Induction of microtubule hyper stabilization and robust G /M arrest by N-4-CN in human breast carcinoma MDA-MB-231 cells.

Aim: Elucidation of the antiproliferative efficacy and mechanism of action of a design-optimized noscapine analog, N-4-CN.

Methods: Cell viability was studied using an MTT assay. The drug-tubulin interactions were investigated using spectrofluorometry.

Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents.

We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity.

Synthesis and biological evaluation of novel biaryl type α-noscapine congeners.

Natural α-noscapine, a known antitussive drug, is also now known to possess weak anticancer efficacy with relatively safe toxicity profile. In this study, we report synthesis and evaluation of novel biaryl type α-noscapine congeners designed by adding aryl unit to the tetrahydroisoquinoline part of natural α-noscapine core. Palladium catalyzed Suzuki cross coupling of 9-bromo α-noscapine with aryl boronic acids was employed using mild and inexpensive reagents to attain desired noscapinoids 5a-g in excellent yields.

Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.

Copper(I) mediated facile synthesis of potent tubulin polymerization inhibitor, 9-amino-α-noscapine from natural α-noscapine.

Facile synthesis of natural α-noscapine analogue, 9-amino-α-noscapine, a potent inhibitor of tubulin polymerization for cancer therapy, is achieved via copper(I) iodide mediated in situ aromatic azidation and reduction of 9-bromo-α-noscapine (obtained by bromination of natural α-noscapine) with NaN(3) in DMSO at 130°C in the presence of L-proline as an amino acid promoter. The protocol developed here avoided isolation of 9-azido-α-noscapine and did not cleave the sensitive C-C bond between two heterocyclic phthalide and isoquinoline units.