Antineoplastic Agents. 380. Isolation and X-ray Crystal Structure Determination of Isoaaptamine from the Republic of Singapore Hymeniacidon sp. and Conversion to the Phosphate Prodrug Hystatin 1

Abstract

By use of bioassay (murine P388 lymphocytic leukemia cell line) guided isolation procedures, extracts of the Republic of Singapore marine sponge Hymeniacidon sp. were found to contain demethyloxyaaptamine (1) and aaptamine (3) as prominent cancer cell growth inhibitory constituents accompanied by the trace, albeit more active, component isoaaptamine (4). The isolation, X-ray structure elucidation, and antineoplastic and antimicrobial activities of isoaaptamine (4) have been summarized. Because of instability, isoaaptamine (4) was converted to a stable sodium phosphate prodrug designated hystatin 1 (7).

Aaptamine and related products. Their isolation, chemical syntheses, and biological activity

“…Therefore, Pettit et al 42 directed their attention at the preparation of stable prodrugs that would retain the biological activity of isoaaptamine. …”

“…132 The prodrug Hystatin 1 (163) a stable derivative prepared to overcome slow degradation of isoaaptamine (2), retained some of the P388 cytotoxic activity of the parent compound, as shown in Table 9. 42 These aaptamine derivatives were also examined for potential effects on tubulin assembly. 126 Except for isoaaptamine (2) and 9-demethylaaptamine (3), which weakly inhibited the extent of tubulin assembly (IC 50 ¼31 mM and 37 mM, respectively), no significant activity was observed among the aaptaminoids at the highest concentration evaluated (40 mM).…”

Regioselective intramolecular electrophilic substitution reactions involving π-deficient pyridine substrates: a new entry to pyridoquinazolines and benzo[h][1,6]naphthyridines

“…The organic layer was washed with brine, dried over Na 2 SO 4 and then concentrated in vacuo. The crude mixture was then subjected to column chromatography (100-200 silica gel) using ethyl acetate:hexane (95: 5 The solution of 2-bromoaniline (2.0 g, 11.62 mmol), bis[pinaclolato]diboron (3.24 g, 12.78 mmol), potassium acetate (1.7 g, 17.43 mmol), and tricyclohexyl phosphine (0.39 g, 1.39 mmol) in dry dioxane (15 ml) was purged with nitrogen for 15 min followed by the addition of tris[dibenzylideneacetone]dipalladium(0) (0.53 g, 0.58 mmol). The reaction mixture was heated at 80 C for 16 h, filtered through Celite, washed with ethyl acetate and concentrated to get the product, which was used without further purification.…”

“…They are associated with a wide spectrum of biological activities ranging from anticancer, 2 antiherpes, 3 anti-HIV-1, 4 antimicrobial, 5 adrenoceptor blocking 6 to sortase A, 7 HIV-1 integrase inhibitors, 8 and Spleen Tyrosine Kinase 9 inhibitory activities.…”

An efficient synthesis of novel benzo[b]pyrido[3′,2′:4,5]thieno[2,3-e][1,6]naphthy-ridine-8-ones

“…Among them, 1,6-naphthyridine and their fused analogs are an important pharmacophore present in many natural [2] and designed synthetic products of therapeutic value. They are associated with a wide spectrum of biological effects such as anticancer [3], anti-HIV-1 [4], antimicrobial [5] and cytotoxic activities [6]. Therefore, the synthesis of 1,6-naphthyridine derivatives has aroused great interest in organic and medicinal chemistry communities [7][8][9][10][11].…”