Relationships of Prodiginins Mechanisms and Molecular Structures to their Antiproliferative Effects

Oct 21, 2026

Uploaded by Hazel

The review examines prodiginins (PGs) natural pigments, bacterial secondary metabolites produced by gram-negative and gram-positive species, with emphasis on Serratia and Streptomyces. It describes their shared tripyrrolic core alongside variable side chains and cyclization that generate structural diversity. The article synthesizes evidence on PG-induced apoptosis and highlights structure-activity relationships across cancer cell lines. It further discusses how certain PGs have progressed toward clinical trials, supporting future anticancer drug development and targeted therapies based on PGs or derivatives.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Keywords

1. INTRODUCTION

Natural products as anticancer inspirations

Prodiginins family, structure, and sources

Biosynthesis of prodigiosin and undecylprodigiosin

Genetic clusters and biosynthetic regulation

Mechanisms of action in cancer cells

Send Orders for Reprints [to reprints@benthamscience.net](to reprints@benthamscience.net) Anti-Cancer Agents in Medicinal Chemistry, XXXX, XX, 0-0 1 MINI-REVIEW ARTICLE Relationships of Prodiginins Mechanisms and Molecular Structures to their Antiproliferative Effects El Abbassi Ayoub 1,*, Zineb Azoubi 1, Zougagh Nadia 1, Mouslim Assia 1 and Menggad Mohammed 1 1Laboratory of Physiopathology and Molecular Genetics, Department of Biology, Faculty of Sciences Ben M’Sik, Hassan II University, Casablanca, Morocco Abstract: The Prodiginins (PGs) natural pigments are secondary metabolites produced by a broad spectrum of gram-negative and gram-positive bacteria, notably by species within the Serratia and Streptomyces genera. These compounds exhibit diverse and potent biological activities, including anticancer, immunosuppressive, antimicro A R T I C L E H I S T O R Y bial, antimalarial, and antiviral effects. Structurally, PGs share a common tripyrrolic core but possess variable Received: March 25, 2024 side chains and undergo cyclization, resulting in structural diversity. Studies have investigated their antiprolifera RevAccsept:dJ:uneJuly2512,,20220424 tive effects on various cancer cell lines, with some PGs advancing to clinical trials for cancer treatment. This review aims to illuminate the molecular mechanisms underlying PG-induced apoptosis in cancer cells and explore D10OI:2174/0118715206314212240805105735 the structure-activity relationships pertinent to their anticancer properties. Such insights may serve as a foundation for further research in anticancer drug development, potentially leading to the creation of novel, targeted therapies based on PGs or their derivatives. Keywords: Antiproliferative, bacterial pigments, Bcl-2, BH3 mimetics, PGs. 1. INTRODUCTION Natural compounds originating from plants and bacteria have been, and continue to be, the primary source of inspiration for anticancer drug design [1-5] . Especially, bacterial strains have been the source of effective chemotherapeutic agents used in cancer treatment, such as doxorubicin, bleomycin, and dactinomycin [5-10] . Despite this, the heterogeneous and diverse molecular causes of cancer, coupled with the developed chemoresistance against traditional drugs, encourage the continuous search for new, similar compounds [11] . One of these promising molecules is Prodiginins (PGs), bioactive secondary metabolites. The PGs family are of atripyrrolic chemical nature and produced by different gram-positive bacteria such as actinomycetes species of the genus Streptomycesand gram-negative bacteria of the genus Serratia [1] . The PGs have shown antimalarial [12], antibiotic [13], immunosuppressive [14], and antiproliferative activities against different cancer cell lines (human and non-human) [15-17], among other biological activities. PG analogs exhibit significant structural variation across different bacterial strains, and some species are known to produce multiple PG analogs concurrently within a single bacterial cell [18, 19] . The PGs of actinomycete strains such as Streptomyces coelicolor include undecylprodigiosin and some of its cyclic analogs: butylmeta-cyclo-heptyl-prodigiosin, ethyl-meta-cyclo-nonyl-prodigiosin, and methyl-cyclo-decyl-prodigiosin [20] . The most described PG is called prodigiosin, a red pigment biosynthesized by species of the genus Serratia, like Serratia marcescens, and other species, such as Hahella chejuensis and Pseudomonas magnesiorubra [1, 19](Fig. 1) . The biosynthesis of prodigiosin and undecylprodigiosin has involved the condensation of two metabolic pathway products. The first pathway, which is common in all PGs-producing species, produces bi-pyrroles named MBC (4-methoxy-2,2′-bipyrrole-5-carbaldehyde) or HBC (4-hydroxy-2,2’-bipyrrole-5-carbaldehyde) . *Address correspondence to this author at the Laboratory of Physiopathology and Molecular Genetics, Department of Biology, Faculty of Sciences Ben M’Si

FAQs

What biological activities do prodiginins (PGs) exhibit beyond anticancer effects?

PGs display a range of potent activities including immunosuppressive, antimicrobial, antimalarial, and antiviral effects, alongside antiproliferative effects against cancer cell lines.

What structural feature do prodiginins share, and what creates their diversity?

PGs share a common tripyrrolic core, while diversity arises from variable side chains, cyclization, and differences in chemical moieties across producing strains.

Which pathways are involved in producing prodiginins, and how do they contribute to tripyrrolic molecules?

Biosynthesis involves condensation of metabolic pathway products: one pathway yields bi-pyrroles (MBC or HBC) and the second yields mono-pyrroles (MAP and 2-UP), whose condensation forms PGs’ tripyrrolic structures (cycles A, B, and C).

Oct 21, 2026

Uploaded by Hazel