Pyrrole as an Important Scaffold of Anticancer Drugs: Recent Advances

Abstract

With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents need to be taken. Pyrrole moiety has been found in various active compounds with anti-inflammatory, antiseptic, antibacterial, lipid-lowering and anticancer properties. Recent advances in the exploration of highly active and selective cytotoxic structures containing pyrrole motifs have shown promising data for future investigations. Accordingly, this review presents an overview of recent developments in the pyrrole derivatives as anticancer agents, with a main focus towards the key moieties required for the anti-tumor activities. Pyrrole molecules comprising prominent targeting capacities against microtubule polymerization, tyrosine kinases, cytochrome p450 family 1, histone deacetylase and bcl-2 proteins were reported. In addition, several mechanisms of action, such as apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others were analyzed. Furthermore, in most of the discussed cases we provided synthesis schemes of the mentioned molecules. Overall, the utilization of pyrrole scaffold for the design and synthesis of novel anticancer drugs could be a promising approach for future investigations.

DeepAR: a novel deep learning-based hybrid framework for the interpretable prediction of androgen receptor antagonists

“…S4). Interestingly, the pyrrole moiety is present in various active compounds exhibiting anticancer, antibacterial, anti-inflammatory and anti-hypertensive properties [ 72 ]. Numerous research into the potential of pyrrole and its derivatives as a highly active scaffold has previously been explored [ 73 – 75 ].…”

Novel pyrrolopyrimidine derivatives: design, synthesis, molecular docking, molecular simulations and biological evaluations as antioxidant and anti-inflammatory agents

“…Many pathways have been reported for the LPS-macrophages activated by the TLR4 agonist and/or induced by TLR2/MyD88 activation, which is important for inflammatory processes are characterised by increased COX-2 accounting for the bulk of PGE biosynthesis 93 , 107 . NSAIDs inhibit both COXs enzymes and decrease production of PGE2 among these pyrrole containing compounds 108–110 . These compounds block PGE synthesis by non selective inhibition (indomethacin, acemetacin, tolmetin and ketorolac) or by selective-inhibition of COX-2 (etodolac).…”

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities

“…Pyrroles possess a flat and electron-rich aromatic ring, and their structure is susceptible to electrophilic attack and can also interact with a variety of biomolecules via hydrogen bonds as well as π–π stacking interactions [ 19 ]. Because of their intriguing structures and wide range of biomedical properties, various pyrrole-based compounds have been studied for pharmacological activities [ 16 , 20 , 21 , 22 ]. Streptopyrroles are one of the examples of pyrrole-containing compounds with potent antimicrobial properties and inhibitory activity on the nitrogen regulator II (NRII) histidine kinase from Escherichia coli [ 23 ].…”