Susan L. Morris-Natschke

HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3′,3′-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat. To ascertain the binding modes of this derivative, further modification of compound 1 was conducted. Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted. Five new derivatives were synthesized, among which compound 3b showed significant activity against HIV-1_NL4-3 with an EC₅₀ value of 0.28 µM. The developed 3D-QSAR model resulted in great predictive ability with training set (r² = 0.99, q² = 0.55). Molecular docking studies were complementary to the 3D-QSAR analysis, showing that DSC was differently bound to CA-SP1 with higher affinity than that of bevirimat. MD studies revealed that the complex of the ligand and the protein was stable, with root mean square deviation (RMSD) values <2.5 Å. The above results provided valuable insights into the potential of DSC as a prototype to develop new antiviral agents.

Two new carbazole alkaloids (1,2) and six known carbazole alkaloids (3–8) were isolated from Clausena anisum-olens. Their structures were elucidated based on extensive spectroscopic analysis. All isolated compounds (1–8) were evaluated for their anti-HIV effects on virus replication in MT-4 lymphocytes infected by HIV-1_NL4-3 Nanoluc-sec virus, and new carbazole alkaloid 1 exhibited anti-HIV activity with an EC₅₀ value of 2.4 μg/mL and SI of 7.1.

Following publication of the original article [1], the authors reported an error in Schemes 1 and 2 and repeated line in subsection “Bis(ligand) nickel(II) chelate (NiL1₂)”.

Six new dammarane-type saponins, gypenosides CP1-6 (1–6), along with 19 known compounds 7–25, were isolated and characterized from the aerial parts of Gynostemma pentaphyllum. Among these compounds, eight dammarane-type saponins, 2, 5, 6, 7, 11, 12, 13, and 15, exhibited the greatest antiproliferative effects against two human tumor cell lines (A549 and HepG2).

Background: The general approach to the synthesis of metal complexes begins with ligand synthesis, followed by ligand reaction with metal salts to afford organometallic complexes. Our research group first reported a one-pot multicomponent synthesis of chiral oxazolinyl–zinc complexes, in the presence of a large amount of ZnCl₂ (0.4–2.6 equiv.), with the yields of some products reaching 90%. Results: Our prior strategy was extended to use copper, cobalt, nickel, manganese, palladium or platinum salts as the third component. The one-step method used 1.0 equivalent of a metal salt, such as M(OAc)₂·nH₂O or MCl₂·nH₂O (M: Cu, Co, Ni, Pd or Pt, n = 1, 2 or 4), as a reagent to generate chiral salicyloxazoline complexes 1–8 in the reaction of 2-cyanophenol with different d- and l-amino alcohols. Conclusion: Complexes 1–8 were obtained using a one-pot method with a sequential strategy. The reaction outcome was demonstrated for three-component reactions between metal salts, amino alcohols and 2-hydroxybenzonitrile to afford organometallic complexes in good yields (65–95%).