PO-413 Estimation of antitumor activity of amino derivatives of quinoxaline-2-carbonitrile 1,4-dioxide

Abstract

IntroductionCancer is one of the well-known illnesses leading to death. Clinical validations prove that protein kinases are an attractive class of therapeutic drug targets for cancer as demonstrated with the recent approval of six protein kinase inhibitors. The Warburg effect describes the particular reliance of cancer cells on glycolysis for energy. Increased glycolysis and acid resistance have been postulated to be an essential part of carcinogenesis, conferring a significant growth advantage as well as promoting typical tumour progression. Targeting accelerated glycolysis in cancer cells is a new promising modality for treatment of cancer. Inhibition of glycolysis can be done without significant side effects, and such treatment will be additive to most known cancer therapies.One way to inhibit the metabolism of cancer cells is to inhibit Hexokinase 2 (HK-2) enzyme. HK-2 has been studied in the field of cancer metabolism and hopeful results obtained. It has been also confirmed that HK-2 enzyme is expressed 10–15 times more in cancer cells than normal cells. Inhibition of HK-2 enzyme will prevent cancer cells from nutrition and and it is expected that speeding of cancer cells will presumably stop tumour growth.Material and methodsRecent studies show that Methyl Jasmonate reveals promising results for treatment of cancer as a HK-2 inhibitor. Cis-jasmone, Jasmonic acid and Methyl jasmonate are cyclopentanones that are fatty acid derivatives. Jasmonates are plant stress hormones which exhibit abnormal anti-cancer activity.1 Jasmonates induced suppression of cell proliferation and death in a variety of cancer cell lines and cytotoxicity to cervical cancer cells with almost no effect on normal primary human keratinocytes.2 As a result of our research, although methyl jasmonate is long-known natural product, it has not well-studied as an anti cancer agent.Results and discussionsIn our research laboratory, we designed and synthesised handfull of novel methyl jasmonate analogues. We will highlight the biological activity results of those novel analogues as anti-cancer agents as well as their toxicologic profiles will be highligted.ConclusionAs a result of this study, we have identified several novel methyl jasmonate analogues that are much more potent in biological assays. Based on the synthetic feasibility and freedom of operation of methyl jasmonate molecule, additional druggable analogues are also being investigated in our research.This project (215 S890) is funded by TUBITAK. We kindly appreciate for their support.