Indole-Based Small Molecules as Potential Therapeutic Agents for the Treatment of Fibrosis

Abstract

Indole alkaloids are widely distributed in nature and have been particularly studied because of their diverse biological activities, such as anti-inflammatory, anti-tumor, anti-bacterial, and anti-oxidant activities. Many kinds of indole alkaloids have been applied to clinical practice, proving that indole alkaloids are beneficial scaffolds and occupy a crucial position in the development of novel agents. Fibrosis is an end-stage pathological condition of most chronic inflammatory diseases and is characterized by excessive deposition of fibrous connective tissue components, ultimately resulting in organ dysfunction and even failure with significant morbidity and mortality. Indole alkaloids and indole derivatives can alleviate pulmonary, myocardial, renal, liver, and islet fibrosis through the suppression of inflammatory response, oxidative stress, TGF-β/Smad pathway, and other signaling pathways. Natural indole alkaloids, such as isorhynchophylline, evodiamine, conophylline, indirubin, rutaecarpine, yohimbine, and vincristine, are reportedly effective in organ fibrosis treatment. In brief, indole alkaloids with a wide range of pharmacological bioactivities are important candidate drugs for organ fibrosis treatment. The present review discusses the potential of natural indole alkaloids, semi-synthetic indole alkaloids, synthetic indole derivatives, and indole-contained metabolites in organ fibrosis treatment.

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

“…Indole alkaloids are currently a hotspot of research for pharmacologists due to their high market share and multiple physiological activities. These compounds have a broad range of biological activities, such as anxiolytic, anticonvulsant, antiviral, anti-inflammatory, anti-fibrosis, antiparasitic, antibacterial, anti-arrhythmic, and antitumor properties [ 10 , 24 , 25 ]. Particularly, most of them are isolated from marine organisms such as fungi, bacteria, mollusks, sponges, and algae.…”

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

“…In an article, the total releasing duration of pirfenidone is prolonged by using acellular peritoneal matrix-loaded pirfenidone nanodroplets, which alleviates cardiac fibrosis ( Fu et al, 2022b ). Except pirfenidone, there are several interventions targeting TGF-β signaling pathway against cardiac fibrosis, such as dihydrolycorine, choline, indole alkaloids, and indole derivatives ( Qin et al, 2022 ). Moreover, 2,5-dimethylcelecoxib inhibits the TGF-β axis and suppresses CF-to-MF transformation in a cryoinjury-induced MI model ( Ikushima et al, 2022 ).…”

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential

“…Cyanoenone is an extended fragment of enone, in which cyano and carbonyl groups have the potential to interact with DNA or enzymes through hydrogen bonds, exists in various drugs, such as entacapone, teriflunomide ( Figure 1 ), and bardoxolone, exhibiting a broad range of pharmacological activities. Indole is a fused nitrogen-containing heterocycle, which can be used as a signal molecule to modulate multiple biological processes, including bacterial pathogenesis [ 23 , 24 , 25 ], and has been presented in many important pharmaceuticals, such as indolmycin, daptomycin, and indomethacin, displaying good pharmacokinetic properties [ 26 , 27 , 28 ]. Hence, introducing indolylcyanoenone composed of indole and cyanoenone into the coumarin scaffold might be an effective strategy to construct a new antibacterial framework against drug-resistant bacteria.…”