Anticancer Activities of Six Selected Natural Compounds of Some Cameroonian Medicinal Plants

BACKGROUND: Natural products are well recognized as sources of drugs in several human ailments. In the present work, we carried out a preliminary screening of six natural compounds, xanthone V(1) (1); 2-acetylfuro-1,4-naphthoquinone (2); physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were then tested in several other cancer cells and their possible mode of action were investigated. METHODOLOGY/FINDINGS: The tested compounds were previously isolated from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a panel of cancer cell lines. The study was also extended to the analysis of cell cycle distribution, apoptosis induction, caspase 3/7 activation and the anti-angiogenic properties of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone. IC(50) values around or below 4 µg/ml were obtained on 64.29% and 78.57% of the tested cancer cell lines for xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, respectively. The most sensitive cell lines (IC(50)<1 µg/ml) were breast MCF-7 (to xanthone V(1)), cervix HeLa and Caski (to xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone), leukemia PF-382 and melanoma colo-38 (to 2-acetylfuro-1,4-naphthoquinone). The two compounds showed respectively, 65.8% and 59.6% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail eggs in the anti-angiogenic assay. Upon treatment with two fold IC(50) and after 72 h, the two compounds induced cell cycle arrest in S-phase, and also significant apoptosis in CCRF-CEM leukemia cells. Caspase 3/7 was activated by xanthone V(1). CONCLUSIONS/SIGNIFICANCE: The overall results of the present study provided evidence for the cytotoxicity of compounds xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, and bring supportive data for future investigations that will lead to their use in cancer therapy

A NEW SOURCE OF KOJIC ACID ISOLATED FROM KIGELIA AFRICANA: A POSSIBLE PRECURSOR FOR QUINONE BIOSYNTHESIS

ABSTRACT Kojic acid (5-hydroxy-2-hydroxymethyl-γ-pyrone) a fungal metabolite produced by Aspergillus spp., Penicillium spp. and belonging mainly to the flavus-oryzaetamarii groups was isolated for the first time from Kigelia africana as the major constituent by mass fragmentation guided isolation. From a biosynthetic consideration, Kojic acid is a possible intermediate in the synthesis of the quinone scaffolds

Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other naphthoquinone derivatives from lapachol

Ozonolysis of lapachol (1), resulting in an unusual formation of a potent antitumor agent 2-acetylfuranonaphthoquinone (3) along with the expected aldehyde 6, is described. The reaction of lapachol (1) with CAN in dry acetonitrile leading to biologically active furanonaphthoquinones is also reported. The antitumoral activity of the tested compounds on human DU-145 prostate carcinoma cells was evaluated following XTT assay. The results revealed that 2-(1-methylethenyl)-2,3-dihydronaphtho[2,3-b]furan-4,9-dione (5), β-lapachone (10) and dehydro-β-lapachone diacetate (11) showed 100% inhibition at 25 μg/ml. All the tested samples showed dose-dependent activity

A mechanistic study on the Hooker oxidation: synthesis of novel indane carboxylic acid derivatives from lapachol

The Hooker oxidation is one of the most intriguing transformations wherein lapachol (1) is readily converted to norlapachol (2) in very good yield. This one-pot reaction involves a very intricate mechanism in which the alkyl side chain of lapachol is shortened by one carbon unit. Previous studies have unequivocally established the involvement of an indane carboxylic acid derivative 3, as a key intermediate (Hooker intermediate), and its simultaneous conversion to norlapachol (2) via the oxidative cleavage of vicinol diol and subsequent intramolecular aldol reaction of the resulting keto acid. However, the formation of the key Hooker intermediate 3 from lapachol (1) remains ambiguous. The present study has thrown some light on the formation of the key intermediate 3 from lapachol (1) via benzilic acid rearrangement of the corresponding labile o-diquinone intermediate 8 derived from lapachol. The involvement of o-diquinone intermediate 8 in the Hooker oxidation has been further established by trapping of this labile intermediate as the corresponding phenazine derivative 9. The involvement of benzilic acid rearrangement as a key step in the Hooker oxidation is further shown with a variety of o-quinones prepared from lapachol (1)

Lipoxygenase inhibition and molecular docking studies of secondary metabolites from the leaves of Alstonia scholaris

The phytochemical study was carried out on the ethanolic extract of the leaves of Alstonia scholaris. This plant has been used traditionally for medicinal purposes in the treatment of several diseases such as cancer, jaundice, malaria, gastrointestinal troubles, dysentery, snake-bite and diarrhea. Chromatographic purification of this extract led to the isolation and characterization of nine compounds. Their structures were elucidated as betulin (1), α-amyrin acetate (2), mixture of β-sitosterol (3) and stigmasterol (4), tetratriacontyl-trans-p-coumarate (5), ursolic acid (6), picralstonine (7), β-sitosterol glucoside (8) and scholaricine (9). Scholaricine and β-sitosterol-glucoside exhibited potent lipoxygenase inhibitory activity with IC50 of 15.2 ​± ​0.41 and 18.5 ​± ​0.14 respectively compared to Baicalein (22.6 ​± ​0.08) used as positive control. Molecular docking studies were conducted to support lipoxygenase inhibitory activities of the test compounds

Cobalt mediated ring contraction reaction of lapachol and initial antibacterial evaluation of naphthoquinones derived from lapachol

The synthesis of 2-hydroxy-2-(3-methylbut-2-enyl)-2H-indene-1,3-dione 3, from lapachol which involves a ring contraction via the Hooker intermediate 1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylic acid 2 is described. Different pyranonaphthoquinone derivatives, obtained in our previous synthetic work, were screened for antimycobacterial (Mycobacterium tuberculosis) activity and against resistant strains of Gram-positive (Bacillus cereus and Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The results indicated significant activity of all the tested samples against M. tuberculosis and only moderate activity against the Gram-positive and Gram-negative bacteria

Bioactive Seco-Lanostane-Type Triterpenoids from the Roots of <i>Leplaea mayombensis</i>

Fractionation of the ethyl acetate-soluble extract of the roots of <i>Leplaea mayombensis</i> afforded two new 3,4-seco-lanostane-type triterpenoids, leplaeric acids A and B (<b>1</b>, <b>2</b>), the new lanostane-type triterpenoid leplaeric acid C (<b>3</b>), and six known natural products (<b>5</b>–<b>10</b>). Derivatization of the main constituent, <b>1</b>, afforded the dimethyl ester <b>4</b>, the monoamide <b>11</b>, and diamide <b>12</b> for SAR studies. The structures of these compounds were established through spectroscopic methods, and a single-crystal X-ray diffraction analysis was used to confirm the relative configuration of compound <b>1</b>. These lanostane derivatives are unique since they are the first C-21-oxygenated lanostanes isolated from plant sources. Preliminary biological assays against the MDA MB 231 breast cancer cell line showed that compounds <b>1</b>, <b>2</b>, <b>4</b>, and <b>11</b> have modest cytotoxic activity. Compound <b>2</b> was the most active, with an IC₅₀ of 55 ± 7 μM. From these results, the amides (<b>11</b>, <b>12</b>) derived from triterpenoid <b>1</b> were found to be less active than the derived esters (<b>2</b>, <b>4</b>)

Cytotoxicity of compounds <b>1</b>, <b>2</b> and doxorubicin on different cancer cell lines.

<p>*EC₅₀: effective dose showing 50% inhibition of growth proliferation.</p

Cell cycle distribution with Leukemia CCRF-CEM treated with compounds 2.

<p><b>A1</b>: control after 24 h; <b>A2</b>: control after 48 h; <b>A3</b>: control after 72 h; <b>B1</b>: treated with 2×IC₅₀ after 24 h; <b>B2</b>: treated with 2×IC₅₀ after 48 h; <b>B3</b>: treated with 2×IC₅₀ after 72 h; <b>C1</b>: treated with 2×IC₅₀ after 24 h; <b>C2</b>: treated with 2×IC₅₀ after 48 h; <b>C3</b>: treated with 2×IC₅₀ after 72 h; <b>D1</b>: treated with 2×IC₅₀ after 24 h; <b>D2</b>: treated with 2×IC₅₀ after 48 h; <b>D3</b>: treated with 2×IC₅₀ after 72 h.</p