1,3-Dipolar Cycloaddition of Nitrile Oxides and Nitrilimines to (-)-β-Caryophyllene: Stereoselective Synthesis of Polycyclic Derivatives and Their Biological Testing.

The cycloaddition of nitrile oxides and nitrilimines to one or both of the C=C double bonds of caryophyllene is described. The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrilimines to caryophyllene was demonstrated. As a result of these reactions, pharmacophore fragments of isoxazoline and pyrazoline are introduced into the structure of caryophyllene, which leads to an increase in the conformational rigidity of the molecule.

Smart nanocarriers for enzyme-activated prodrug therapy.

Exogenous enzyme-activated prodrug therapy (EPT) is a potential cancer treatment strategy that delivers non-human enzymes into or on the surface of the cell and subsequently converts a non-toxic prodrug into an active cytotoxic substance at a specific location and time. The development of several pharmacological pairs based on EPT has been the focus of anticancer research for more than three decades. Numerous of these pharmacological pairs have progressed to clinical trials, and a few have achieved application in specific cancer therapies.

The potential of methioninase for cancer treatment.

Cancer cells are addicted to L-methionine (L-Met) and have a much greater requirement for L-Met than normal cells due to excess transmethylation, termed the Hoffman effect. By targeting this vulnerability through dietary restriction of L-Met, researchers have been able to achieve promising results in inhibiting tumor growth and eradicating cancer cells. Methioninase (EC 4.

Targeting Methionine Addiction of Cancer Cells with Methioninase.

All types of cancer cells are addicted to methionine, which is known as the Hoffman effect. Restricting methionine inhibits the growth and proliferation of all tested types of cancer cells, leaving normal cells unaffected. Targeting methionine addiction with methioninase (METase), either alone or in combination with common cancer chemotherapy drugs, has been shown as an effective and safe therapy in various types of cancer cells and animal cancer models.

Predictive markers for efficiency of the amino-acid deprivation therapies in cancer.

Amino acid deprivation therapy (AADT) is a promising strategy for developing novel anticancer treatments, based on variations in metabolism of healthy and malignant cells. L-asparaginase was the first amino acid-degrading enzyme that received FDA approval for the treatment of acute lymphoblastic leukemia (ALL). Arginase and arginine deiminase were effective in clinical trials for the treatment of metastatic melanomas and hepatocellular carcinomas.

Methionine γ-Lyase-Daidzein in Combination with S-Propyl-L-cysteine Sulfoxide as a Targeted Prodrug Enzyme System for Malignant Solid Tumor Xenografts.

The purpose of this study was to determine the anticancer effect of dipropyl thiosulfinate produced in situ by the pharmacological pair: (1) conjugated with daidzein C115H methionine γ-lyase (EC 4.4.1.