)

Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z' > 0.7). The screening resulted in the identification of two novel noscapine derivatives as inhibitors of MDA cell growth with IC 50 values of 5 µM and 1.5 µM, respectively. Both hit molecules have a five-fold and seventeen-fold higher potency, compared with that of lead compound noscapine (IC 50 26 µM). The identified active derivatives retain the tubulin-binding ability of noscapine. Further testing of both hit molecules, alongside the natural product against additional cancer cell lines (HepG2, HeLa and PC3 cells) confirmed our initial findings. Both molecules have improved anti-proliferative properties when compared to the initial natural product, noscapine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Twenty novel 1,2,3-triazole noscapine derivatives were synthesized starting from noscapine by consecutive N-demethylation, reduction of lactone ring, N-propargylation and Huisgen 1,3-dipolar cycloaddition reaction. In order to select the most promising molecules to subject to further biophysical and biological evaluation, a molecular docking analysis round was performed using noscapine as reference compound. The molecules featuring docking predicted binding affinity better than that of noscapine were then subjected to MTT assay against MCF7 cell line. The obtained results disclosed that all the selected triazole derivatives exhibited a remarkably lower cell viability compared to noscapine in the range of 20 μM in 48 h. In an attempt to correlate the biological activity with the ability to bind tubulin, the surface plasmon resonance (SPR) assay was employed. Compounds 8a, 8h, 9c, 9f and 9j were able to bind tubulin with affinity constant values in the nanomolar range and higher if compared to noscapine. Integrating computational predictions and experimental evaluation, two promising compounds (8h and 9c) were identified, whose relevant cytotoxicity was supposed to be correlated with tubulin binding affinity. These findings shed lights onto structural modifications of noscapine toward the identification of more potent cytotoxic agents targeting tubulin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Novel N-substituted noscapine derivatives were synthesized by a three-component Strecker reaction of cyclic ether of N-nornoscapine with varied aldehydes, in the presence of cyanide ion. Moreover, the corresponding amides were synthesized by the oxidation of cyanide moieties in good yields. The in vitro antiprotozoal activity of the products was also investigated. Interestingly, some analogues did put on display promising antiparasitic activity against Trypanosoma brucei rhodesiense with IC 50 values between 2.5 and 10.0 µM and selectivity index (SI) ranged from 0.8 to 13.2. Eight compounds exhibited activity against Plasmodium falciparum K1 strain with IC 50 ranging 1.7-6.4 µM, and SI values between 2.8 and 10.5 against L6 rat myoblast cell lines. 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 2 and 6b 2 displayed excellent docking scores with -8.59 and -8.86 kcal/mol for TbTR and TbUDPGE, respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Noscapine, a natural alkaloid, has never been used as a parent scaffold in chiral induction. The first examples of noscapinoid compounds as efficient catalysts in asymmetric synthesis are now reported. Three derivatives of noscapine were synthesized from its reaction with different Grignard reagents. Asymmetric addition of diethylzinc to aldehydes was performed in the presence of these catalysts in high yields and good to excellent ees. [ABSTRACT FROM AUTHOR]

In this paper, synthesis of two derivatives of noscapine and their application as organocatalysts in the asymmetric addition of diethylzinc to aromatic aldehydes is reported. The first catalyst ( 2) was synthesized by the reduction of lactone ring of noscapine to form the corresponding diol, and the second one ( 3) was prepared by tert-butyl dimethyl silylation of the primary hydroxyl group of 2. Excellent yields and high ees up to 95% were obtained by using 3 as the catalyst. To the best of our knowledge, this is the first report on the application of lactone ring opened noscapinoid compounds as organocatalysts in asymmetric reactions. [ABSTRACT FROM AUTHOR]

Novel isothiocyanate derivatives were synthesized starting from noscapine, bile acids, amino acids, and some aromatic compounds. Antiparasitic activities of the synthesized derivatives were tested against four unicellular protozoa, i.e. , Trypanosoma brucei rhodesiense , T. cruzi , Leishmania donovani, and Plasmodium falciparum. Interestingly, seven isothiocyanate analogues displayed promising antiparasitic activity against Leishmania donovani with IC 50 values between 0.4 and 1.0 µM and selectivity index (SI) ranged from 7.8 to 18.4, comparable to the standard drug miltefosine (IC 50 = 0.7 μM). Compound 7h demonstrated the best antileishmanial activity with an IC 50 value of 0.4 µM. Seven products exhibited inhibition activity against T. brucei rhodesiense with IC 50 s below 2.0 μM and SI between 2.7 and 29.3. Four primary amine derivatives of noscapine and five isothiocyanate derivatives exhibited antiplasmodial activity with IC 50 s in the range of 1.1–2.7 µM and SI values between 1.1 and 14.5. The isothiocyanate derivative 7c showed against T. cruzi with an IC 50 value of 1.9 µM and SI 4. Molecular docking and ADMET studies were performed to investigate the interaction between active ligands and T. brucei trypanothione reductase active site. The docking studies showed significant binding affinity of noscapine derivatives to enzyme active site and good compatibility with experimental data. [ABSTRACT FROM AUTHOR]