Indole-Containing Natural Products 2019–2022: Isolations, Reappraisals, Syntheses, and Biological Activities

Abstract

Indole alkaloids represent a large subset of natural products, with more than 4100 known compounds. The majority of these alkaloids are biologically active, with some exhibiting excellent antitumor, antibacterial, antiviral, antifungal, and antiplasmodial activities. Consequently, the natural products of this class have attracted considerable attention as potential leads for novel therapeutics and are routinely isolated, characterized, and profiled to gauge their biological potential. However, data on indole alkaloids, their various structures, and bioactivities are complex due to their diverse sources, such as plants, fungi, bacteria, sponges, tunicates, and bryozoans; thus, isolation methods produce an incredible trove of information. The situation is exacerbated when synthetic derivatives, as well as their structures, bioactivities, and synthetic schemes, are considered. Thus, to make such data comprehensive and inform researchers about the current field’s state, this review summarizes recent reports on novel indole alkaloids. It deals with the isolation and characterization of 250 novel indole alkaloids, a reappraisal of previously reported compounds, and total syntheses of indole alkaloids. In addition, several syntheses and semi-syntheses of indole-containing derivatives and their bioactivities are reported between January 2019 and July 2022.

One-Pot Synthesis of Polynuclear Indole Derivatives by Friedel–Crafts Alkylation of γ-Hydroxybutyrolactams

“…A vast pool of indole derivatives, both naturally occurring [ 1 ] and synthetic [ 2 ], have long been a valuable source of potential leads for novel therapeutics, as the majority of indoles are biologically active exhibiting, among others, antitumor [ 3 ], anti-Alzheimer’s [ 4 ], antiviral [ 5 ], antituberculosis [ 6 ], antimalarial [ 7 ] and antibacterial [ 8 ] properties. In this context, a subclass of polynuclear indoles, such as cryptolepine [ 9 ], isocryptolepine 1 [ 10 , 11 ] and neocryptolepine [ 12 ] alkaloids or paullone 2 derivatives [ 13 ], stand somewhat alone, because their preparation usually involves time-consuming, multi-step synthetic procedures ( Figure 1 ).…”

Gene-Directed Generation of Unprecedented Bioactive Compounds

“…Conversion Experiments. The equimolar mixtures of I3C with each of DPHBO (2), DHMCO (4), and DPBO (7) were added to test tubes preloaded with the fungal intracellular/extracellular protein in ME medium or phosphate buffer (pH = 7). After being agitated for 2 h at 28 °C, the reactant mixtures were extracted with EtOAc and evaporated under vacuum to yield residues that were dissolved in 200 μL of methanol for LC-HRMS analysis.…”

“…17,22 ■ RESULTS AND DISCUSSION Effect of I3C on ChrA and ChrB Expressions. The expression of ChrA and ChrB was found to be critical for the architectural construction of the chromane-based pentaketides, including DPB (1), DHMCO (4), PBEO (6), and DPBO (7). 19 Accordingly, this study started by investigating the effect of I3C on the expression of ChrA and ChrB genes in fungi.…”

“…Indeed, the intrinsic reactivity of indole has endowed it with a “privileged structure” in drug discovery . However, the complexity of their molecular architecture and the presence of reactive functional groups pose tremendous challenges to the chemical synthesis of polyketides and indole alkaloids, as well as their hybrids, , thus hampering our ability to discover new valuable molecular scaffolds. , Relatively clearer is that many polyketide synthases (PKSs) of I to III types use a broad range of biosynthetic building blocks to construct various molecular frameworks. , However, the biosynthesis of natural indole alkaloids is more complex. , It is even more difficult to construct polyketide–indole hybrids (PIHs) with unprecedented molecular frameworks.…”

Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives

“…Despite these recent achievements, to the best of our knowledge, neither sclareolide-indole conjugate nor sclareolide-polyphenol conjugate has been reported, as shown in Figure 1 . In view of the interesting biological activities of sclareolide and its derivatives, we aimed to synthesize novel sclareolide derivatives containing various indoles or polyphenol methyl ethers, given their high prevalence in bioactive compounds and drugs [ 19 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. As part of our ongoing interest [ 29 ] in finding natural product derivatives with potent antitumor activities, we herein report our synthesis and the biological evaluation of a new series of sclareolide-indole conjugates and their derivatives.…”