Tubulin binding, protein-bound conformation in solution, and antimitotic cellular profiling of noscapine and its derivatives.
Noscapine and its 7-hydroxy and 7-amino derivatives were characterized for their binding to tubulin. A solution NMR structure of these compounds bound to tubulin shows that noscapine and its 7-aniline derivative do not compete for the same binding site nor does its small molecule crystal structure match its tubulin-bound conformation. These compounds were also tested for their antiproliferative effects on a panel hepatocellular carcinoma cell lines.
Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge Massachusetts 02139, USA. youssef_Bennani@vrtx.com
Youssef L
YL
Bennani
Wenxin
W
Gu
Angeles
A
Canales
Fernando J
FJ
Díaz
Brenda K
BK
Eustace
Russell R
RR
Hoover
Jesus
J
Jiménez-Barbero
Azin
A
Nezami
Tiansheng
T
Wang
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005453:Fluorescence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009665:Noscapine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D012996:Solutions; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry*; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D012996:Solutions; D014404:Tubulin; D050257:Tubulin Modulators; D009665:Noscapine