Mono-tetrahydrofuran Annonaceous Acetogenins from <i>Annona squamosa</i> as Cytotoxic Agents and Calcium Ion Chelators

Eight new mono-tetrahydrofuran (THF)-type annonaceous acetogenins, squafosacins B, C, F, and G (1−4), squadiolins A−C (5−7), and cis-annotemoyin-1 (8), as well as eight known annonaceous acetogenins, glabranin, annotemoyins-1 and -2, bullatencin, cis-bullatencin, and uvariamicins-I, -II, and -III, were isolated from the seeds of Annona squamosa by HPLC. The structures of all new isolates were elucidated by using spectroscopic and chemical methods. Squadiolins A (5) and B (6) showed ng/mL potency against human Hep G2 hepatoma cells and significant cytotoxic activity against human MDA-MB-231 breast cancer cells. Squafosacin B (1) also exhibited significant cytotoxic activity against human Hep G2 and 3B hepatoma and MCF-7 breast cancer cells. In addition, the chelation of mono-THF acetogenins with calcium ions was investigated using isothermal titration calorimetry

Cytotoxicity data of natural phenanthrenes isolated from <i>C. arisanensis</i>.

a<p>Doxorubicin (Doxo) was used as the positive control.</p

Cytotoxic Triterpenoids from the Leaves of <i>Microtropis fokienensis</i>

Five new triterpenoids, microfokienoxanes A−D (1−4) and 3β,28-dihydroxy-11α-methoxyurs-12-ene (5), were isolated and identified from the leaves of Microtropis fokienensis, along with nine known compounds. The structures of the new compounds were elucidated by spectroscopic methods. The compounds obtained in this investigation were evaluated against a small panel of human cancer cell lines for cytotoxicity. Only compounds 3 and 5 exhibited cytotoxicity (IC50 ≤ 5 μg/mL) for one or more cell lines

Structural sets used in the pharmacophore study.

<p>CA-1∼CA-11 and 3a-9b are noted as natural and synthesized compounds, respectively.</p

Synthetic procedure of phenanthrene derivatives.

<p>Reagents and conditions: (i) DDQ, benzene, RT. (ii) TFA, ether, RT. (iii) Me₂SO₄, K₂CO₃, acetone, reflux. (iv) P₄-<i>t</i>Bu, benzene, 140°C. (v) AgO, 6 N HNO₃, acetone, 60°C.</p

Cytotoxicity data of synthesized phenanthrenes.

a<p>Doxorubicin (Doxo) was used as the positive control.</p

Structures of calanquinone A and denbinobin.

<p>Structures of calanquinone A and denbinobin.</p

Selective demethylation and acetylation of phenanthrenequinones.

<p>Reagents and conditions: (i) TMSI, CH₂Cl₂, RT or 60°C. (ii) Ac₂O, pyridine, RT.</p

Cytotoxic Triterpenoids from the Leaves of <i>Microtropis fokienensis</i>

Five new triterpenoids, microfokienoxanes A−D (1−4) and 3β,28-dihydroxy-11α-methoxyurs-12-ene (5), were isolated and identified from the leaves of Microtropis fokienensis, along with nine known compounds. The structures of the new compounds were elucidated by spectroscopic methods. The compounds obtained in this investigation were evaluated against a small panel of human cancer cell lines for cytotoxicity. Only compounds 3 and 5 exhibited cytotoxicity (IC50 ≤ 5 μg/mL) for one or more cell lines

ChemGPS-NP analysis of calanquinone A (6a) and denbinobin (6b).

<p>Score plot of the three dimensions (principal components 2–4) consisting of PC2 (yellow; aromaticity etc.), PC3 (green; lipophilicity etc.) and PC4 (orange; flexibility/rigidity), from analysis of most potent compounds <b>6a</b> and <b>6b</b> as medium seagreen cubes in the ChemGPS-NP model addressed by Rosén et al. in 2009 for prediction of MOA. A reference set of known anticancer agents includes alkylating agents (red), anti-metabolites (lime), proteasome inhibitions (cyan), tyrosine kinase inhibitors (orange), topoisomerase I (blue), topoisomerase II (magenta), and tubulin inhibitors (black).</p