Clear Search sequence regions


  • bacteria (1)
  • female (1)
  • Hep (1)
  • humans (1)
  • isomers (2)
  • mice (2)
  • MYP1 (3)
  • parasites (1)
  • plasmodium falciparum (2)
  • plasmodium yoelii (2)
  • prodigiosin (2)
  • Sizes of these terms reflect their relevance to your search.

    Highly efficient and straightforward synthetic routes toward the first total synthesis of 2-(p-hydroxybenzyl)-prodigiosins (2-5), isoheptylprodigiosin (6), and geometric isomers of tambjamine MYP1 ((E/Z)-7) have been developed. The crucial steps involved in these synthetic routes are the construction of methoxy-bipyrrole-carboxaldehydes (MBCs) and a 20-membered macrocyclic core and a regioselective demethylation of MBC analogues. These new synthetic routes enabled us to generate several natural prodiginines 24-27 in larger quantity. All of the synthesized natural products exhibited potent asexual blood-stage antiplasmodial activity at low nanomolar concentrations against a panel of Plasmodium falciparum parasites, with a great therapeutic index. Notably, prodiginines 6 and 24-27 provided curative in vivo efficacy against erythrocytic Plasmodium yoelii at 25 mg/kg × 4 days via oral route in a murine model. No overt clinical toxicity or behavioral change was observed in any mice treated with prodiginines and tambjamines.

    Citation

    Papireddy Kancharla, Yuexin Li, Monish Yeluguri, Rozalia A Dodean, Kevin A Reynolds, Jane X Kelly. Total Synthesis and Antimalarial Activity of 2-(p-Hydroxybenzyl)-prodigiosins, Isoheptylprodigiosin, and Geometric Isomers of Tambjamine MYP1 Isolated from Marine Bacteria. Journal of medicinal chemistry. 2021 Jun 24;64(12):8739-8754

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 34111350

    View Full Text