Bazı Antidepresanların Antikanser Hedefi Olan Tioredoksin Redüktaz Enziminin İnhibitörleri Olarak Değerlendirilmesi

Öz

Tioredoksin redüktaz (TrxR), tioredoksinin indirgenmesini katalize ederek detoksifikasyondan radikallerin indirgenmesine kadar pek çok metabolik yolda yer almaktadır. Bu nedenle kanser de dahil olmak üzere birçok fizyolojik süreçle ilişkili bir enzimdir. Bu enzimin inhibitörleri antikanser hedefleri olarak kabul edilir. Geçmişte yapılan çalışmalarda bazı antidepresanların çeşitli mekanizmalar yoluyla antikanser etki gösterdiği bulunmuş ve bu nedenle antidepresanların antikanser ilaç olarak tekrar kullanılması araştırmacıların ilgisini çekmiştir. Bu çalışmada bazı antidepresanların (neferin (1), amoksapin (2), mirtazapin (3), agomelatin (4), trazodon hidroklorür (5), amitrptilin hidroklorür (6)) sitozolik hormon üzerindeki inhibisyon etkisinin araştırılması amaçlanmıştır. Sıçan karaciğeri TrxR aktivitesi üzerine bu moleküllerin inhibisyon etkileri IC50 ve Ki değerleri ile belirlendi. 1 (IC50:220 µM, Ki: 1,3±0,79 µM), 2 (IC50:337 µM, Ki: 5,2±2,1 µM), 3 (IC50:487 µM, Ki: 5,6±1,99 µM) ve 4 (IC50: 545) uM, Ki: 7,0±1,83 uM), sitozolik sıçan karaciğeri TrxR üzerinde güçlü inhibisyon etkisi sergiledi. Sonuç olarak, bu sonuçların hem bu antidepresanların antikanser mekanizmasını açıklamaya hem de antikanser etkileri olan yeni TrxR inhibitörlerinin sentezlenmesine katkı sağlayacağı düşünülmektedir.

Anahtar Kelimeler

• Antidepresan
• kanser
• tioredoksin redüktaz.

Evaluation of Some Antidepressants as Inhibitors of Thioredoxin Reductase Enzyme, which is an Anticancer Target

Öz

Thioredoxin reductase (TrxR) is an enzyme that is involved in many metabolic pathways from detoxification to reduction of radicals by catalyzing the reduction of thioredoxin, and is therefore associated with many physiological processes, including cancer. Inhibitors of this enzyme are considered anticancer targets. In past studies, some antidepressants have been found to have anticancer effects through various mechanisms, and therefore the reuse of antidepressants as anticancer drugs has attracted the attention of researchers. In this study, it was aimed to investigate the inhibition effect of some antidepressants (neferine (1), amoxapine (2), mirtazapine (3), agomelatine (4), trazodone hydrochloride (5), amitrptyline hydrochloride (6)) on cytosolic rat liver TrxR activity. The inhibition effects of these molecules were determined by IC50 and Ki values. 1 (IC50:220 µM, Ki: 1.3±0.79 µM), 2 (IC50:337 µM, Ki: 5.2±2.1 µM), 3 (IC50:487 µM, Ki: 5.6±1.99 µM) and 4 (IC50: 545 µM, Ki: 7.0±1.83 µM) exhibited potent inhibition effect on cytosolic rat liver TrxR. As a result, it was hoped that these results might contribute to both explaining the anticancer mechanism of these antidepressants and synthesizing new TrxR inhibitors with anticancer effects

Anahtar Kelimeler

• Antidepressant
• cancer
• thioredoxin reductase

Kaynakça

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