We report the preparation and cytotoxicity of two new eugenol derivatives that contain 1,3,4-oxadiazole, as novel inhibitors of thymidylate synthase; these derivatives are shown to be promising chemotherapeutic agents.

Semisynthetic modifications of natural products have bestowed us with many anticancer drugs. In the present work, a natural product, eugenol, has been modified synthetically to generate new anticancer agents. The final compounds were structurally confirmed by NMR, IR, and mass techniques. From the cytotoxicity results, compound 17 bearing morpholine was found to be the most active cytotoxic agent with IC 50 1.71 (MCF-7), 1.84 (SKOV3), and 1.1 μM (PC-3) and a thymidylate synthase (TS) inhibitor with an IC 50 of 0.81 μM. Further cellular studies showed that compound 17 could induce apoptosis and arrest the cell cycle at the S phase in PC-3 carcinoma. The docking study strongly favors compound 17 to be a TS inhibitor as it displayed a similar interaction to 5-fluorouracil. The in silico pharmacokinetics and DFT computational studies support the results obtained from docking and biological evaluation and displayed favorable pharmacokinetic profile for a drug to be orally available. Compound 17 was found to be a promising TS inhibitor which could suppress DNA synthesis and consequently DNA damage in prostate cancer cells.

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The electrode material is an important aspect for the efficiency and costs in the microbial fuel cells (MFCs). Enhancing of current production and bacteria attachment to the electrode are essential goals for developing the performance of MFCs. In this study, the role of the structural iron present in clays in enhancing the electron transfer of Shewanella oneidensis MR-1 was investigated. Two types of clay containing different amounts of iron situated in the octahedral sites were used to modify ITO (indium tin oxide) electrodes, namely nontronite NAu-1, and montmorillonite (Wyoming) SWy-1. Synthetic montmorillonite SYn-1 which is iron-free clay was used for comparison. The interaction between the bacterial cells and the clays was studied by potential-step chronoamperometry, cyclic voltammetry, confocal microscopy, and scanning electron microscopy (SEM). The obtained results showed that the current densities generated upon ITO electrode modification using the NAu-1 and SWy-1 iron-containing clays were 19 and 3 times higher than that produced using the bare ITO electrode. No current density was obtained when utilizing the synthetic montmorillonite SYn-1 clay. SEM and confocal microscopy observations confirmed the increased coverage percentage of the bacterial cells attached to the clay-modified electrodes compared to the bare ITO.

The role of structural iron in clays to enhance the electron transfer of Shewanella Oneidensis MR-1 was investigated. Three types of clays containing different amounts of iron situated in the octahedral sites have been used to modify the ITO electrodes: nontronite NAu-1, montmorillonite (Wyoming) SWy-1, and synthetic montmorillonite SYn-1. The interaction between bacterial cells and the clay, which modified the ITO electrodes were studied by potential step, cyclic voltammetry, confocal microscope, and scanning electron microscope SEM. Experimental results showed that the current density generated using iron containing clays NAu-1 and SWy-1 to modify the ITO electrode was 19 and 3 times higher than that produced using the bare ITO electrode. Mechanism of electrochemical production deviated for the iron containing clay NAu-1 Keywords Shewanella Oneidensis MR-1, Clay, Modified ITO electrode, MFC