The evaluation of anticancer and antiinflammatory effects of methylthiazole derivatives

Inflammatory responses play a decisive role in different stages of cancer development including malignant transformation, invasion and metastasis. Today, the preferred anti-inflammatory and anticancer drugs are very limited due to their high toxicity, low efficacy and drug resistance. Therefore, anti-inflammatory and anticancer drug design studies with less toxic and highly effective mechanisms have gained importance. Thiazole-derived compounds are very important in the design of new drugs because they are present in the structure of important biologically active compounds used in the treatment of cancer. In this thesis, the inhibitory effect potential of newly synthesized 4-Methylthiazole derivative compounds on cyclooxygenase (COX) and lipoxygenase (LOX) enzymes were investigated. Furthermore, cytotoxicity values of these synthesized compounds on A549, C6 and NIH/3T3 cell lines were determined by MTT method and anticancer activities of the compounds were evaluated in A549 and C6 cell lines. When the early/late apoptotic and necrotic cell ratio measured by annexin V-FITC method, mitochondrial membrane integrity and caspase-3 activation levels measured by flow cytometry were evaluated, activation of BHD3-coded compound on both C6 and A549 cell line was observed to be higher than positive control cisplatin. BHD3 has also been shown to inhibit COX-1, COX-2 and LOX enzyme activity. The findings obtained from our study show that BHD3 coded compounds have the potential of antiinflammatory and anticancer effects and will contribute to drug development studies based on thiazole derivative compounds. Keywords: 4-Methylthiazole derivatives, Antiinflammation, Anticancer, Lipoxygenase, Cyclooxygenase.