- 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
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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.
- Eurtivong, Chatchakorn,Semenov, Victor,Semenova, Marina,Konyushkin, Leonid,Atamanenko, Olga,Reynisson, Jóhannes,Kiselyov, Alex
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p. 658 - 664
(2016/12/27)
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- Synthesis and antiproliferative activity of 2-chlorophenyl carboxamide thienopyridines
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3-Amino-2-arylcarboxamide-thieno[2,3-b]pyridines are a known class of antiproliferative compounds with activity against the phospholipase C enzyme. To further investigate the structure activity relationships of these derivatives a series of analogues were prepared modifying key functional groups. It was determined that modification of the 3-amino and 2-aryl carboxamide functionalities resulted in complete elimination of activity, whilst modification at C-5 allowed compounds of greater activity to be prepared.
- van Rensburg, Michelle,Leung, Euphemia,Haverkate, Natalie A.,Eurtivong, Chatchakorn,Pilkington, Lisa I.,Reynisson, Jóhannes,Barker, David
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supporting information
p. 135 - 138
(2016/12/27)
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- Synthesis and cytotoxicity of thieno[2,3-b]quinoline-2-carboxamide and cycloalkyl[b]thieno[3,2-e]pyridine-2-carboxamide derivatives
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Seventy nine derivatives of thieno[2,3-b]quinolines, tetrahydrothieno[2,3-b]quinoline, dihydrocyclopenta[b]thieno[3,2-e]pyridine, cyclohepta[b]thieno[3,2-e]pyridine and hexahydrocycloocta[b]thieno[3,2-e]pyridine were either synthesized or obtained commercially and tested for their antiproliferative activity against HCT116, MDA-MB-468 and MDA-MB-231 human cancer cell lines. The most potent eight compounds were active against all cell lines with IC50 values in the 80–250 nM range. In general hexahydrocycloocta[b]thieno[3,2-e]pyridines were most active with increasing activity observed as larger cycloalkyl rings were fused to the pyridine ring.
- Leung, Euphemia,Pilkington, Lisa I.,van Rensburg, Michelle,Jeon, Chae Yeon,Song, Mirae,Arabshahi, Homayon J.,De Zoysa, Gayan Heruka,Sarojini, Vijayalekshmi,Denny, William A.,Reynisson, Jóhannes,Barker, David
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supporting information
p. 1142 - 1154
(2019/05/24)
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- Synthesis of some thienotetrahydroquinoline derivatives
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2-Thioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (2) was easily S-alkylated to produce alkyl mercapto derivatives 3a-g. The latter compounds were cyclized to afford thienotetrahydroquinolines 4a-g. Several pyrimidothienotetrahydroquinolines 5a-d, and 6a-d were obtained from the condensation of compounds 4c-f with different reagents. o-Aminocarbohydrazide derivative 11 was reacted with aromatic aldehydes, acetylacetone, nitrous acid and CS2 to afford compounds 12-15. Compound 24 was coupled with aryldiazonium chloride to afford arylazo derivatives 25. Also it condensed with aromatic aldehydes to give arylidene derivatives 26. The latter compounds were reacted with malononitrile to give pyrano derivative 27.
- Kamal El-Dean,Shaker,Abo El-Hassan,Abdel Latif
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p. 335 - 345
(2007/10/03)
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- Synthesis of some thienotetrahydroquinoline derivatives
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2-Thioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (2) was easily S-alkylated to produce alkyl mercapto derivatives 3a-g. The latter compounds were cyclized to afford thienotetrahydroquinolines 4a-g. Several pyrimidothienotetrahydroquinolines 5a-d, and 6a-d were obtained from the condensation of compounds 4c-f with different reagents. o-Aminocarbohydrazide derivative 11 was reacted with aromatic aldehydes, acetylacetone, nitrous acid and CS2 to afford compounds 12-15. Compound 24 was coupled with aryldiazonium chloride to afford arylazo derivatives 25. Also it condensed with aromatic aldehydes to give arylidene derivatives 26. The latter compounds were reacted with malononitrile to give pyrano derivative 27.
- Kamal El-Dean,Shaker,Abo El-Hassan,Abdel Latif
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p. 335 - 345
(2015/02/02)
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- A synthetic strategy to a new class of cycloalkane ring-fused pyridine nucleosides as potential anti HIV agents
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Condensation of cyanothioacetamide or cyanoacetamide with sodium salts of 2-formyl-1-cycloalkanones afforded the corresponding cycloalkane ring fused pyridine-2(1H)-thiones and -2-pyridones. The latter compounds served as a key intermediates for the synthesis of a new class of cycloalkane ring fused pyridine glycosides.
- Elgemeie, Galal E. H.,Attia, Adel M. E.,Hussain, Badria A. W.
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p. 855 - 868
(2007/10/03)
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- A convenient synthesis of 5-deaza nonclassical antifolates: Reaction of cyanothioacetamide with sodium salts of 2-(hydroxymethylene)-1-cycloalkanones
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Condensation of cyanothioacetamide with sodium salts of 2-(hydroxymethylene)-1-cycloalkanones afforded the corresponding pyridine-2(1H)-thiones 4. Compounds 4 served as a key intermediate for the synthesis of condensed 2,4-diaminopyrido[2,3-d]pyridines 7. Compounds 7 were of interest as potential inhibitors of dihydrofolate reductase.
- Elgemeie, Galal E. H.,Hussain, Badria A. W.
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p. 199 - 204
(2007/10/02)
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