Design, synthesis and pharmaco-toxicological assessment of 5-mercapto-1,2,4-triazole derivatives with antibacterial and antiproliferative activity

Mioc,Marius; Soica,Codruta; Bercean,Vasile; Avram,Sorin; Balan‑Porcarasu,Mihaela; Coricovac,Dorina; Ghiulai,Roxana; Muntean,Delia; Andrica,Florina; Dehelean,Cristina; Spandidos,Demetrios  A.; Tsatsakis,Aristides  M.; Kurunczi,Ludovic

doi:10.3892/ijo.2017.3912

Design, synthesis and pharmaco-toxicological assessment of 5-mercapto-1,2,4-triazole derivatives with antibacterial and antiproliferative activity

Authors:
- Marius Mioc
- Codruta Soica
- Vasile Bercean
- Sorin Avram
- Mihaela Balan‑Porcarasu
- Dorina Coricovac
- Roxana Ghiulai
- Delia Muntean
- Florina Andrica
- Cristina Dehelean
- Demetrios A. Spandidos
- Aristides M. Tsatsakis
- Ludovic Kurunczi
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Affiliations: Faculty of Pharmacy, ‘Victor Babes’ University of Medicine and Pharmacy, Timisoara 300041, Romania, S.C. SINOFIN S.R.L., Timisoara 300544, Romania, Department of Computational Chemistry, Institute of Chemistry Timisoara of the Romanian Academy, Timisoara 300223, Romania, Institute of Macromolecular Chemistry ‘Petru Poni’, Iasi 700487, Romania, Faculty of Medicine, Victor Babes’ University of Medicine and Pharmacy, Timisoara 300041, Romania, Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71409, Greece, Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003, Greece
Published online on: March 14, 2017 https://doi.org/10.3892/ijo.2017.3912
Pages: 1175-1183
Copyright: © Mioc et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The extensive biochemical research of multiple types of cancer has revealed important enzymatic signaling pathways responsible for tumor occurrence and progression, thus compelling the need for the discovery of new means with which to block these signaling cascades. The phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT) pathway, which plays an important role in maintaining relevant cellular functions, exhibits various alterations in common human cancers, thus representing a suitable target in cancer treatment. Molecules bearing the 1,2,4-triazole moiety are known to possess multiple biological activities, including anticancer activity. The current study used molecular docking in the design of 5-mercapto-1,2,4-triazole derivatives with antiproliferative activity targeting the PI3K/AKT pathway. Three structures emerged as the result of this method, which indicated for these a highly favorable accommodation within the active binding site of PI3K protein, thus acting as potential PI3K inhibitors, and hence interfering with the above-mentioned pathway. The molecules were synthesized and their chemical structure was confirmed. The antiproliferative activity of these compounds was tested on 4 cancer cell lines (A375, B164A5, MDA-MB-231 and A549) and on normal human keratinocytes (HaCaT) by in vitro alamarBlue assay. The 3 compounds revealed antitumor activity against the breast cancer cell line (MDA-MB-231) and reduced toxicity on the normal cell line. The antibacterial activity of the compounds was also tested in vitro on Gram-positive and Gram-negative bacterial strains, revealing moderate activity.

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