当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, selective alkylation and X-ray crystal structure determination of dihydro-indolyl-1,2,4-triazole-3-thione and its 3-benzylsulfanyl analogue as potent anticancer agents.

Design, selective alkylation and X-ray crystal structure determination of dihydro-indolyl-1,2,4-triazole-3-thione and its 3-benzylsulfanyl analogue as potent anticancer agents.

Abstract：

:Three sets of substituted indolyl-triazoles were synthesized by the alkylation of 1,2-dihydro-5-(1H-indol-2-yl)-1,2,4-triazole-3-thione with different alkyl halides. The use of pyridine restricted the alkylation to sulfur. Whereas, upon using K2CO3, the alkylation exceeded sulfur to one of the remaining triazole nitrogens. The assignment of which nitrogen is alkylated besides sulfur is made for the first time using X-ray analysis of single crystals and 2D NMR which indicated that S-, 2-N-isomers will be preferably formed over the S-, 1-N-isomers. The antiproliferative activity on HEPG-2 and MCF-7 cancer cell lines was tested. The results showed that compound 2a is the most active with an IC50 3.58 μg/mL and 4.53 μg/mL for HEPG-2 and MCF-7 respectively and compound 7 is the least active with an IC50 > 100 μg/mL compared to the standard drug doxorubicin (IC50 4.0 μg/mL). The interaction of the synthesized compounds with tyrosine kinases, namely, Akt, PI3, and EGFR was also studied using molecular docking simulation to predict their mode of action which will drive future work directions.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Boraei AT,Gomaa MS,El Ashry ES,Duerkop A

doi

10.1016/j.ejmech.2016.09.046

subject

Has Abstract

pub_date

2017-01-05 00:00:00

pages

360-371

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)30784-X

journal_volume

125

pub_type

杂志文章

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