A synthesis, in silico, in vitro and in vivo study of thieno[2,3-b]pyridine anticancer analogues

A synthesis, in silico, in vitro and in vivo study of thieno[2,3-b]pyridine anticancer analogues Full article

Journal

MedChemComm
ISSN: 2040-2503 , E-ISSN: 2040-2511

Output data

Year: 2015, Volume: 6, Number: 11, Pages: 1987-1997 Pages count : DOI: 10.1039/c5md00245a

Authors

Arabshahi Homayon J. ¹ , van Rensburg Michelle ¹ , Pilkington Lisa I. ^1,2,3 , Jeon Chae Yeon ¹ , Song Mirae ¹ , Gridel Ling-Mey ¹ , Leung Euphemia ^2,3 , Barker David ¹ , Vuica-Ross Milena ⁴ , Volcho Konstantin P. ^5,6 , Zakharenko Alexandra L. ⁷ , Lavrik Olga I. ^6,7 , Reynisson Johannes ¹

Affiliations

1	(Данные Web of science) Univ Auckland, Sch Chem Sci, Auckland 1142, New Zealand
2	(Данные Web of science) Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1142, New Zealand
3	(Данные Web of science) Univ Auckland, Dept Mol Med & Pathol, Auckland 1142, New Zealand
4	(Данные Web of science) Johns Hopkins Univ, Sch Med, Baltimore, MD USA
5	(Данные Web of science) Russian Acad Sci, NN Vorozhtsov Novosibirsk Inst Organ Chem, Siberian Branch, Novosibirsk, Russia
6	(Данные Web of science) Novosibirsk State Univ, Novosibirsk 630090, Russia
7	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Russia

The anticancer activity of the thieno[2,3-b]pyridines was explored by altering the ring size of the cyclo-aliphatic moiety. Five-, six-, seven- and eight-membered derivatives were tested against the NCI60 tumour cell panel. According to this assay the most active derivative 9a has a cyclooctane moiety, which suggests that larger aliphatic ring systems are favourable. For the most sensitive tumour cell line MB-MDA-435, derivative 9a has a GI(50) = 70 nM and a LC50 = 925 nM. To explore the biological mechanism of the thieno-[2,3- b]pyridines five derivatives were tested against tyrosyl-DNA phosphodiesterase I (TDP1), a phospholipase D enzyme, using a biochemical assay. The most potent derivative for TDP1 was 9d, giving an excellent IC50 at 0.5 +/- 0.1 mu M. Also, derivative 12 was tested against 97 kinases and no or very limited activity was found, excluding this class of biomolecular targets. Finally, a mouse xenograft study using derivative 12 was encouraging but the tumour size/mass reduction was not quite statistically significant.

Arabshahi H.J. , van Rensburg M. , Pilkington L.I. , Jeon C.Y. , Song M. , Gridel L-M. , Leung E. , Barker D. , Vuica-Ross M. , Volcho K.P. , Zakharenko A.L. , Lavrik O.I. , Reynisson J.
A synthesis, in silico, in vitro and in vivo study of thieno[2,3-b]pyridine anticancer analogues
MedChemComm. 2015. V.6. N11. P.1987-1997. DOI: 10.1039/c5md00245a WOS Scopus РИНЦ OpenAlex

Web of science:	WOS:000364154000009
Scopus:	2-s2.0-84946556864
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Web of science	48
Scopus	43
Elibrary	46
OpenAlex	50