Sarfraz Ahmad Nawaz

Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus.

Several secondary metabolites, artemetin (1), casticin (2), 3,3′‐dihydroxy‐5,6,7,4′‐tetramethoxy flavon (3), penduletin (4), methyl 4‐hydroxybenzoate (5), p‐hydroxybenzoic acid (6), methyl 3,4‐dihydroxybenzoate (7), 5‐hydroxy‐2‐methoxybenzoic acid (8), vanillic acid (9) and 3,4‐dihydroxybenzoic acid (10) were isolated from a folkloric medicinal plant, Vitex agnus‐castus. The structures of compounds 1–10 were identified with the help of spectroscopic techniques. Compounds 3–10 were isolated for the first time from this plant. These compounds were screened for their antiinflammatory and lipoxygenase inhibitory activities. Compounds 6, 7 and 10 were found to have significant antiinflammatory activity in a cell‐based contemporary assay, whereas compounds 1 and 2 exhibited a potent lipoxygenase inhibition. Copyright

New pregnane-type steroidal alkaloids from Sarcococca saligna and their cholinesterase inhibitory activity

Five new steroidal alkaloids, 5,14-dehydro-N(a)-demethylsaracodine [3beta-N(a)-methyl-20S-N(b)-acetyl-N(b)-methylamino-pregn-5,14-diene] (1), 14-dehydro-N(a)-demethylsaracodine [3beta-N(a)-methyl-20S-N(b)-acetyl-N(b)-methylamino-5alpha-pregn-14-ene] (2), 16-dehydrosarcorine [(20S)-20-(N,N-dimethylamino)-3beta-(N(a)-acetylamido)-5alpha-pregn-16-ene] (3), 2,3-dehydrosarsalignone [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-pregn-2,5-diene-4-one] (4), and 14,15-dehydrosarcovagine-D [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-5alpha-pregn-2,14-diene-4-one] (5), were isolated from the ethanolic extract of Sarcococca saligna, along with two known bases, sarcovagenine-C (6) and salignarine-C (7). Their structures were elucidated on the basis of spectroscopic methods. All seven compounds were found to possess cholinesterase inhibitory potential in a concentration-dependent manner with the IC50 values ranging from 12.5 to 200 microM against acetylcholinesterase and from 1.25 to 32.2 microM against butyrylcholinesterase.

Muscarinic, Ca++ antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia

Ginger rhizome (Zingiber officinale) has been used for centuries to treat dementia in South Asia. This study was undertaken to possibly justify its use. A 70% aqueous/methanolic extract of dried ginger (Zo.Cr) was used. Zo.Cr tested positive for the presence of terpenoids, flavonoids, secondary amines, phenols, alkaloids and saponins. When tested on isolated rat stomach fundus, Zo.Cr showed a spasmogenic effect (0.03–5.00 mg mL−1); it relaxed the tissue at concentrations ≥5 mg mL−1. The stimulant effect was resistant to blockade by hexamethonium and methysergide, but sensitive to atropine, indicating activity via muscarinic receptors. In atropinized (0.1 μM) preparations, Zo.Cr (0.3–3.0 mg mL−1) relaxed high K+ (80 mm)‐induced contractions, indicating Ca++ antagonism in addition to the muscarinic effect. This possible Ca++ antagonist activity was investigated in Ca++‐free conditions, with the inhibitory effect of the extract tested against contractions induced by externally administered Ca++. Zo.Cr (0.1–0.3 mg mL−1), similar to verapamil (0.03–0.10 μm), shifted the contractions induced by externally administered Ca++ to the right, thus suggesting an inhibitory interaction between Zo.Cr and voltage‐operated Ca++ channels. Zo.Cr (0.1–3.0 μg mL−1) also potentiated acetylcholine peak responses in stomach fundus, similar to physostigmine, a cholinesterase inhibitor. Zo.Cr, in an in‐vitro assay, showed specific inhibition of butyrylcholinesterase (BuChE) rather than acetylcholinesterase enzyme. Different pure compounds of ginger also showed spasmolytic activity in stomach fundus, with 6‐gingerol being the most potent. 6‐Gingerol also showed a specific anti‐BuChE effect. This study shows a unique combination of muscarinic, possible Ca++ antagonist and BuChE inhibitory activities of dried ginger, indicating its benefit in dementia, including Alzheimers disease.

Synthesis and inhibitory potential towards acetylcholinesterase, butyrylcholinesterase and lipoxygenase of some variably substituted chalcones

A series of variably substituted chalcones were synthesized by condensation of substituted acetophenones with mono-, di- or trisubstituded benzaldehydes. It was observed that some of these compounds have the potential to inhibit acetylcholinesterase, whereas others show activity against butyrylcholinesterase, depending on the substitution pattern at the two aromatic rings of these chalcones. Similarly, lipoxygenase was inhibited by two of these compounds. It has been observed that inhibition of the three enzymes was concentration dependent with the IC50 values ranging from 28.2–134.5 μM against acetylcholinesterase, 16.0–23.1 μM against butyrylcholinesterase and 57.6–71.7 μM against lipoxygenase, respectively.

Microbial transformation of prednisone

The microbial transformation of prednisone (17α,21-dihydroxy-pregna-1,4-diene-3,11,20-trione) (1) by Cunninghamella elegans afforded two metabolites, 17α,21-dihydroxy-5α-pregn-1-ene-3,11,20-trione (2) and 17α,20S,21-trihydroxy-5α-pregn-1-ene-3,11-dione (3), while the fermentation of 1 with Fusarium lini, Rhizopus stolonifer and Curvularia lunata afforded a metabolite 1,4-pregnadiene-17α,20S,21-triol-3,11-dione (4). Compound 3 was found to be a new metabolite. Their structures were elucidated on the basis of spectroscopic techniques. Compound 3 showed inhibitory activity against lipoxygenase enzyme.

Lipoxygenase inhibitory constituents from Indigofera oblongifolia.

Indigin, alkylated xanthene (1) and indigoferic acid (2) have been isolated from the chloroform soluble fraction ofIndigofera oblongifolia, along with β-sitosterol (3) and 3-hydroxybenzoic acid (4), which are reported for the first time from this species. Their structures were determined through spectroscopic techniques. Both the new compounds1 and2 showed significant activity against enzyme lipoxygenase, while2 further showed moderate inhibition against BChE.

New Steroidal Alkaloids From Sarcococca Saligna

Two new steroidal alkaloids, salonine-A [(20S)-20-(N,N-dimethylamino)-3β-(tigloylamino)-5α-pregn-14-en-2β,4β-diol] (1), and salonine-B [(20S)-20-(N,N-dimethylamino)-3β-methoxy-pregn-5,16-diene] (2), were isolated from the MeOH extract of Sarcococca saligna, along with a known base, alkaloid-C (3). Their structures were elucidated on the basis of spectroscopic methods. All three compounds were found to be cholinesterase inhibitors.

Butyrylcholinesterase inhibitory guaianolides fromAmberboa ramosa

Phytochemical investigation of the whole plant of Amberboa ramosa led to the isolation of six sesquiterpene lactones which could be identified as 8α-hydroxy-11β-methyl-1αH, 5αH, 6βH, 7αH, 11αH-guai-10(14), 4(15)-dien-6, 12-olide(1), 3β 8α-dihydroxy-11α-methyl-1αH, 5αH, 6βH, 7αH, 11βH-guai-10(14), 4 (15)-dien-6, 12-olide (2), 3β, 4α, 8α-trihydroxy-4β-(hydroxymethyl)-1αH, 5αH, 6βH, 7αH-guai-10(14), 11(13)-dien-6, 12-olide (3), 3β, 4α, 8α-trihydroxy-4β-(chloromethyl)-1αH, 5αH, 6βH, 7αH-guai-10(14),11(13)-dien-6, 12-olide(4), 3β, 4α, dihydroxy-4β-(hydroxymethyl)-1αH, 5αH, 6βH, 7αH-guai-10(14),11(13)-dien-6, 12-olide(5), 3β, 4α-dihydroxy-4β-(chloromethyl)-8α-(4-hydroxymethacrylate)-1αH, 5αH, 6βH, 7αH-guai-10(14),11 (13)-dien-6,12-olide (6) by spectroscopic methods. All of them showed inhibitory potential against butyrylcholinesterase.

Lipoxygenase inhibiting ethyl substituted glycoside from Symplocos racemosa.

Phytochemical investigation of Symplocos racemosa resulted in the isolation of a new ethyl substituted glycoside, 1-ethyl brachiose-3′-acetate (1) along with four known compounds ketochaulmoogric acid (2), nonaeicosanol (3), triacontyl palmitate (4) and methyl triacontanoate (5). The substitution of ethyl group on 1 was natural because during the course of extraction and purification ethanol was not used. The structural elucidation of the isolated compounds was based primarily on 1D- and 2D-NMR analysis, including COSY, HMQC, and HMBC correlations. The glycoside 1 and triacontyl palmitate (4) displayed the inhibitory potential against lipoxygenase and urease enzyme, respectively.

Phenolic constituents from Perovskia atriplicifolia

Perovskoate, an isorinic acid derivative (1) and perovskoside, the catechol derivative (2) have been isolated from the ethyl acetate soluble fraction of the whole plant of Perovskia atriplicifolia and assigned the structure 3(7-hydroxyphenyl)-2-hydroxy propanoic acid; (R)-form, 2-O-(6′,7′-dihydroxy-E-cinnamoyl) (1) and 2-methoxy-4-(undecyl-4′-O-β-D-glucopyranosyl) phenol (2). In addition, caffeic acid (3) and ferulic acid (4) have been reported for the first time from this species. The structures of these compounds were assigned on the basis of 1D and 2D NMR techniques. The compound 1 showed significant inhibitory activity against lipoxygenase and weak to moderate activity against cholinesterases.