Muricoreacin and murihexocin C, mono-tetrahydrofuran acetogenins, from the leaves of Annona muricata.

Bioactivity-directed fractionation of the leaves of Annona muricata L. (Annonaceae) resulted in the isolation of two new Annonaceous acetogenins, muricoreacin (1) and murihexocin C (2). Compounds 1 and 2 showed significant cytotoxicities among six human tumor cell lines with selectivities to the prostate adenocarcinoma (PC-3) and pancreatic carcinoma (PACA-2) cell lines.

Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin, from the leaves of Annona muricata.

Bioactivity-directed fractionation of the leaf extract of Annona muricata L. (Annonaceae) has resulted in the isolation of two new Annonaceous acetogenins, annomuricine (1) and muricapentocin (2). Compounds 1 and 2 are monotetrahydrofuran ring acetogenins bearing two flanking hydroxyl groups; however, each has three additional hydroxyl groups. Compound 1 has an erythro 1,2-diol, and 2 has a 1,5,9-triol moiety. Both 1 and 2 showed significant cytotoxicities against six types of human tumors, with selectivities to the pancreatic carcinoma (PACA-2) and colon adenocarcinoma (HT-29) cell lines.

Additional bioactive acetogenins, annomutacin and (2,4-trans and cis)-10R-annonacin-A-ones, from the leaves of Annona muricata.

In a continuation of our research on bioactive components from the leaves of Annona muricata, three novel monotetrahydrofuran Annonaceous acetogenins, namely, annomutacin [1], (2,4-trans)-10R-annonacin-A-one [2], and (2,4-cis)-10R- annonacin-A-one [3], have been identified. Their structures were deduced by ms, nmr, ir, and uv spectral and chemical methods, and the absolute configurations were determined by Mosher ester methodology. A known bioactive amide, N-p-coumaroyl tyramine, was also found. Compound 1 and the mixture of compounds 2 and 3 showed selective cytotoxicities against the human A-549 lung tumor cell line.

Two new cytotoxic monotetrahydrofuran Annonaceous acetogenins, annomuricins A and B, from the leaves of Annona muricata.

The leaves of Annona muricata have yielded eight monotetrahydrofuran Annonaceous acetogenins. Two of them, annomuricins A [1] and B [2], whose chemical structures were deduced by ms, nmr, ir, and uv spectral and chemical methods, are novel and unusual. Compounds 1 and 2 each possess five hydroxyl groups; two hydroxyl groups are vicinal, with the vicinal group of 1 threo and that of 2 erythro. The absolute configurations of 1 and 2 were determined by Mosher ester methodology. Six monotetrahydrofuran acetogenins, previously described in the seeds, were found in the leaves; these are gigantetrocin A, annonacin-10-one, muricatetrocins A and B, annonacin, and goniothalamicin.

Muricatocins A and B, two new bioactive monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata.

The leaves of Annona muricata have yielded the novel monotetrahydrofuran Annonaceous acetogenins, muricatocins A [1] and B [2]. Each compound possesses five hydroxyl groups, with two hydroxyl groups at the C-10 and C-12 positions. The absolute configurations of 1 and 2 (except for positions C-10 and C-12) were determined by Mosher ester methodology. The C-10, C-12 acetonides (1c, 2c) suggested relative stereochemistry and significantly enhanced cytotoxicity against the A-549 human lung tumor cell line. Three known monotetrahydrofuran acetogenins, annonacin A, (2,4-trans)-isoannonacin, and (2,4-cis)-isoannonacin, were also found.

New bioactive monotetrahydrofuran Annonaceous acetogenins, annomuricin C and muricatocin C, from the leaves of Annona muricata.

The leaves of Annona muricata have yielded two additional monotetrahydrofuran Annonaceous acetogenins, annomuricin C [1] and muricatocin C [2]. Compounds 1 and 2 each possess five hydroxyl groups; two hydroxyl groups are at the C-10/C-11 and C-10/C-12 positions in 1 and 2, respectively. The absolute configurations of 1 and 2, except for positions C-10 and C-11 or C-12, were determined by Mosher ester methodology. The C-10/C-11 and C-10/C-12 acetonides (1c, 2c) suggested relative stereochemistry and significantly enhanced the cytotoxicities against the A-549 human lung and the MCF-7 human beast solid tumor cell lines. One known monotetrahydrofuran acetogenin, gigantetronenin, not described previously from this plant, was also found.

Intercellular contacts and the organization of actin filaments in cultured epithelial FL cells are altered by growth on type I collagen and treatment with 12-O-tetradecanoylphorbol-13-acetate through the modulation of interactions between cells and the substratum.

We have investigated the effects of various types of collagen and a tumor-promoting phorbol ester on intercellular contacts and the organization of actin in human amnion epithelial FL cells and mouse fibroblast 3T3-A31 cells. Our purpose was to investigate how modulation of interactions between cells and the substratum leads to alterations in intercellular contacts and organization of actin filaments. When cells were cultured on dishes coated with a solution containing type I collagen, but not type IV, changes were induced in the morphology of FL cells and their intercellular contacts. Type I collagen also caused changes in the organization of their actin filaments, although no such effects were observed with 3T3-A31 cells. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA) caused morphological changes, dissociation of groups of cells, and reorganization of actin filaments in cultures of FL and 3T3-A31 cells. It also disrupted the sites of adhesion of FL cells to the substratum. Both type I collagen and TPA rapidly induced spreading of FL cells in the absence of serum. However, cis-hydroxyproline, known to inhibit secretion of collagen, did not suppress the TPA-induced dissociation of groups of FL cells. These results suggest that the interactions with type I collagen of epithelial FL cells, but not of fibroblastic 3T3-A31 cells, tend to disorganize cellular morphology, intercellular contacts, and actin filaments in ways similar to, but not directly related to, the effects of TPA.

Possible involvement of reorganization of actin filaments, induced by tumor-promoting phorbol esters, in changes in colony shape and enhancement of proliferation of cultured epithelial cells.

Tumor promoters are known to induce reorganization of actin, morphological changes and enhancement of proliferation of epidermal cells in vivo. In this study, we have examined the effects of tumor promoters on these events to clarify the role played by the organization of actin filaments in the regulation of the shape and growth of colonies of epithelial cells in culture. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a change in the shape of colonies of FL and Madin-Darby canine kidney (MDCK) cells within 6 hr. Changes in the shape of colonies were consistent with the morphological change of individual cells and the dissociation of groups of cells in the colonies. Addition of TPA also caused reorganization of actin filaments after 2 hr, and it caused enhancement of proliferation of FL and MDCK cells after 48 hr but did not cause any such changes in KB cells. However, the binding affinities of 4 beta-phorbol 12,13-dibutyrate (PDBu) to FL and MDCK cells were similar to that of PDBu to KB cells. Related tumor promoters such as phorbol 12,13 didecanoate (PDD) and mezerein caused effects similar to those caused by TPA. In contrast, nontumor promoting phorbol esters, such as 4 alpha-PDD and phorbol, had no effect. Cyclic AMP blocked the TPA-induced changes in FL and MDCK cells. These results suggest that TPA-induced reorganization of actin filaments which can be inhibited by cyclic AMP results in changes in the shape of colonies and enhancement of proliferation.