1,3‐Benzodioxole‐Modified Noscapine Analogues: Synthesis, Antiproliferative Activity, and Tubulin‐Bound Structure

@article{Yong202113BenzodioxoleModifiedNA,
  title={1,3‐Benzodioxole‐Modified Noscapine Analogues: Synthesis, Antiproliferative Activity, and Tubulin‐Bound Structure},
  author={Cassandra Yong and Shane M. Devine and Anne‐Catherine Abel and Stefan Dominic Tomlins and Divya Muthiah and Xuexin Gao and Richard Callaghan and Michel O. Steinmetz and Andrea E. Prota and Ben Capuano and Peter J. Scammells},
  journal={ChemMedChem},
  year={2021},
  volume={16}
}
Since the revelation of noscapine's weak anti‐mitotic activity, extensive research has been conducted over the past two decades, with the goal of discovering noscapine derivatives with improved potency. To date, noscapine has been explored at the 1, 7, 6′, and 9′‐positions, though the 1,3‐benzodioxole motif in the noscapine scaffold that remains unexplored. The present investigation describes the design, synthesis and pharmacological evaluation of noscapine analogues consisting of modifications… 

References

SHOWING 1-10 OF 41 REFERENCES
The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents
TLDR
The synthesis of a series of noscapine analogues, which have been modified in the 6′, 9′, 1 and 7‐positions, exhibited the most promising biological activities, with EC50 values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.
Synthesis and Biological Evaluation of N‐Substituted Noscapine Analogues
TLDR
The synthesis and pharmacological evaluation of a series of 6′‐substituted noscapine derivatives found to possess microtubule‐modulating properties and anticancer activity and to inhibit cell proliferation was reported.
A Novel Class of N‐Sulfonyl and N‐Sulfamoyl Noscapine Derivatives that Promote Mitotic Arrest in Cancer Cells
TLDR
Advances in this area are described, namely the synthesis and pharmacological evaluation of a series of N‐sulfonyl and N‐ sulfamoyl noscapine derivatives, a number of which demonstrated improved activities compared to nos capine.
Synthesis and Pharmacological Evaluation of Noscapine-Inspired 5-Substituted Tetrahydroisoquinolines as Cytotoxic Agents.
TLDR
Insight is provided into structural modifications to noscapine that will guide future development toward more potent cytotoxic agents that are active against resistant cancer cells and, in combination studies, potentiate the antiproliferative activity of vinblastine.
Rational Design of Novel Anti-microtubule Agent (9-Azido-Noscapine) from Quantitative Structure Activity Relationship (QSAR) Evaluation of Noscapinoids
TLDR
To obtain systematic insight into the relationship between the structural framework of noscapine scaffold and its antitumor activity, the authors synthesized strategic derivatives (including two new ones in this article) that turned out to be very close to predicted pIC50.
A new antiproliferative noscapine analogue: chemical synthesis and biological evaluation
TLDR
This novel compound has a more potent cytotoxic effect on cancer cell lines than its parent, noscapine, and hence should be of interest as a potential anti-cancer drug.
Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents.
TLDR
A number of noscapine analogues possessing various modifications have been described within the literature and have shown significantly improved antiprolific profiles for a large variety of cancer cell lines.
Development of a Novel Nitro-Derivative of Noscapine for the Potential Treatment of Drug-Resistant Ovarian Cancer and T-Cell Lymphoma
TLDR
9-nitro-nos has great potential to be a novel therapeutic agent for ovarian and T-cell lymphoma cancers, even those that have become drug-resistant to currently available chemotherapeutic drugs.
Rational design, synthesis and biological evaluations of amino-noscapine: a high affinity tubulin-binding noscapinoid
TLDR
The ‘blind docking’ approach as well as the reasonable accuracy of calculating ΔGbind using LIE–SGB model constitutes the first evidence that this class of compounds binds to tubulin at a site overlapping with colchicine-binding site or close to it.
...
...