Ashraf Taha Khalil

Cytotoxic Benzophenanthridine and Benzylisoquinoline Alkaloids from Argemone mexicana

Abstract Fractionation of the chloroform extract from the aerial part of Argemone mexicana led to the isolation of two benzophenanthridine-type alkaloids, N-demethyloxysanguinarine and pancorine; three benzylisoquinoline-type alkaloids, (+)-1,2,3,4-tetrahydro-1-(2-hydroxymethyl- 3,4-dimethoxyphenylmethyl)-6,7-methylenedioxyisoquinoline, (+)-higenamine and (+)-reticuline. Among them, N-demethyloxysanguinarine is a new compound, and (+)-1,2,3,4- tetrahydro-1-(2-hydroxymethyl-3,4-dimethoxyphenylmethyl)-6,7-methylenedioxy-isoquinoline was isolated form a natural source for the first time, to which was assigned a trivial name, (+)-argenaxine. In addition, six known non-alkaloidal compounds were also isolated and identified. All compounds were characterized on the basis of their spectral data and chemical evidences. Some isolated alkaloids from this species were evaluated for their cytotoxicity to human nasopharyngeal carcinoma (HONE-1) and human gastric cancer (NUGC) cell lines. Chelerythrine was found to exhibit significant activity against NUGC cell line, while angoline inhibited both types. (+)-Argenaxine showed moderate activity against the NUGC cell line.

Frajunolides E-K, briarane diterpenes from Junceella fragilis.

Chemical investigation of the gorgonian octocoral Junceella fragilis, collected in Taiwan, resulted in the isolation of seven new briarane-type diterpenes, frajunolides E-K (1-7), in addition to 14 known briaranes, praelolide, junceellin, junceellolides A-E, and K, 11a,20a-epoxy-4-deacetoxyjunceelolide D, umbraculolide A, junceellonoid A, and juncins Y, Z, and ZI, as well as ergosterol peroxide. The structures of 1-7 were determined by analysis of HRESIMS and 2D NMR spectroscopic data. Cytotoxicity and in vitro anti-inflammatory activities of compounds 1-7 were also evaluated.

Benzylamides from Salvadora persica

A phytochemical investigation of stems fromSalvadora persica resulted in the first isolation of four benzylamides from a natural source. The isolated compounds were identified as butanediamide,N1,N4-bis(phenylmethyl)-2(S)-hydroxy-butanediamide (1),N-benzyl-2-phenylacetamide (2),N-benzylbenzamide (3) and benzlurea (4). The structure elucidation was accomplished using spectroscopic methods, especially 2D NMR and HREIMS. Compound2 revealed a significant inhibitory effect on human collagen-induced platelet aggregation, and a moderate antibacterial activity againstEscherichia coli.

Pregnane glycosides from Caralluma retrospiciens

Two pregnane ester glycosides were isolated and identified from the alcohol extract of the aerial parts of Caralluma retrospiciens. Their structures were established as 12 beta-benzoyloxy-20-isovaleroyloxy-8 beta,14 beta-dihydroxypregnane-3-O -[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl -(1-->4)-beta-D-(3-O-methyl-6-deoxy)-galactopyranoside] (caretroside A) and the bioside 12 beta-benzoyloxy-8 beta,14 beta-dihydroxypregn-20-one-3-O-[beta -D-oleandropyranosyl-(1-->4)-beta-D-cymaropyranoside]. They were characterized through physical and chemical methods in addition to standard spectroscopic techniques especially 2D NMR (COSY, HMQC and HMBC). This is the first report of the isolation of these compounds from a natural source.

Cembrane diterpenoids from the taiwanese soft coral Sarcophyton stolidotum.

Investigation of an EtOAc-soluble extract of the soft coral Sarcophyton stolidotum resulted in the isolation of seven new 14-membered carbocyclic cembranes, sarcostolides A-G (1-7), together with two known cembrane diterpenes, isosarcophytoxide and isosarcophine. The structural elucidation of these metabolites was determined on the basis of spectroscopic analyses, particularly 2D NMR techniques. Sarcostolide E (5) exhibited weak to moderate cytotoxic activity against human WiDr and Daoy tumor cell lines. A biogenetic pathway and relationship for compounds 1-7 was also proposed.

Sinuladiterpenes A-F, new cembrane diterpenes from Sinularia flexibilis.

Chromatographic investigation of the octocoral Sinularia flexibilis afforded six new cembrane diterpenes, sinuladiterpenes A–F (1–6, resp.), in addition to four known cembranolides, 11‐episinulariolide acetate, 11‐dehydrosinulariolide, 11‐episinulariolide, and sinulariolide. Their structures were elucidated by spectroscopic analysis, especially 2D‐NMR and HR‐ESI‐MS. Compound 2 exhibited significant in vitro cytotoxic activity against human colon adenocarcinoma (WiDr) cell line.

New bioactive clerodane diterpenoids from the roots of Casearia membranacea.

Bioassay‐guided fractionation of the acetone extract of the roots of Casearia membranacea furnished three new clerodane diterpenes, caseamembrins S–U (1–3) and the known caseamembrin Q (4). Their structures were established by extensive spectroscopic analyses, especially 2D‐NMR. Compounds 1–4 were tested against human tumor cells, including HeLa (cervical epitheloid carcinoma), DLD‐1 (colon carcinoma), Daoy (medulloblastoma), and KB (oral epidermoid carcinoma) cell lines. Caseamembrin T (2) exhibited the most potent activity against Daoy cells (ED50=10 ng/ml), superior to that of the standard drug mitomycin.

Chemical Constituents from the Hydrangea chinensis

Two quinazolone alkaloids, (+)-febrifugine (1) and isofebrifugine (2), along with three coumarin derivatives, 6-hydroxy coumarin (3), skimmin (5), and umbelliferone-7-O-α-L-rhamnopyranosyl(1→4)-β-D-glucopyranoside (6), were isolated from the roots ofHydrangea chinensis. Compound6 is a new compound. In addition, umbelliferone (4), linoleic acid (7), two steroidal glycosides (8, 9), three furfural derivatives (10–12), and butyl-β-D-fructofuranoside (13) were isolated from the leaves of the same plant. The structures of all isolates were elucidated by spectral methods.

Bioactive Marine Prostanoids from Octocoral Clavularia viridis

Chemical investigation of the nonpolar extract of soft coral Clavularia viridis resulted in isolation of five new prostanoids, designated as claviridic acids A–E (1–5, resp.), in addition to the known clavulones I–III. Their structures were determined on the basis of spectroscopic techniques, especially HR‐ESI‐MS, CD, and 2D‐NMR experiments. The isolated marine prostanoids exhibited potent inhibitory effect on PHA‐induced proliferation of peripheral blood mononuclear cells (PBMC), as well as significant cytotoxic activity against human gastric cancer cells (AGS).

Cespihypotins Q−V, Verticillene Diterpenoids from Cespitularia hypotentaculata

Chemical investigation of the soft coral Cespitularia hypotentaculata resulted in the isolation of six new diterpenes, cespihypotins Q-V. The new metabolites comprised five verticillane-type diterpenes and one nor-verticillane derivative. Their structures were determined through detailed spectroscopic analyses, especially HRESIMS and 2D NMR techniques. The relative configuration was deduced by interpretation of NOESY spectra. Cespihypotin T exhibited significant cytotoxic activity against human Daoy and WiDr tumor cell lines.