Current Perspectives on Pyrroloiminoquinones: Distribution, Biosynthesis and Drug Discovery Potential

Abstract

Pyrroloiminoquinones are a group of cytotoxic alkaloids most commonly isolated from marine sponges. Structurally, they are based on a tricyclic pyrrolo[4,3,2-de]quinoline core and encompass marine natural products such as makaluvamines, tsitsikammamines and discorhabdins. These diverse compounds are known to exhibit a broad spectrum of biological activities including anticancer, antiplasmodial, antimicrobial, antifungal and antiviral activities as well as the inhibition of several key cellular enzymes. The resurgence of interest in pyrroloiminoquinones and the convoluted understanding regarding their biological activities have prompted this review. Herein, we provided a concise summary of key findings and recent developments pertaining to their structural diversity, distribution, biogenesis, and their potential as chemical probes for drug development, including a discussion of promising synthetic analogs.

Structural Insights into the Marine Alkaloid Discorhabdin G as a Scaffold towards New Acetylcholinesterase Inhibitors

“…Notably, in recent years, dimers [9,10] and trimers [10] have also been reported to have often displayed good cytotoxicity. However, it is also known that, despite the potent in vitro activity obtained for selected discorhabdin alkaloids (e.g., discorhabdin A) against some human tumor cell lines, they were ineffective in model mouse studies [11].…”

Formation of Trideuteromethylated Artifacts of Pyrrole-Containing Natural Products

“…The pyrroloiminoquinones are cytotoxic alkaloids most commonly isolated from marine sponges, hydroids, cultured myxomycetes, and the fruiting bodies of terrestrial fungi . Structurally, they are based on a tricyclic pyrrolo­[4,3,2- de ]­quinoline core common to marine natural products such as makaluvamines (and related compounds damirones, batzellines, and macrophilones), bispyrroloiminoquinones (tsitsikammamines, zyzzyanones, and wakayins), and the discorhabdins (and related compounds prianosins and epinardins). , Over 110 members of the pyrroloiminoquinone class have been reported to date, and more than 50 of those are discorhabdins . The basic discorhabdin skeleton features a pyrido­[2,3- h ]­pyrrolo­[4,3,2- de ]­quinoline core with various substitutions of the pyrrole, pyridine, and spiro-dienone rings.…”

“…This class of compounds has attracted increasing interest of the scientific community due to its broad spectrum of biological activities including anticancer, antiplasmodial, antimicrobial, antifungal, and antiviral activity, as well as inhibitory activity against several classes of enzymes . Recently, (−)-discorhabdin L was found to have antitumor activity in LNCaP prostate cancer cell line mouse xenografts, and our work was focused on the isolation of discorhabdin L in sufficient quantities to support in vivo experiments.…”

Silver‐Catalyzed Tandem Reaction of β‐Alkynyl Ketones toward Spiro[isochromene‐1,4′‐quinoline] with Anticancer Activities

“…Among these skeletons, the spiro-4quinolones comprise a core structure of such alkaloids as sespenine, aspernomine, lanceomigine, mersinine, epinardin, and so on (Figure 1). [3] These structures have demonstrated antitumor, antibacterial, antimicrobial, and other important pharmacological activities. [3][4] To its significance, a few synthetic methods for such spiro-4-quinolones have been provided, [5] but most cases needed functionalized starting materials, with limited substrate scope and low selectivity.…”

“…[3] These structures have demonstrated antitumor, antibacterial, antimicrobial, and other important pharmacological activities. [3][4] To its significance, a few synthetic methods for such spiro-4-quinolones have been provided, [5] but most cases needed functionalized starting materials, with limited substrate scope and low selectivity. In this context, the development of novel and practical pathways for the atom-economical synthesis of spiro-4quinolones, and especially the corresponding bioactivity assays for such spiro structure, is of utmost interest.…”