Racemic Bisindole Alkaloids: Structure, Bioactivity, and Computational Study

Abstract

Main observation and conclusion The new racemic and dimeric indole alkaloids with the characteristic cyclopenta[b]indole backbone, (+)‐ and (–)‐spondomine (1a/1b), were isolated from a cultured sponge Tedania anhelans. A semi‐synthesis was employed to obtain 1a/1b and the other four stereoisomers 1c—1f. Their structures were determined by spectroscopic analysis, single‐crystal X‐ray, and quantum chemical calculations. Six stereoisomers differ in bioactivity according to their absolute configurations. Especially, (+)‐spondomine (1a) displayed cytotoxicity against the K562 cell line and exhibited stronger Wnt and HIF1 dual signaling inhibitory activity at 5 μmol/L than the positive control, which offers an exciting starting point for further investigations. All stereoisomers significantly promoted angiogenesis and showed moderate anti‐inflammation in zebrafish. A quantum chemical calculation and deuteration experiment were applied to unveil the reaction mechanism which guides the synthesis of the target compounds.

Design, Synthesis, and Biological Activity of Guaiazulene Derivatives

“…PPARγ is a primary factor of the accumulation and phenotype of adipose tissue T reg cells leading obesity and other diseases [29] and PPARγ signaling pathway also plays a certain role in the sensitivity of insulin [30] . Flavonoids found in many fruits and vegetables have been revealed to display agonist effects on PPARγ signaling pathway [21,22] .…”

“…PPARγ is a primary factor of the accumulation and phenotype of adipose tissue T reg cells leading obesity and other diseases [29] and PPARγ signaling pathway also plays a certain role in the sensitivity of insulin. [30] Flavonoids found in many fruits and vegetables have been revealed to display agonist effects on PPARγ signaling pathway. [21,22] A reporter assay using Gal4-PPARγ ligand-binding domain (LBD) expression plasmid [31] was utilized to evaluate human PPARγ signaling pathway agonistic effect of guaiazulene based flavonoids (series IV) in Chang liver cells at the concentration of 20 μM using rosiglitazone as positive control.…”

“…The relative fluorescence activity is expressed as the ratio of the treatment group data and the control group data. [30] Drug-Likeness Properties SwissADME (http://www.swissadme.ch) predictions were used to describe the drug likeness for each final compound. The physicochemical properties comprise typical molecular characteristics, including TPSA (Topological Polar Surface Area).…”

Sinudenoids A–E, C19-Norcembranoid Diterpenes with Unusual Scaffolds from the Soft Coral Sinularia densa

“…They were thought to originate from the common C 19norcembranoid diterpene precursor, norrubifolide, through different cyclization processes. 12,13 In our continuing search for new bioactive metabolites from marine invertebrates, 14,15 the first systematic investigation for the soft coral Sinularia densa collected off the Xisha Islands (Paracel Islands) resulted in the isolation of four unprecedented furanobutenolide-derived C 19 -norcembranoids, sinudenoids A− D (1−4, respectively) with three different types of carbon scaffolds, one rare 8/8 bicyclic sinudenoid E (5), and four known related compounds, sinuscalide A (6), 16 5-episinuleptolide (7), 17 scabrolide B (8), 18 and scabrolide A (9) (Figure 1). 18 The first analogue of sinudenoid E (5) as a co-isolate in this work, sinuscalide A (6), was just published in July 2022.…”

Structural Investigation of Aaptourinamine by a Novel Module-Assembly-Based Calculation

“…The following supporting information can be downloaded at: . Figure S1: Core structures A–D for aaptourinamine; Figure S2: The counting principle of the connection site; Figures S3–S5: The meta-structures for the core structure A–C; Figures S6–S12: Spectra for aaptourinamine; Table S1: The Computational details of the 150 structures [ 35 ]; Table S2: 1D and key 2D NMR data of aaptourinamine; Supplementary Data S1: Five kinds of energies calculated for aaptourinamine.…”