Promising Prodiginins Biological Activities

Abstract

Prodiginins are a large family of at least 34 pyrrolic compounds, including the well-studied red pigment prodigiosin. Prodiginins are produced by several microorganisms displaying broad biological activities, including antimicrobial, antiviral, antiparasitic, antiproliferative, and immunosuppressive activities. The present review aims to compile and analyze the main physicochemical and biological properties and mechanisms of action of prodiginins for microbial disease treatment, particularly SARS-CoV-2 disease and opportunistic infections related to COVID-19. The interaction of prodigiosin, as a model molecule, with cellular membranes, potential drug delivery devices, and toxicological studies, and in silico studies using molecular dynamics showed that the prodigiosin motif, which interacts with lipids, opens a new door for the potential therapeutic use of prodiginins.

Keywords: antiviral; biocide activities; drug delivery models; in silico studies; nanodevices; prodiginins; prodigiosin.

FIGURE 1

Structures of some prodiginins reported in the literature. (A) Prodigiosin; (B) undecylprodigision; (C) cylcoprodigiosin; (D) decylcycloprodigiosin; (E) streptorubine; (F) nonylprodigiosin.

FIGURE 2

Chemical equilibrium of prodigiosin isomers [41].

FIGURE 3

Chemical structure of macrocyclic prodiginins: roseophilin (A) and prodigiosin R2 (B).

FIGURE 4

Docking results (A) and molecular interactions (B) of PG against E1A viral protein respectively. The binding energy of the PG‐E1A protein complex was −4.1 (modified from [179]).

FIGURE 5

Superposition of the binding mode predicted by docking for PG (magenta) and violacein (green) at the 5γ binding site in protomer A. Both dyes were located preferentially in an environment defined by residues Phe338A, Tyr365A, Tyr369A, Ala372A, Ser373A, Phe374A, Asp405C, Glu406C, Arg408C, Gln409C, Thr415C, Gly416C, Lys417C (A). Docking pose prediction for PG (B) (A modified from [185]).

FIGURE 6

RMSD (Å) versus time plot for the MD simulation on the docking complex for PG at the 5γ binding site in protomer A (A). PG predicted pose by docking (violet) and after 50 ns of MD (orange) at the 5γ binding site in protomer A. Considering the pose resulting from MD (orange), the ligand shows π‐stacking interactions with Phe338A, Tyr365A, Phe392A, and Phe515A through two of its pyrrole groups (B).

FIGURE 7

The distances between ligand atoms and key binding site residues of the Spike protein are determined during MD simulation. The aromatic ring of Phe338A‐pyrrole A of PG (A). The aromatic ring of Tyr365A‐pyrrole C of PG (B). The aromatic ring of Phe392A‐pyrrole A of PG (C). The aromatic ring of Phe515A‐pyrrole A of PG (D).

FIGURE 8

π‐stacking interactions between the protein aromatic rings and the pyrrole rings of PG.