Incorporation of Privileged Structures into Bevirimat Can Improve Activity against Wild-Type and Bevirimat-Resistant HIV‑1

Two “privileged fragments”, caffeic acid and piperazine, were integrated into bevirimat producing new derivatives with improved activity against HIV-1/NL4-3 and NL4-3/V370A carrying the most prevalent bevirimat-resistant polymorphism. The activity of one of these, <b>18c</b>, was increased by 3-fold against NL4-3 and 51-fold against NL4-3/V370A. Moreover, <b>18c</b> is a maturation inhibitor with improved metabolic stability. Our study suggested that integration of privileged motifs into promising natural product skeletons is an effective strategy for discovering potent derivatives

Vitepyrroloids A–D, 2‑Cyanopyrrole-Containing Labdane Diterpenoid Alkaloids from the Leaves of <i>Vitex trifolia</i>

Vitepyrroloids A–D (<b>1</b>–<b>4</b>), four new 2-cyano-substituted pyrrole-ring-containing labdane diterpenoids, were isolated from the leaves of <i>Vitex trifolia</i>. Their structures were elucidated based on spectroscopic data analysis. The absolute configuration of compound <b>1</b> was determined by X-ray diffraction. Compounds <b>1</b>–<b>4</b> are unprecedented labdane diterpenoids featuring a 2-cyano-substituted pyrrole ring. Compound <b>1</b> showed cytotoxic activity against a human nasopharyngeal carcinoma cell line (CNE1) with an IC₅₀ value of 8.7 μM

Songaricalarins A–E, Cytotoxic Oplopane Sesquiterpenes from <i>Ligularia songarica</i>

Five new highly oxygenated oplopane sesquiterpenes, songaricalarins A–E (<b>1</b>–<b>5</b>), and two known analogues (<b>6</b> and <b>7</b>) were isolated from the roots and rhizomes of <i>Ligularia songarica</i>. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques, and the structure of <b>1</b> was confirmed by single-crystal X-ray diffraction. All compounds were evaluated for in vitro cytotoxic activity against cultured A-549, MCF-7, KB, and KBVIN cells, and <b>4</b> exhibited cytotoxicity with EC₅₀ values of 4.9, 0.8, 3.4, and 3.2 μg/mL, respectively

Vitepyrroloids A–D, 2‑Cyanopyrrole-Containing Labdane Diterpenoid Alkaloids from the Leaves of <i>Vitex trifolia</i>

Vitepyrroloids A–D (<b>1</b>–<b>4</b>), four new 2-cyano-substituted pyrrole-ring-containing labdane diterpenoids, were isolated from the leaves of <i>Vitex trifolia</i>. Their structures were elucidated based on spectroscopic data analysis. The absolute configuration of compound <b>1</b> was determined by X-ray diffraction. Compounds <b>1</b>–<b>4</b> are unprecedented labdane diterpenoids featuring a 2-cyano-substituted pyrrole ring. Compound <b>1</b> showed cytotoxic activity against a human nasopharyngeal carcinoma cell line (CNE1) with an IC₅₀ value of 8.7 μM

Taburnaemines A–I, Cytotoxic Vobasinyl-Iboga-Type Bisindole Alkaloids from <i>Tabernaemontana corymbosa</i>

Nineteen vobasinyl-ibogan-type bisindole alkaloids, including nine new compounds, taburnaemines A–I (<b>1</b>–<b>9</b>), were isolated from the twigs and leaves of <i>Tabernaemontana corymbosa</i>. The structures and absolute configurations of the new alkaloids were determined by a combination of MS, NMR, and ECD analyses. Alkaloids <b>1</b>–<b>5</b> contain a rare 1,3-oxazinane moiety in the vobasinyl unit, while <b>6</b> has an uncommon 1,3-oxazolidine moiety in the iboga unit. The absolute configurations of alkaloid <b>1</b> and the known alkaloid tabernaecorymbosine A (<b>10</b>) were confirmed by single-crystal X-ray diffraction analysis. All of the bisindole alkaloids, except <b>2</b> and 16′-decarbomethoxy­tabernaecorymbosine A (<b>14</b>), showed antiproliferative activity (IC₅₀ 2.6–9.8 μM) against several human cancer cell lines, including A-549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrug-resistant KB cells. The preliminary structure–activity relationship correlations are also discussed

Taburnaemines A–I, Cytotoxic Vobasinyl-Iboga-Type Bisindole Alkaloids from <i>Tabernaemontana corymbosa</i>

Nineteen vobasinyl-ibogan-type bisindole alkaloids, including nine new compounds, taburnaemines A–I (<b>1</b>–<b>9</b>), were isolated from the twigs and leaves of <i>Tabernaemontana corymbosa</i>. The structures and absolute configurations of the new alkaloids were determined by a combination of MS, NMR, and ECD analyses. Alkaloids <b>1</b>–<b>5</b> contain a rare 1,3-oxazinane moiety in the vobasinyl unit, while <b>6</b> has an uncommon 1,3-oxazolidine moiety in the iboga unit. The absolute configurations of alkaloid <b>1</b> and the known alkaloid tabernaecorymbosine A (<b>10</b>) were confirmed by single-crystal X-ray diffraction analysis. All of the bisindole alkaloids, except <b>2</b> and 16′-decarbomethoxy­tabernaecorymbosine A (<b>14</b>), showed antiproliferative activity (IC₅₀ 2.6–9.8 μM) against several human cancer cell lines, including A-549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrug-resistant KB cells. The preliminary structure–activity relationship correlations are also discussed

Tabercorymines A and B, Two Vobasinyl–Ibogan-Type Bisindole Alkaloids from Tabernaemontana corymbosa

Tabercorymines A (<b>1</b>) and B (<b>2</b>), two new vobasinyl–ibogan-type bisindole alkaloids with an unprecedented skeleton, were isolated from Tabernaemontana corymbosa. Their structures were established by a combination of spectroscopic data, chemical transformation, single-crystal X-ray diffraction, and ECD calculation. Compound <b>1</b> represents a novel bisindole alkaloid, characterized by a caged heteropentacyclic ring system incorporating an unprecedented C-7/C-20 bond in the vobasinyl unit. Alkaloids <b>1</b> and <b>2</b> showed potent antiproliferative activity against several human cancer cell lines, including vincristine-resistant KB

Indole Alkaloid Glycosides from the Aerial Parts of <i>Strobilanthes cusia</i>

Three indole alkaloid glycosides, strobilanthosides A–C (<b>1</b>–<b>3</b>), two known indole alkaloid glucosides (<b>4</b> and <b>5</b>), and five phenylethanoid glycosides (<b>8</b>–<b>10</b>) were isolated from the aerial parts of <i>Strobilanthes cusia</i>. The structures of the new compounds were elucidated by spectrometric analysis, and the absolute configurations of <b>1</b> and <b>2</b> were established by ECD spectrocsopy. <i>N</i>′-β-d-Glucopyranosylindirubin (<b>5</b>) showed weak antibacterial activity (MIC 62.5–125 μM) against <i>Staphylococcus aureus</i>

Novel HIV‑1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus

Three series (<b>6</b>, <b>13</b>, and <b>14</b>) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new-generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (<b>1b</b>). Promising new compounds were then assessed for physicochemical and associated pharmaceutical properties, including aqueous solubility, log P value, and metabolic stability, as well as predicted lipophilic parameters of ligand efficiency, ligand lipophilic efficiency, and ligand efficiency-dependent lipophilicity indices, which are associated with ADME property profiles. Compounds <b>6a</b>, <b>14c</b>, and <b>14d</b> showed high potency against the <b>1b</b>-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties. From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R¹ group might provide greater efficacy against the E138K mutant

Two new cadinane-type sesquiterpenes from the Chinese liverwort <i>Frullania serrata</i>

<div><p>Two new cadinane-type sesquiterpenes, frullanic acid (<b>1</b>) and frullanic acid methyl ester (<b>2</b>), together with four known bibenzyls, brittonin B (<b>3</b>), 3,3′-dimethoxy-4,5-methylenedioxybibenzyl (<b>4</b>), 3,4,5,3′,4′-penlamethoxybibenzyl (<b>5</b>) and ( ± )-3-(4′-methoxybenzyl)-5,6-dimethoxyphtbalide (<b>6</b>), were isolated from the Chinese liverwort <i>Frullania serrata</i>. The structures of the new metabolites were elucidated by analysing the spectroscopic data (1D NMR, 2D NMR, HR-ESI-MS and IR). The absolute configurations of compounds <b>1</b> and <b>2</b> were determined by comparing the experimental and calculated electronic circular dichroism spectra predicted by using time-dependent density functional theory as well as the CD exciton chirality method.</p></div