indole-3-acetonitrile and indole-3-carbaldehyde

In our continuing work on synthesizing 4-substituted indole alkaloids as simple as possible by creating suitable reactions, we developed synthetic methods for 4-substituted indoles having a nitrogen or oxygen functional group at the 4-position starting from indole-3-carbaldehyde and one step conversion method of indole-3-carbaldehydes into indole-3-acetonitriles. Utilizing them, we could establish a practical synthetic route to 1,3,4,5-tetrahydropyrrolo[4,3,2-de]-quinoline in three steps from indole-3-carbaldehyde. On the basis of these results, short step total syntheses of marine indole alkaloids, such as isobatzelline C, batzelline C, makaluvamine A, and damirones A and B, were achieved. Furthermore, a novel preparative method of psilocin was established in only five steps from indole-3-carbaldehyde. The syntheses of psilocin analogs having a formyl group or bromine in the benzene part were also achieved.

Topics: Alkaloids; Chemistry, Organic; Indoles

Influenza A viruses are serious zoonotic pathogens that continuously cause pandemics in several animal hosts, including birds, pigs, and humans. Indole derivatives containing an indole core framework have been extensively studied and developed to prevent and/or treat viral infection. This study evaluated the anti-influenza activity of several indole derivatives, including 3-indoleacetonitrile, indole-3-carboxaldehyde, 3-carboxyindole, and gramine, in A549 and MDCK cells. Among these compounds, 3-indoleacetonitrile exerts profound antiviral activity against a broad spectrum of influenza A viruses, as tested in A549 cells. Importantly, in a mouse model, 3-indoleacetonitrile with a non-toxic concentration of 20 mg/kg effectively reduced the mortality and weight loss, diminished lung virus titers, and alleviated lung lesions of mice lethally challenged with A/duck/Hubei/WH18/2015 H5N6 and A/Puerto Rico/8/1934 H1N1 influenza A viruses. The antiviral properties enable the potential use of 3-indoleacetonitrile for the treatment of IAV infection.

Topics: A549 Cells; Animals; Antiviral Agents; Dogs; Female; Humans; Indoles; Influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Lung; Madin Darby Canine Kidney Cells; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Orthomyxoviridae Infections; Sulfides; Viral Load; Virus Replication

The metabolism of the cruciferous phytoalexins brassinin and cyclobrassinin, and the related compounds indole-3-carboxaldehyde, glucobrassicin, and indole-3-acetaldoxime was investigated in various plant tissues of Brassica juncea and B. rapa. Metabolic studies with brassinin showed that stems of B. juncea metabolized radiolabeled brassinin to indole-3-acetic acid, via indole-3-carboxaldehyde, a detoxification pathway similar to that followed by the "blackleg" fungus (Phoma lingam/Leptosphaeria maculans). In addition, it was established that tetradeuterated brassinin was incorporated into the phytoalexin brassilexin in B. juncea and B. rapa. On the other hand, the tetradeuterated indole glucosinolate glucobrassicin was not incorporated into brassinin, although the chemical structures of brassinins and indole glucosinolates suggest an interconnected biogenesis. Importantly, tetradeuterated indole-3-acetaldoxime was an efficient precursor of phytoalexins brassinin, brassilexin, and spirobrassinin. Elicitation experiments in tissues of Brassica juncea and B. rapa showed that indole-3-acetonitrile was an inducible metabolite produced in leaves and stems of B. juncea but not in B. rapa. Indole-3-acetonitrile displayed antifungal activity similar to that of brassilexin, was metabolized by the blackleg fungus at slower rates than brassinin, cyclobrassinin, or brassilexin, and appeared to be involved in defense responses of B. juncea.

Topics: Anti-Infective Agents; Brassicaceae; Cells, Cultured; Glucosinolates; Indoles; Isotope Labeling; Phytoalexins; Plant Extracts; Plant Leaves; Plant Roots; Plant Stems; Sesquiterpenes; Terpenes; Thiocarbamates

Dietary indoles in cruciferous vegetables induce cytochrome P450 enzymes and have prevented tumors in various animal models. Because estradiol metabolism is also cytochrome P450 mediated and linked to breast cancer risk, indoles may similarly reduce estrogen-responsive tumors in humans. We examined several indoles in female Sprague-Dawley rats for induction of hepatic estradiol 2-hydroxylation. The most potent inducer, indole-3-carbinol, was administered to humans (500 mg daily for 1 wk). It significantly increased the extent (mean +/- SEM) of estradiol 2-hydroxylation from 29.3% +/- 2.1% to 45.6% +/- 2.1% (P less than .001). These results indicate that indole-3-carbinol strongly influences estradiol metabolism in humans and may provide a new chemopreventive approach to estrogen-dependent diseases.

Topics: Animals; Carboxylic Acids; Cytochrome P-450 Enzyme System; Diet; Estradiol; Humans; Hydroxylation; Indoles; Male; Mice; Mice, Inbred Strains