Conofolidine: A Natural Plant Alkaloid That Causes Apoptosis and Senescence in Cancer Cells.

Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel bisindole alkaloid isolated from the Malayan plant . Herein, we report conofolidine's broad-spectrum anticancer activity together with that of three other bisindoles-conophylline, leucophyllidine, and bipleiophylline-against human-derived breast, colorectal, pancreatic, and lung carcinoma cell lines.

Correction to "Apoferritin-Encapsulated Jerantinine A for Transferrin Receptor Targeting and Enhanced Selectivity in Breast Cancer Therapy".

[This corrects the article DOI: 10.1021/acsomega.2c00997.

Asymmetric Synthesis of Arboduridine.

The first asymmetric total synthesis of the monoterpenoid indole alkaloid arboduridine has been accomplished. The tricyclic A/B/D ring system was constructed by an enantioselective Michael reaction followed by intramolecular nucleophilic addition. Intramolecular α-amination of a ketone forged the piperidine ring, while a Horner-Wadsworth-Emmons (HWE) reaction was used to form the pyrrolidine ring.

Vobasine, vincamine, voaphylline, tacaman, and iboga alkaloids from Tabernaemontana corymbosa.

Thirteen indole alkaloids comprising six vobasine/sarpagine, one vincamine, two voaphylline, two tacaman, one iboga, and one corynantheine alkaloid, were isolated from the leaf extract of Tabernaemontana corymbosa (sample from Taiping, Perak, Malaysia). The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and MS), and in the case of vincarudine, the absolute configuration was established by ECD and X-ray diffraction analysis. Vobasidine E represents the first vobasine-type alkaloid characterized by a contracted ring C and loss of the ethylidene/ethyl side chain.

Apoferritin-Encapsulated Jerantinine A for Transferrin Receptor Targeting and Enhanced Selectivity in Breast Cancer Therapy.

The O-acetyl (or acetate) derivative of the Aspidosperma alkaloid Jerantinine A (JAa) elicits anti-tumor activity against cancer cell lines including mammary carcinoma cell lines irrespective of receptor status (0.14 < GI < 0.38 μM), targeting microtubule dynamics.

Divergent Synthesis of Skeletally Distinct Arboridinine and Arborisidine.

A divergent synthesis of skeletally distinct arboridinine and arborisidine was achieved. The central divergent strategy was inspired by the divergent biosynthetic cyclization mode of arboridinine and arborisidine and their hidden topological connection. The branch point was reached through a Michael and Mannich cascade process.

The Bisindole Alkaloids Angustilongines M and A from Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization.

A new linearly fused macroline-sarpagine bisindole, angustilongine M (), was isolated from the methanolic extract of . The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (). Compounds and showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines.

Concise synthesis of the vasorelaxant alkaloids schwarzinicines A and B.

A concise synthesis of the 1,4-diarylbutanoid-phenethylamine alkaloids, schwarzinicines A () and B (), recently isolated from , is reported. Key steps include a Claisen condensation to assemble the 1,4-diaryl-2-butanone intermediate, followed by a reductive amination to furnish the core skeleton of the target compounds. The overall synthetic yields of and were 9.

The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun.

Background: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells.

Macroline, talpinine, and sarpagine alkaloids from Alstonia penangiana. An NMR-based method for differentiating between A. penangiana and A. macrophylla.

Fourteen previously undescribed alkaloids comprising two N-1-hydroxymethylmacroline alkaloids, one talpinine-type oxindole acetal, a pair of equilibrating talpinine-type oxindole hemiacetals, eight oxidized derivatives of sarpagine- and akuammiline-type indole alkaloids, in addition to alstochalotine a diastereomer of gelsochalotine recently isolated from Gelsemium elegans, were isolated from the leaf and stem-bark extracts of Alstonia penangiana. The structures and relative configurations of these alkaloids were established using NMR, MS, and in one instance, confirmed by X-ray diffraction analysis. An NMR-based method is described as a useful chemotaxonomic tool for differentiating between A.

Macroline-Sarpagine Bisindole Alkaloids with Antiproliferative Activity from .

A methanol extract of the stem bark of the Malayan provided seven new bisindole alkaloids, comprising six macroline-sarpagine alkaloids (angustilongines E-K, -) and one macroline-pleiocarpamine bisindole alkaloid (angustilongine L, ). Analysis of the spectroscopic data (NMR and MS) of these compounds led to the proposed structures of these alkaloids. The macroline-sarpagine alkaloids (-) showed in vitro growth inhibitory activity against a panel of human cancer cell lines, inclusive of KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells (IC values: 0.

A Cytotoxic Indole Characterized by Incorporation of a Unique Carbon-Nitrogen Skeleton and Two Pentacyclic Corynanthean Alkaloids Incorporating a Substituted Tetrahydrofuranone Ring from .

Three new alkaloids were isolated from the bark extract of the Malayan , viz., arbophyllidine (), an unusual pentacyclic, monoterpenoid indole characterized by an absence of oxygen atoms and incorporating a new carbon-nitrogen skeleton, and arbophyllinines A () and B (), two pentacyclic corynanthean alkaloids incorporating a hydroxyethyl-substituted tetrahydrofuranone ring. The structures of the alkaloids were deduced based on analysis of the MS and NMR data and confirmed by X-ray diffraction analyses.

Reactions of Anodically Generated Methoxystilbene Cation Radicals: The Influence of Ortho-Substituted Vinyl and Formyl Groups.

The present investigation represents a continuation of studies on the effect of ortho'-substitution on the reactivity of anodically generated methoxystilbene cation radicals. Whereas previous studies have focused on the effect of ortho'-substituted nucleophilic groups such as OH, NH, CHOH, CHNH, and COOH, the present study extends the investigation to ortho'-substituted vinyl and formyl groups. The results show that when the ortho'-substituent is a vinyl group, the products include a bisdihydronaphthalene derivative and a doubly bridged, dibenzofused cyclononane from direct trapping of a bis carbocation intermediate.

Conolodinines A-D, Aspidosperma- Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa.

Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1-4) and two known bisindole alkaloids (5, 6) of the Aspidosperma- Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). X-ray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations.

Lycopodium Alkaloids: Lycoplatyrine A, an Unusual Lycodine-Piperidine Adduct from Lycopodium platyrhizoma and the Absolute Configurations of Lycoplanine D and Lycogladine H.

Three new Lycopodium alkaloids comprising two lycodine-type alkaloids (1, 2) and one fawcettimine alkaloid (3), in addition to 16 known alkaloids, were isolated from Lycopodium platyrhizoma. The structures of these alkaloids were elucidated based on analysis of their NMR and MS data. Lycoplatyrine A (1) represents an unusual lycodine-piperidine adduct.

Reactivity of Anodically Generated 4-Methoxystilbene Cation Radicals: The Influence of Ortho-Substituted Hydroxymethyl, Aminomethyl, and Carboxylic Acid Groups.

The effect of ortho'-substituted side chains bearing nucleophilic groups such as CHOH, CHNHR, and COH on the reactivity of anodically generated 4-methoxy- and 3,4-dimethoxystilbene cation radicals was investigated, and results were compared with those of substrates where the nucleophilic groups such as OH and NHR are directly attached to the aromatic ring. It was found that when ortho'-substituted groups such as CHOH or CHNHR are present in the other ring, only direct intramolecular cation-nucleophile reactions occur to give bisbenzopyrans or bisisoquinolines. Crossover products (previously obtained when the ortho' substituents were OH and NH) such as the fused benzoxepanes/fused benzoazepanes were not formed.

Sustainable Syntheses of (-)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site.

The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature.

Ajmaline, Oxindole, and Cytotoxic Macroline-Akuammiline Bisindole Alkaloids from Alstonia penangiana.

Examination of the EtOH extract of the Malayan Alstonia penangiana resulted in the isolation of 10 new alkaloids, comprising two ajmaline (1, 2), four macroline oxindole (3-6), and four macroline-akuammiline bisindole alkaloids (7-10). The structures of these alkaloids were determined based on analysis of the spectroscopic data and, in the case of the oxindole 6 and the bisindole alkaloid 7, also confirmed by X-ray diffraction analysis. The bisindole alkaloids 7 and 8 showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells with IC values in the 0.

Biosynthetic Enantiodivergence in the Eburnane Alkaloids from Kopsia.

Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K.

A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from Ficus fistulosa var. tengerensis.

Tengerensine (1), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (2), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of Ficus fistulosa var. tengerensis, along with three other known alkaloids. The structures of 1 and 2 were determined by spectroscopic data interpretation and X-ray diffraction analysis.

Electrochemically Mediated Oxidative Transformations of Substituted 4-Methoxystilbenes: Effect of Ortho-Substituted Nucleophilic Groups.

A systematic study was undertaken to determine the influence of ortho'-substituted nucleophilic groups (OH, NH, or NHR) on the reactivity of anodically generated 4-methoxy- and 3,4-dimethoxystilbene cation radicals. The results showed that when ortho-substituted nucleophilic groups such as OH and NHR are present in the other ring, both direct and crossover intramolecular cation-nucleophile reactions occur to give bisbenzofurans/bisindoles or fused bisbenzopyrans/bisquinolines, respectively. Where an additional 3-methoxy substituent is present, bridged oxocine/azocine products are formed in addition to the bisbenzopyrans/bisquinolines and bisbenzofurans/bisindoles.

Enhancement of apoptotic activities on brain cancer cells via the combination of γ-tocotrienol and jerantinine A.

Background: γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities.

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1).

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents.