Реферат: A series of 3-amino-thieno[2,3-b]pyridines was prepared and tested in a phenotypic sea urchin embryo assay to identify potent and specific molecules that affect tubulin dynamics. The most active compounds featured a tricyclic core ring system with a fused cycloheptyl or cyclohexyl substituent and unsubstituted or alkyl-substituted phenyl moiety tethered via a carboxamide. Low nano-molar potency was observed in the sea urchin embryos for the most active compounds (1–5) suggestive of a microtubule-destabilising effect. The molecular modelling studies indicated that the tubulin colchicine site is inhibited, which often leads to microtubule-destabilisation in line with the sea urchin embryo results. Finally, the identified hits displayed a robust growth inhibition (GI50 of 50–250 nM) of multidrug-resistant melanoma MDA-MB-435 and breast MDA-MB-468 human cancer cell lines. This work demonstrates that for the thieno[2,3-b]pyridines the most effective mechanism of action is microtubule-destabilisation initiated by binding to the colchicine pocket.

Библиографическая ссылка: Eurtivong C. , Semenov V. , Semenova M. , Konyushkin L. , Atamanenko O. , Reynisson J. , Kiselyov A.
3-Amino-thieno[2,3-b]pyridines as microtubule-destabilising agents: Molecular modelling and biological evaluation in the sea urchin embryo and human cancer cells
Bioorganic & Medicinal Chemistry. 2017. V.25. N2. P.658-664. DOI: 10.1016/j.bmc.2016.11.041 WOS Scopus OpenAlex

Идентификаторы БД:

Web of science:	WOS:000392906500021
Scopus:	2-s2.0-85006857277
OpenAlex:	W2557465420

Цитирование в БД:

БД	Цитирований
OpenAlex	40
Scopus	38
Web of science	37

Альметрики: