In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species in an iron-dependent manner.
Effective management of advanced cancer requires systemic treatment including small molecules that target unique features of aggressive tumor cells. At the same time, tumors are heterogeneous and current evidence suggests that a subpopulation of tumor cells, called tumor initiating or cancer stem cells, are responsible for metastatic dissemination, tumor relapse and possibly drug resistance. Classical apoptotic drugs are less effective against this critical subpopulation. In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen
The purpose of this study is to underline the progression and development of research regarding oxygen-containing heterocycles as well as the contribution that some oxygen-containing heterocycles have made as anticancer medicines. A series of publications about the antitumor effects of derivatives of heterocyclic compounds containing an oxygen atom, such as furan, benzofuran, oxazole, benzoxazole, and oxadiazole, were evaluated, and their anticancer activities showed encouraging results when compared to those of established standard treatments.
The application of physiological oxygen (physoxia) concentrations is becoming increasingly commonplace within a mammalian stem cell culture. Human mesenchymal stem cells (hMSCs) attract widespread interest for clinical application due to their unique immunomodulatory, multi-lineage potential, and regenerative capacities. Descriptions of the impact of physoxia on global DNA methylation patterns in hMSCs and the activity of enzymatic machinery responsible for its regulation remain limited. Human bone marrow-derived mesenchymal stem cells (BM-hMSCs, passage 1) isolated in reduced oxygen conditions displayed an upregulation of SOX2 in reduced oxygen conditions vs. air oxygen (21% O2, AO), while no change was noted for either OCT-4 or NA
... Show MoreAryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in Prevotella and Lactobacillus, while decreasing Sutterella and Bacteroides. Fecal transplants from TCDD-treated
... Show MoreThe pharmacophore 2-aminothiazole has an interesting role in pharmaceutical chemistry as this led to the synthesis of many types of compounds with diverse biological activity. Schiff base derivatives at the same time contribute to drug evolution importantly. In this review, the Schiff base derivatives of 2-aminothiazole formed and some of their metal complexes are being focused on, and the antimicrobial and anticancer activity of them is being illustrated.
The pharmacophore 2-aminothiazole has an interesting role in pharmaceutical chemistry as this led to the synthesis of many types of compounds with diverse biological activity. Schiff base derivatives at the same time contribute to drug evolution importantly. In this review, the Schiff base derivatives of 2-aminothiazole formed and some of their metal complexes are being focused on, and the antimicrobial and anticancer activity of them is being illustrated.