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.

Autor: Boraei AT; Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt. Electronic address: Ahmed_tawfeek83@yahoo.com., Gomaa MS; Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt., El Ashry ES; Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt., Duerkop A; Institute of Analytical Chemistry, Chemo and Biosensors, Universitätsstrasse 31, 93053 Regensburg, Germany.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2017 Jan 05; Vol. 125, pp. 360-371. Date of Electronic Publication: 2016 Sep 15.
DOI: 10.1016/j.ejmech.2016.09.046
Abstrakt: 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 K 2 CO 3 , 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 IC 50  > 100 μg/mL compared to the standard drug doxorubicin (IC 50 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.
(Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: