3395-04-8Relevant academic research and scientific papers
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
Eurtivong, Chatchakorn,Semenov, Victor,Semenova, Marina,Konyushkin, Leonid,Atamanenko, Olga,Reynisson, Jóhannes,Kiselyov, Alex
, p. 658 - 664 (2016/12/27)
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 (GI50of 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.
Synthesis of N-glycosylated pyridines as new antimetabolite agents
Hussain, Badria A.,Attia, Adel M.,Elgemeie, Galal E. H.
, p. 2335 - 2343 (2007/10/03)
Condensation of cyanoacetamide and cyanothioacetamide with the sodium salts of α-(hydroxymethylene)alkanones afforded the pyridine-2(1H)-ones and their corresponding thiones 3. Compounds 3 served as a key intermediates for the synthesis of N-glycosylated pyridines.
