Boraei, Ahmed T. A. and Gomaa, Mohamed S. and El Ashry, El Sayed H. and Duerkop, Axel (2017) 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. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 125. pp. 360-371. ISSN 0223-5234, 1768-3254
Full text not available from this repository. (Request a copy)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 mu g/mL and 4.53 mu g/mL for HEPG-2 and MCF-7 respectively and compound 7 is the least active with an IC50 > 100 mu g/mL compared to the standard drug doxorubicin (IC50 4.0 mu g/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. (C) 2016 Elsevier Masson SAS. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BREAST-CANCER CELLS; DRUG LEADS; INDOLE; REGIOSELECTIVITY; BENGACARBOLINE; CYTOTOXICITY; Anticancer activity; HEPG-2; MCF-7; 1,2,4-Triazolethiones; Selectivity; Alkylation |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:01 |
| Last Modified: | 14 Feb 2019 09:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/575 |
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