7-8-dimethylalloxazine and isoalloxazine

Two novel compounds bearing heterocyclic nitrogen, 2-pyridone alkaloid (1) and alloxazine derivative (2), along with the known pretenellin B (3), pyridovericin (4) and lumichrome (5) were isolated from a culture of the entomopathogenic fungal strain Beauveria bassiana. The chemical structures of 2-pyridone alkaloid and alloxazine derivative were established on the basis of the interpretation of spectroscopic data. The isolated compounds were evaluated in a panel of five cancer cell lines and pyridovericin exhibited cytotoxicity (IC

Topics: Alkaloids; Antineoplastic Agents; Beauveria; Cell Line, Tumor; Drug Screening Assays, Antitumor; Flavins; Humans; Molecular Structure; Monosaccharides; Pyridones; Secondary Metabolism

In this work we have studied the photophysics of biologically active flavin molecule lumichrome (LCM) in different bile-salt aggregates. With alteration of the functional groups of the bile salts, the photophysics of confined fluorophore is largely affected and shows difference in their spectral behavior. This study also reveals the selective prototropic species of LCM present in bile salt aggregates. In the presence of the bile salt aggregates, LCM molecule shows excitation and emission wavelength-dependent emission properties, indicating switch over of the structural change of different prototropic form of the LCM molecule. The observation of higher rotational relaxation time in NaDC aggregates compared to NaTC aggregates clearly reflects that NaDC aggregates are more rigid due to its greater hydrophobicity and large in size, which is capable to bind the guest molecule more into their nanoconfined medium. Moreover, due to less acidic nature, NaDC aggregates have more ability to accept hydrogen bond from the LCM molecule and show the selective formation of isoalloxazine N10 anion (A1 monoanionic form) of LCM.

Topics: Bile Acids and Salts; Flavins; Hydrogen Bonding; Molecular Conformation

Effects of the coenzyme flavin mononucleotide (FMN) and its analogs on the self-splicing of primary transcripts of the phage T4 thymidylate synthase gene (td) have been investigated. Among all flavins and analogs tested, the lumichrome was the most inhibitory. The kinetic analysis demonstrated that FMN acts as a competitive inhibitor for the td intron RNA with a Ki of 1.86 mM although it does not possess a guanidino group in its structure. FMN is able to inhibit the first step of the self-splicing, thus identifying FMN as a novel class of group I intron splicing inhibitors. The specificity of the splicing inhibition by FMN is predominantly due to changes in Km but not k(cat). The splicing inhibition is believed to be due to the interference with the affinity of GTP for the intron RNA. The analysis of the inhibitory concentration and structural examination suggests that the key structural features in FMN responsible for the inhibition of splicing may be an alloxazine group.

Topics: Bacteriophage T4; Dose-Response Relationship, Drug; Flavin Mononucleotide; Flavins; Guanosine Triphosphate; Interferon alpha-2; Interferon-alpha; Kinetics; Pteridines; Recombinant Proteins; RNA Splicing; Thymidylate Synthase