Biomedical subjects

F Q Alali

Publications and source records attributed to F Q Alali.

12 recordsLinked to original sources

PubMed1999

Two bioactive mono-tetrahydrofuran acetogenins, annoglacins A and B, from Annona glabra.

Two new bioactive mono-THF Annonaceous acetogenins, annoglacins A and B, have been isolated from the fractionated ethanolic extracts of the leaves of Annona glabra, directing the fractionation with the brine shrimp lethality test (BST). Their structures were elucidated based on spectroscopic and chemical methods and the absolute stereochemistries were determined by the advanced Mosher ester method. Annoglacins A and B were selectively 1000 and 10,000 times, respectively, more potent than adriamycin against the human breast carcinoma (MCF-7) and pancreatic carcinoma (PACA-2) cell lines in our panel of six human solid tumor cell lines.

Animals↗

PubMed1999

Goniotriocin and (2,4-cis- and -trans)-xylomaticinones, bioactive annonaceous acetogenins from Goniothalamus giganteus.

Goniotricin (1) and a mixture of (2,4-cis and -trans)-xylomaticinones (2), new bioactive annonaceous acetogenins, were isolated from the bark of Goniothalamus giganteus (Annonaceae) by activity-directed fractionation using the brine shrimp lethality test. Compound 1 is the first nonadjacent ring-hydroxylated bis-tetrahydrofuran (THF) acetogenin to be reported. Compound 2 is the cis- and trans-ketolactone mixture of xylomaticin, a known compound whose absolute stereochemistry has not been previously determined. The absolute stereochemistry of 2 was determined by the advanced Mosher's ester method. Both 1 and 2 showed significant and selective cytotoxicities among the six tumor cell lines in our seven-day MTT human solid tumor panel. In the yellow fever mosquito larvae microtiter assay, 1 was quite active, with an ED50 value of 3. 5 microg/mL.

Animals↗

PubMed1999

Annonaceous acetogenins: recent progress.

The Annonaceous acetogenins are promising new antitumor and pesticidal agents that are found only in the plant family Annonaceae. Chemically, they are derivatives of long-chain fatty acids. Biologically, they exhibit their potent bioactivities through depletion of ATP levels via inhibiting complex I of mitochondria and inhibiting the NADH oxidase of plasma membranes of tumor cells. Thus, they thwart ATP-driven resistance mechanisms. This review presents the progress made in the chemistry, biology, and development of these compounds since December 1995.

Animals↗

PubMed1998

Mono-THF ring annonaceous acetogenins from Annona squamosa.

Continuing work on the bark of Annona squamosa Rich. (Annonaceae), directed by the brine shrimp lethality test (BST), has resulted in the isolation of three new Annonaceous acetogenins, 4-deoxyannoreticuin, cis-4-deoxyannoreticuin, and (2,4-cis and trans)-squamoxinone. The first two are additional examples of acetogenins isolated from this plant species which contain the unusual feature of an oxygen functionality at the C-9 position. They have a hydroxylated mono-THF ring with respective threo/trans/threo and threo/cis/threo relative stereochemistries. The latter compound is a ketolactone mixture which has the same relative stereochemistry around the THF ring and the same spatial relationship between the THF ring and the hydroxyl group along the aliphatic chain as 4-deoxyannoreticuin, but is two methylene units longer. Additionally, the isolated hydroxyl group is at C-11, while the THF ring starts at C-17, instead of at C-9 and C-15, respectively, as for the first two compounds. All three compounds showed moderate, but significant, cytotoxicities against a panel of six human tumor cell lines with (2,4 cis and trans)-squamoxinone showing promising selectivity against the pancreatic cell line (PACA-2).

4-Butyrolactone↗

PubMed1998

Mono-tetrahydrofuran acetogenins from Goniothalamus giganteus.

Goniotetracin and a mixture of (2,4-cis and trans)-gonioneninone, new, bioactive, mono-tetrahydrofuran (THF) gamma-lactone and ketolactone acetogenins, were isolated from the bark of Goniothalamus giganteus (Annonaceae) by activity-directed fractionation using the brine shrimp lethality test (BST). The structures were elucidated based on spectroscopic and chemical methods. Their absolute stereochemistries were determined by the advanced Mosher ester method. Both showed selective and significant cytotoxicities, comparable to the potency of adriamycin, to the human pancreatic tumour cell line (PACA-2), while goniotetracin and goniothalamicin were comparable to the activity of rotenone against yellow fever mosquito larvae.

4-Butyrolactone↗

PubMed1998

Annojahnin from Annona jahnii: a possible precursor of mono-tetrahydrofuran acetogenins.

A new cytotoxic Annonaceous acetogenin, annojahnin (1), was isolated from the twigs of Annona jahnii (Annonaceae) by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C-37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings, bearing a keto group at C-10, and possessing a double bond located two methylenes away from a vicinal diol. The structure and absolute configuration of 1 were elucidated by 1H and 13C NMR, COSY, and single-relayed COSY and from chemical derivatives. 4-Deoxy-18/21-trans-annomontacin 10-one (4) and 4-deoxy-18/21-cis-annomontacin-10-one (5), two semisynthetic mono-THF acetogenins, were prepared from 1 by reactions that mimic the biogenetic pathways. These acetogenins showed selective cytotoxicities, comparable or superior to adriamycin, among six human solid tumor cell lines. Reduction of the 10-keto of 1, to the racemic 10-OH derivative (3), retained the bioactivities as did the conversion of 1 to 4 and 5.

4-Butyrolactone↗

PubMed1998

Three new bioactive bis-adjacent THF-ring acetogenins from the bark of Annona squamosa.

Continuing work on the bioactivity-directed fractionation of the bark of Annona squamosa has resulted in the discovery of three new Annonaceous acetogenins, (2,4-cis and trans)-squamolinone (1), (2,4-cis and trans)-9-oxoasimicinone (2), and bullacin B (3). Compounds 1-3 are all adjacent bis-THF ring acetogenins with 2 representing the first bis-ring acetogenin to contain a carbonyl along its aliphatic chain. Compound 3 was selectively cytotoxic in a panel of six human tumor cell lines with a potency of nearly a million times that of adriamycin against the MCF-7 (human breast adenocarcinoma) cell line.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Glabracins A and B, two new acetogenins from Annona glabra.

Two new bioactive bis-THF Annonaceous acetogenins, glabracins A (1) and B (2), and two previously known acetogenins, javoricin (3) and bullatanocin (4), have been isolated from the leaves of Annona glabra by activity-directed fractionation using the brine shrimp lethality test (BST). The structures of 1 and 2 were elucidated based on spectroscopic and chemical methods, and the absolute stereochemistries were partially determined by the advanced Mosher ester method. 1 and 2 showed selective cytotoxicities to certain human tumor cell lines, and 1 was significantly more potent although 1 and 2 differ only in the stereochemistry of their vicinal diols at C-23/24.

Animals↗

PubMed1998

New bioactive triterpenoids from Melia volkensii.

Bioactivity-directed fractionation of the root bark of Melia volkensii resulted in the isolation of two new natural products, meliavolkinin (1) and melianin C (3), together with two known compounds, 1,3-diacetylvilasinin (2) and melianin B (4). Jones oxidation of 4 gave compounds 3, 23,24-diketomelianin B (5), and 16,23,24-triketomelianin B (6). The structures of the new compounds were elucidated by spectral and chemical data. Compounds 1-6 all showed marginal cytotoxicities against certain human tumor cell lines, while 5 showed selective cytotoxicities for the human prostate (PC-3) and pancreatic (PACA-2) cell lines with potencies comparable to those of adriamycin.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Glacins A and B: two novel bioactive mono-tetrahydrofuran acetogenins from Annona glabra.

Two new bioactive mono-THF Annonaceous acetogenins, glacins A (1) and B (2), have been isolated, from the fractionated ethanolic extracts of the leaves of Annona glabra, directing the fractionation with the brine shrimp lethality test (BST). The structures of 1 and 2 were elucidated on the basis of spectroscopic and chemical methods, and the absolute stereochemistries were solved by preparing their respective per-Mosher ester derivatives. 1 and 2 showed potent and selective in vitro cytotoxicities among several human solid tumor cell lines.

4-Butyrolactone↗

PubMed1998

Annonaceous acetogenins as natural pesticides: potent toxicity against insecticide-susceptible and -resistant German cockroaches (Dictyoptera: Blattellidae).

Six compounds, representing the mono-tetrahydrofuran (THF) (gigantetrocin A, annomontacin), adjacent bis-THF (asimicin, parviflorin), and nonadjacent bis-THF (sylvaticin, bullatalicin) classes of annonaceous acetogenins, were compared with technical grades of synthetic amidinohydrazone (hydramethylnon), carbamate (propoxur, bendiocarb), organophosphate (chlorpyrifos), and pyrethroid (cypermethrin) insecticides to determine their dietary toxicities to insecticide-resistant and insecticide-susceptible strains of the German cockroach, Blattella germanica (L.). Differential susceptibility occurred among B. germanica nymphs of both strains to this variety of the acetogenins and the 5 conventional synthetic insecticides. The speed of kill (LT50) values against insecticide-susceptible and insecticide-resistant 2nd and 5th instars permitted ranking of all 11 compounds. The adjacent bis-THF acetogenins showed the highest potency among the 3 acetogenin classes. The acetogenins caused high percentages of mortality and delays in development of the 5th instars of both strains. Insecticide-susceptible nymphal development was mainly affected by gigantetrocin A and annomontacin, whereas insecticide-resistant nymphal development was mainly affected by gigantetrocin A and bullatalicin. Most tested acetogenins performed better than the conventional insecticides against both stages of both strains. No growth regulation effects were caused by any of the compounds tested. Low resistance ratios were obtained for most compounds (except chlorpyrifos). Low resistance ratios values for 2nd instars ranged from 0.9 to 2.2 with the natural acetogenins and from 1.0 to 3.8 with the synthetic compounds; the 5th instars ranged from 0.2 to 3.9 with the natural acetogenins and from 0.6 to 8.0 with the synthetic compounds. Insecticidal properties and characteristics of acetogenins and the possible use of acetogenins in baits for cockroach control are discussed.

Animals↗

PubMed1997

(2,4-cis and trans)-gigantecinone and 4-deoxygigantecin, bioactive nonadjacent bis-tetrahydrofuran annonaceous acetogenins, from Goniothalamus giganteus.

Two new acetogenins, (2,4-cis and trans)-gigantecinone (1), isolated as a mixture, and 4-deoxygigantecin (2), a known acetogenin whose absolute stereochemistry has not been determined previously, were isolated using activity-directed fractionation, from the bark of Goniothalamus giganteus. A key step in solving their absolute stereochemistries was the preparation of 1,4-diol formaldehyde acetal derivatives (1b and 2a). Using the advanced Mosher ester method and circular dichroism, the absolute stereochemistries of 1 and 2 were revealed and were found to be the same as that of gigantecin (3), which supports a common biogenetic origin. Both 1 and 1b showed potent and selective cytotoxicities against the PC-3 human prostate adenocarcinoma cell line. Against yellow fever mosquito larvae, 1 and 2 were more potent than rotenone in pesticidal activity. Longimicin C and a mixture of (2,4-cis and trans)-isoannonacin were also isolated for the first time from this species.

Acetylation↗