54383-36-7Relevant articles and documents
1,3-Benzodioxole-Modified Noscapine Analogues: Synthesis, Antiproliferative Activity, and Tubulin-Bound Structure
Yong, Cassandra,Devine, Shane M.,Abel, Anne-Catherine,Tomlins, Stefan D.,Muthiah, Divya,Gao, Xuexin,Callaghan, Richard,Steinmetz, Michel O.,Prota, Andrea E.,Capuano, Ben,Scammells, Peter J.
, p. 2882 - 2894 (2021/07/19)
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 to the 1,3-benzodioxole moiety. This includes expansion of the dioxolane ring and inclusion of metabolically robust deuterium and fluorine atoms. Favourable structural modifications were subsequently incorporated into multi-functionalised noscapine derivatives that also possessed modifications previously shown to promote anti-proliferative activity in the 1-, 6′- and 9′-positions. Our research efforts afforded the deuterated noscapine derivative 14 e and the dioxino-containing analogue 20 as potent cytotoxic agents with EC50 values of 1.50 and 0.73 μM, respectively, against breast cancer (MCF-7) cells. Compound 20 also exhibited EC50 values of ADR/RES). We also conducted X-ray crystallography studies that yielded the high-resolution structure of 14 e bound to tubulin. Our structural analysis revealed the key interactions between this noscapinoid and tubulin and will assist with the future design of noscapine derivatives with improved properties.
The synthesis and biological evaluation of multifunctionalised derivatives of noscapine as cytotoxic agents
DeBono, Aaron J.,Mistry, Sarah J.,Xie, Jinhan,Muthiah, Divya,Phillips, Jackson,Ventura, Sabatino,Callaghan, Richard,Pouton, Colin W.,Capuano, Ben,Scammells, Peter J.
, p. 399 - 410 (2014/04/03)
Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well-known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, effor
Stereochemical elucidation of the reaction products of α-narcotine with ethyl chloroformate
Lee,Eibler,Mayer,Wiegrebe
, p. 1995 - 1997 (2007/10/03)
α-Narcotine (1) was treated with ethyl chloroformate by refluxing in dichloromethane to afford six products, which were separated by preparative high-performance liquid chromatography (HPLC). Their stereochemistry and structures were elucidated. This reaction proceeded initially to the chloro- carbamates and successively to the corresponding carbinols. In addition, N- desmethyl-N-carbethoxynarcotine (3), found in the HPLC chromatogram, was identified by direct comparison with synthetic 3; this compound had caused difficulty in our previous mass spectrometric investigations.
STUDY OF CONFORMATION OF α-NARCOTINE N-OXIDE AND RELATED COMPOUNDS
Uhrin, Dusan,Proksa, Bohumil
, p. 498 - 505 (2007/10/02)
Conformation of quaternary derivatives of (-)-α-narcotine (I) in solution was investigated using α-narcotine N-oxide hydrochloride (IV) as the compound.In solution, compound IV exists predominantly in the form with torsion angle H-C(1)-C(9)-H of about 270 deg and with half-chair conformation of the isoquinoline tetrahydropyridine ring.
