Nawaz SA

References (28)

Title : Cation-Pi and Pi-Pi stacking interactions allow selective inhibition of butyrylcholinesterase by modified quinine and cinchonidine alkaloids - Nawaz_2011_Biochem.Biophys.Res.Commun_404_935
Author(s) : Nawaz SA , Ayaz M , Brandt W , Wessjohann LA , Westermann B
Ref : Biochemical & Biophysical Research Communications , 404 :935 , 2011
Abstract : Scaffold varied quaternized quinine and cinchonidine alkaloid derivatives were evaluated for their selective butyrylcholinesterase (BChE) inhibitory potential. K(i) values were between 0.4-260.5microM (non-competitive inhibition) while corresponding K(i)values to acetylcholinesterase (AChE) ranged from 7.0-400microM exhibiting a 250-fold selectivity for BChE. Docking arrangements (GOLD, PLANT) revealed that the extended aromatic moieties and the quaternized nitrogen of the inhibitors were responsible for specific Pi-Pi stacking and Pi-cation interactions with the choline binding site and the peripheral anionic site of BChE's active site.
ESTHER : Nawaz_2011_Biochem.Biophys.Res.Commun_404_935
PubMedSearch : Nawaz_2011_Biochem.Biophys.Res.Commun_404_935
PubMedID: 21185266

Title : Assessment of enzyme inhibitory and antioxidant activities of lignans from Taxus baccata L - Kucukboyaci_2010_Z.Naturforsch.C_65_187
Author(s) : Kucukboyaci N , Orhan I , Sener B , Nawaz SA , Choudhary MI
Ref : Z Naturforsch C , 65 :187 , 2010
Abstract : Phytochemical investigations of Taxus baccata L. by successive chromatographic methods resulted in the isolation of the lignans lariciresinol (1), taxiresinol (2), 3'-demethylisolariciresinol-9'-hydroxyisopropylether (3), isolariciresinol (4), and 3-demethylisolariciresinol (5) as well as taxoids. Compounds 1-5 were evaluated for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and lipoxygenase (LOX) inhibitory activities, which play a role in the pathogenesis of Alzheimer's disease (AD), by in vitro spectrophotometric methods, while they were also screened for their antioxidant capacity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferrous ion-chelating effect, and ferric-reducing antioxidant power (FRAP) at 125, 250, 500, and 1000 microg ml(-1). All compounds exhibited a moderate inhibition against both BChE and LOX, whereas they were inactive towards AChE. The compounds displayed a great scavenging activity against DPPH especially at 500 and 1000 microg ml(-1). Besides, they were found to exert noteworthy reducing antioxidant power on ferric ions. In particular, the FRAP of compounds 2 (3.552 +/- 0.02), 4 (3.021 +/- 0.71), and 5 (3.533 +/- 0.01) were as high as that of the reference chlorogenic acid (3.618 +/- 0.01) at 1000 microg ml(-1). None of the compounds exhibited chelating ability against ferrous ions.
ESTHER : Kucukboyaci_2010_Z.Naturforsch.C_65_187
PubMedSearch : Kucukboyaci_2010_Z.Naturforsch.C_65_187
PubMedID: 20469636

Title : Structural insight into the inhibition of acetylcholinesterase by 2,3,4, 5-tetrahydro-1, 5-benzothiazepines - Nawaz_2008_J.Enzyme.Inhib.Med.Chem_23_206
Author(s) : Nawaz SA , Umbreen S , Kahlid A , Ansari FL , Choudhary MI
Ref : J Enzyme Inhib Med Chem , 23 :206 , 2008
Abstract : Benzothiazepines 1-3 inhibited acetylcholinesterase (AChE; EC 3.1.1.7) enzyme in a concentration-dependent fashion with IC(50) values of 1.0 +/- 0.002, 1.2 +/- 0.005 and 1.3 +/- 0.001 microM, respectively. By using linear-regression equations, Lineweaver-Burk, Dixon plots and their secondary replots were constructed which indicated that compounds 1-3 are non-competitive inhibitors of AChE with K(i) values of 0.8 +/- 0.04, 1.1 +/- 0.002, and 1.5 +/- 0.001 microM, respectively. Molecular docking studies revealed that all the compounds are completely buried inside the aromatic gorge of AChE, extending deep into the gorge of AChE. A comparison of the docking results of compounds 1-3 displayed that these compounds generally adopt the same binding mode in the active site of AChE. The superposition of the docked structures demonstrated that the non-flexible benzothiazepine always penetrate into the aromatic gorge through the six-membered ring A, which allowed the ligands to interact simultaneously with more than one subsites of the active center of AChE. The higher AChE inhibitory potential of compounds 1-3 was found to be the cumulative effect of hydrophobic contacts and pi-pi interactions between the ligands and AChE. The relatively high affinity of benzothiazepine 1 with AChE was found to be due to additional hydrogen bond in benzothiazepine 1-AChE complex. The results indicated that substitution of halogen and methyl groups by hydrogen at aromatic ring of the benzothiazepine decreased the affinity of these molecules towards enzyme that may be due to the polar non-polar repulsions of these moieties with the amino acid residues in the active site of AChE. The observed binding modes of benzothiazepines 1-3 in the active site of AChE explain the affinities of benzothiazepines and provide a rational basis for the structure-based drug design of benzothiazepines with improved pharmacological properties.
ESTHER : Nawaz_2008_J.Enzyme.Inhib.Med.Chem_23_206
PubMedSearch : Nawaz_2008_J.Enzyme.Inhib.Med.Chem_23_206
PubMedID: 18343905

Title : Isolation and enzyme-inhibition studies of the chemical constituents from Ajuga bracteosa - Riaz_2007_Chem.Biodivers_4_72
Author(s) : Riaz N , Nawaz SA , Mukhtar N , Malik A , Afza N , Ali S , Ullah S , Muhammad P , Choudhary MI
Ref : Chem Biodivers , 4 :72 , 2007
Abstract : Bractin A (=(2S,3S,4R,5E)-2-{[(2R)-2-hydroxydodecanoyl]amino}triacont-5-ene-1,3,4-triol; 1) and bractin B (=(2S,3S,4R,5E,8E)-2-{[(2R)-2-hydroxyhexacosanoyl]amino}pentadeca-5,8-diene-3,4,1 5-triol 1-O-beta-D-glucopyranoside; 2), new sphingolipids, and bractic acid (=(5Z,10Z,15Z)-2-decyl-4,7,8,12,13,17,18-heptahydroxy-20,23-dioxopentacosa-5,10,1 5-trienoic acid; 3), a long-chain polyhydroxy acid, were isolated from the whole plant Ajuga bracteosa along with four known diterpenoids 4-7. Their structures were deduced by spectral studies including 1D- and 2D-NMR spectroscopy. Compounds 1-3 displayed inhibitory potential against enzyme lipoxygenase, while compounds 4-7 inhibited cholinesterase enzymes in a concentration-dependent manner with IC(50) values in the range 10.0-33.0, 14.0-35.2, and 10.0-19.0 microM for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively. Lineweaver-Burk, and Dixon plots, and their secondary replots indicated that all compounds exhibit non-competitive type of inhibition with K(i) values in the range of 9.5-35.2, 15.2-36.0, and 11.6-20.5 microM, for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively.
ESTHER : Riaz_2007_Chem.Biodivers_4_72
PubMedSearch : Riaz_2007_Chem.Biodivers_4_72
PubMedID: 17256736

Title : Microbial transformation of the steroidal alkaloid dictyophlebine by Rhizopus stolonifer - Devkota_2007_Chem.Pharm.Bull.(Tokyo)_55_682
Author(s) : Devkota KP , Choudhary MI , Nawaz SA , Lannang AM , Lenta BN , Fokou PA , Sewald N
Ref : Chem Pharm Bull (Tokyo) , 55 :682 , 2007
Abstract : The microbial transformation of a steroidal alkaloid, dictyophlebine (1) with Rhizopus stolonifer (ATCC 10404) afforded three oxidized metabolites 2-4. Compound 2 was found to be a new product. These metabolites were structurally characterized on the basis of modern spectroscopic techniques. Their inhibitory activity towards acetyl- and butyrylcholinesterase has been evaluated and the new product 2 has been found to be more potent than the parent compound and other metabolites.
ESTHER : Devkota_2007_Chem.Pharm.Bull.(Tokyo)_55_682
PubMedSearch : Devkota_2007_Chem.Pharm.Bull.(Tokyo)_55_682
PubMedID: 17409573

Title : Isolation of four new pterocarpans from Zygophyllum eurypterum (Syn. Z. atriplicoides) with enzyme-inhibition properties - Ahmad_2006_Chem.Biodivers_3_996
Author(s) : Ahmad VU , Iqbal S , Nawaz SA , Choudhary MI , Farooq U , Ali ST , Ahmad A , Bader S , Kousar F , Arshad S , Tareen RB
Ref : Chem Biodivers , 3 :996 , 2006
Abstract : Four new pterocarpans, atricarpan A (=(-)-1,2-dihydroxy-4-(hydroxymethyl)-3,9-dimethoxypterocarpan; 1), atricarpan B (=(-)-2,3-ethylenedioxy)-1,4-dihydroxy-9-methoxypterocarpan; 2), atricarpan C (=(-)-1,9-dimethoxypterocarpan-3-carboxylic acid; 3), and atricarpan D (=(-)-2,9-dimethoxy-4-(5-oxohexyl)pterocarpan; 4) were isolated from the BuOH extract of the whole plant of Zygophyllum eurypterum. The structure elucidations of those compounds were based primarily on 1D- and 2D-NMR analysis, including COSY, HMBC, and HMQC correlations. Compounds 1-4 also inhibited butyrylcholinesterase (BChE; EC 3.1.1.8) enzyme in a concentration-dependent manner with IC(50) values between 12.5-65.0 microM. Similarly, compounds 1 and 4 inhibited lipoxygenase (LOX; EC 1.13.11.12) and acetylcholinesterase (AChE; EC 3.1.1.7) enzymes with IC50 values of 13.5 and 20.5 muM, respectively.
ESTHER : Ahmad_2006_Chem.Biodivers_3_996
PubMedSearch : Ahmad_2006_Chem.Biodivers_3_996
PubMedID: 17193332

Title : Microbial transformation and butyrylcholinesterase inhibitory activity of (-)-caryophyllene oxide and its derivatives - Choudhary_2006_J.Nat.Prod_69_1429
Author(s) : Choudhary MI , Siddiqui ZA , Nawaz SA , Atta ur R
Ref : Journal of Natural Products , 69 :1429 , 2006
Abstract : Microbial transformation of the sesquiterpene (-)-caryophyllene oxide (1) [(1R,4R,5R,9S)-4,5-epoxycaryophyllan-8(13)-ene] by a number of fungi, using a standard two-stage fermentation technique, has afforded as products (1R,4R,5R,9S)-4,5-dihydroxycaryophyllan-8(13)-ene (2), (1S,4R,5R,8S,9S)-clovane-5,9-diol (3), (1R,4R,5R,9S,11R)-4,5-epoxycaryophyllan-8(13)-en-15-ol (4), (1R,4R,5R,9S,11S)-4,5-epoxycaryophyllan-8(13)-en-14-ol (5), (1R,2S,4R,5R,9S)-4,5-epoxy-13-norcaryophyllan-8-one (6), (1R,4R,5R,8S,9S)-4,5-epoxycaryophyllan-13-ol (7), (1R,4R,5R,8S, 9S,13S)-caryolane-5,8,13-triol (8), (1R,3R,4R,5R,8S,9S)-4,5-epoxycaryophyllan-3,13-diol (9), and (1S,4R,5R,8S,9S)-clovane-5,9,12-triol (10). Metabolites 6 and 8-10 were found to be new compounds, as deduced on the basis of spectroscopic techniques. Compounds 1-10 were evaluated for butyrylcholinesterase inhibitory activity, and compound 5 exhibited an IC50 value of 10.9 +/- 0.2 microM.
ESTHER : Choudhary_2006_J.Nat.Prod_69_1429
PubMedSearch : Choudhary_2006_J.Nat.Prod_69_1429
PubMedID: 17067156

Title : New butyrylcholinesterase inhibitory triterpenes from Salvia santolinifolia - Mehmood_2006_Arch.Pharm.Res_29_195
Author(s) : Mehmood S , Riaz N , Nawaz SA , Afza N , Malik A , Choudhary MI
Ref : Arch Pharm Res , 29 :195 , 2006
Abstract : Slavins A (1) and B (2), the new amyrin type triterpenes, have been isolated from the chloroform soluble fraction of Salvia santolinifolia and assigned structures on the basis of spectral studies including 2D NMR. Both the compounds displayed inhibitory potential against the enzyme butyrylcholinesterase.
ESTHER : Mehmood_2006_Arch.Pharm.Res_29_195
PubMedSearch : Mehmood_2006_Arch.Pharm.Res_29_195
PubMedID: 16596990

Title : The microbial hydroxylation of levonorgestrel - Choudhary_2006_Nat.Prod.Res_20_1074
Author(s) : Choudhary MI , Atif M , Nawaz SA , Fatmi MQ , Atta ur R
Ref : Nat Prod Res , 20 :1074 , 2006
Abstract : The microbial transformation of levonorgestrel (1) by Cunningham elegans resulted in the formation of five hydroxylated metabolites, 13-ethyl-10beta, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one(2), 13-ethyl-6beta,17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (3) 13-ethyl 6beta, 10beta, 17beta-trihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (4) 13-ethyl-15alpha-17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (5) and 13-ethyl-11alpha, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4en-20-yn-3-one. The fermentation of one with Rhizopus stolonifer, Fusarium lini and Curvularia lunata afforded compound 2 as a major metabolise. These metabolites were structurally characterized on the basis of spectroScopic techniques. Metabolite 6 was identified as a new compound. Compounds 2 2 ad 5 displayed inhibitory activity against the acetylcholinesterase ( AChE, EC. 3.1.1.7) with IC50 values of 79.2 and 24.5 microM, respectively. The metabolites 2 and 5 also showed inhibitory activity against the butyryLcholinesterase ( BChE, E.C 3.1.1.8) with IC50 values ranging between 9.4 and 309.8 microM.
ESTHER : Choudhary_2006_Nat.Prod.Res_20_1074
PubMedSearch : Choudhary_2006_Nat.Prod.Res_20_1074
PubMedID: 17201044

Title : Isolation and cholinesterase-inhibition studies of sterols from Haloxylon recurvum - Ahmed_2006_Bioorg.Med.Chem.Lett_16_573
Author(s) : Ahmed E , Nawaz SA , Malik A , Choudhary MI
Ref : Bioorganic & Medicinal Chemistry Lett , 16 :573 , 2006
Abstract : Haloxysterols A-D (1-4), new C-24 alkylated sterols, have been isolated from the chloroform soluble fraction of Haloxylon recurvum, along with five known sterols 5-9, which are reported for the first time from this species. Their structures were determined by means of 1D- and 2D-NMR techniques. Compounds 1-9 inhibited cholinesterase enzymes in a concentration-dependent manner with K(i) values ranging between 0.85-25.5 and 1.0-19.0 microM against acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) enzymes, respectively. Lineweaver-Burk, Dixon plots and their secondary replots indicated that compounds 1-9 are non-competitive inhibitors of both AChE and BChE enzymes.
ESTHER : Ahmed_2006_Bioorg.Med.Chem.Lett_16_573
PubMedSearch : Ahmed_2006_Bioorg.Med.Chem.Lett_16_573
PubMedID: 16274989

Title : Phenolic constituents from Perovskia atriplicifolia - Perveen_2006_Nat.Prod.Res_20_347
Author(s) : Perveen S , Khan SB , Malik A , Tareen RB , Nawaz SA , Choudhary MI
Ref : Nat Prod Res , 20 :347 , 2006
Abstract : 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-beta-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.
ESTHER : Perveen_2006_Nat.Prod.Res_20_347
PubMedSearch : Perveen_2006_Nat.Prod.Res_20_347
PubMedID: 16644529

Title : Three new cholinesterase-inhibiting cis-clerodane diterpenoids from Otostegia limbata - Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
Author(s) : Ahmad VU , Khan A , Farooq U , Kousar F , Khan SS , Nawaz SA , Abbasi MA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 53 :378 , 2005
Abstract : Three new tricyclic cis-clerodane type diterpenoids trivially named as limbatolide A (1), limbatolide B (2) and limbatolide C (3) have been isolated from the roots of Otostegia limbata along with two known compounds; oleanic acid and beta-sitosterol. The structure elucidation of the new compounds was based primarily on two-dimensional (2D) NMR techniques. Compounds 1-3 displayed inhibitory potential in a concentration-dependent manner against acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) enzymes, respectively.
ESTHER : Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
PubMedSearch : Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
PubMedID: 15802835

Title : Synthesis and inhibitory potential towards acetylcholinesterase, butyrylcholinesterase and lipoxygenase of some variably substituted chalcones - Hasan_2005_J.Enzyme.Inhib.Med.Chem_20_41
Author(s) : Hasan A , Khan KM , Sher M , Maharvi GM , Nawaz SA , Choudhary MI , Atta ur R , Supuran CT
Ref : J Enzyme Inhib Med Chem , 20 :41 , 2005
Abstract : 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 microM against acetylcholinesterase, 16.0-23.1 microM against butyrylcholinesterase and 57.6-71.7 microM against lipoxygenase, respectively.
ESTHER : Hasan_2005_J.Enzyme.Inhib.Med.Chem_20_41
PubMedSearch : Hasan_2005_J.Enzyme.Inhib.Med.Chem_20_41
PubMedID: 15895683

Title : Syntheses and biological activities of chalcone and 1,5-benzothiazepine derivatives: promising new free-radical scavengers, and esterase, urease, and alpha-glucosidase inhibitors - Ansari_2005_Chem.Biodivers_2_487
Author(s) : Ansari FL , Umbreen S , Hussain L , Makhmoor T , Nawaz SA , Lodhi MA , Khan SN , Shaheen F , Choudhary MI
Ref : Chem Biodivers , 2 :487 , 2005
Abstract : A series of 2,4-diaryl-2,3,4,5-tetrahydro- (36-40) and 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines (25-35) have been synthesized from the corresponding chalcones 1-24. Both the benzothiazepines and chalcones were evaluated as DPPH free-radical scavengers and as inhibitors of cholinesterases, urease, and alpha-glucosidase. Compounds 2, 5, 6, 7, 10, 13, 18, 21, 36a, 37a, 37b, and 39a showed significant cholinesterase inhibiting activities. Among the 15 dihydro-1,5-benzothiazepines, 26, 32, and 35 exhibited significant radical-scavenging activities; and six tetrahydro-1,5-benzothiazepines (35, 36a, 36b, 37a, 37b, and 39a) were found to be inhibitors of AChE and BChE. Compounds 22, 25, 26, 33, 35, 36a, 37b, and 39a inhibited urease, and 25 and 27-31 were found to be potent inhibitors of alpha-glucosidase.
ESTHER : Ansari_2005_Chem.Biodivers_2_487
PubMedSearch : Ansari_2005_Chem.Biodivers_2_487
PubMedID: 17191997

Title : Microbial hydroxylation of pregnenolone derivatives - Choudhary_2005_Chem.Pharm.Bull.(Tokyo)_53_1455
Author(s) : Choudhary MI , Batool I , Shah SA , Nawaz SA , Atta ur R
Ref : Chem Pharm Bull (Tokyo) , 53 :1455 , 2005
Abstract : Pregnenolone and pregnenolone acetate were incubated with the fungi Cunninghamella elegans, Rhizopus stolonifer and Gibberella fujikuroi. Incubation of with C. elegans yielded metabolites, 3beta,7beta,11alpha-trihydroxypreg-5-en-20-one, 3beta,6alpha,11alpha,12beta,15beta-pentahydroxypreg-4-en-20-one and 3beta,6beta,11alpha-trihydroxypreg-4-en-20-one, while incubation with G. fujikuroi yielded two known metabolites, 3beta,7beta-dihydroxypregn-5-en-20-one and 6beta,15beta-dihydroxypreg-4-ene-3,20-dione. Metabolites and were found to be new. Fermentation of by C. elegans yielded four known oxidative metabolites, androsta-1,4-diene-3,17-dione, 6beta,15beta-dihydroxyandrost-4-ene-3,17-dione and 11alpha,15beta-dihydroxypreg-4-ene-3,20-dione. Fermentation of with R. stolonifer yielded two known metabolites, 11alpha-hydroxypreg-4-ene-3,20-dione and. Compounds were screened for their cholinesterase inhibitory activity in a mechanism-based assay.
ESTHER : Choudhary_2005_Chem.Pharm.Bull.(Tokyo)_53_1455
PubMedSearch : Choudhary_2005_Chem.Pharm.Bull.(Tokyo)_53_1455
PubMedID: 16272731

Title : Microbial transformation of (-)-isolongifolol and butyrylcholinesterase inhibitory activity of transformed products - Choudhary_2005_Bioorg.Med.Chem_13_1939
Author(s) : Choudhary MI , Musharraf SG , Nawaz SA , Anjum S , Parvez M , Fun HK , Atta ur R
Ref : Bioorganic & Medicinal Chemistry , 13 :1939 , 2005
Abstract : The microbial transformation of (-)-isolongifolol (1) by using the standard two-stage fermentation technique with Fusarium lini afforded polar oxygenated metabolites: 10-oxoisolongifolol (2), 10alpha-hydroxyisolongifolol (3), and 9alpha-hydroxyisolongifolol (4). Metabolites 3 and 4 were also formed with the incubation of 1 with Aspergillus niger. All three metabolites were found to be new. Compounds 3 and 4 inhibited butyrylcholinesterase enzyme in a concentration-dependent manner with IC50 values 13.6 and 299.5 microM, respectively. Compound 3 showed un-competitive mode of inhibition against butyrylcholinesterase with Ki value 15.0 microM. The structures of metabolites 2-4 were deduced on the basis of spectroscopic techniques and single-crystal X-ray diffraction techniques.
ESTHER : Choudhary_2005_Bioorg.Med.Chem_13_1939
PubMedSearch : Choudhary_2005_Bioorg.Med.Chem_13_1939
PubMedID: 15830442

Title : Butyrylcholinesterase inhibitory guaianolides from Amberboa ramosa - Khan_2005_Arch.Pharm.Res_28_172
Author(s) : Khan SB , Azhar Ul H , Perveen S , Afza N , Malik A , Nawaz SA , Shah MR , Choudhary MI
Ref : Arch Pharm Res , 28 :172 , 2005
Abstract : Phytochemical investigation of the whole plant of Amberboa ramosa led to the isolation of six sesquiterpene lactones which could be identified as 8alpha-hydroxy-11beta-methyl-1alphaH, 5alphaH, 6betaH, 7alphaH, 11alphaH-guai-10(14), 4(15)-dien-6, 12-olide(1), 3beta, 8alpha-dihydroxy-11alpha-methyl-1alphaH, 5alphaH, 6betaH, 7alphaH, 11betaH-guai-10(14), 4 (15)-dien-6, 12-olide (2), 3beta, 4alpha, 8alpha-trihydroxy-4beta-(hydroxymethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14), 11(13)-dien-6, 12-olide (3), 3beta, 4alpha, 8alpha-trihydroxy-4beta-(chloromethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11(13)-dien-6, 12-olide(4), 3beta, 4alpha, dihydroxy-4beta-(hydroxymethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11(13)-dien-6, 12-olide(5), 3beta, 4alpha-dihydroxy-4beta-(chloromethyl)-8alpha-(4-hydroxymethacrylate)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11 (13)-dien-6,12-olide (6) by spectroscopic methods. All of them showed inhibitory potential against butyrylcholinesterase.
ESTHER : Khan_2005_Arch.Pharm.Res_28_172
PubMedSearch : Khan_2005_Arch.Pharm.Res_28_172
PubMedID: 15789746

Title : Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties - Choudhary_2005_Biochem.Biophys.Res.Commun_334_276
Author(s) : Choudhary MI , Nawaz SA , Ul-Haq Z , Lodhi MA , Ghayur MN , Jalil S , Riaz N , Yousuf S , Malik A , Gilani AH , ur-Rahman A
Ref : Biochemical & Biophysical Research Communications , 334 :276 , 2005
Abstract : The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2 microm for AChE and BChE, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that compounds 1, 3, and 5 are the linear mixed-type inhibitors of AChE, while 2 and 4 are non-competitive inhibitors of AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were found to be non-competitive inhibitors of BChE with K(i) values ranging between 27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5 extend up to the catalytic triad. A comparison of the docking results showed that all ligands generally adopt the same binding mode and lie parallel to the surface of the gorge. The superposition of the docked structures demonstrated that the non-flexible skeleton of the ligands always penetrates the aromatic gorge through the six-membered ring A, allowing their simultaneous interaction with more than one subsite of the active center. The affinity of ligands with AChE was found to be the cumulative effects of number of hydrophobic contacts and hydrogen bonding. Furthermore, all compounds also displayed dose-dependent (0.005-1.0 mg/mL) spasmolytic and Ca2+ antagonistic potentials in isolated rabbit jejunum preparations, compound 4 being the most active with an ED50 value of 0.09 +/- 0.001 mg/mL and 0.22 +/- 0.01 microg/mL on spontaneous and K+ -induced contractions, respectively. The cholinesterase inhibitory potential along with calcium antagonistic ability and safe profile in human neutrophil viability assay could make compounds 1-5 possible drug candidates for further study to treat Alzheimer's disease and associated problems.
ESTHER : Choudhary_2005_Biochem.Biophys.Res.Commun_334_276
PubMedSearch : Choudhary_2005_Biochem.Biophys.Res.Commun_334_276
PubMedID: 16108094

Title : Haloxylines A and B, antifungal and cholinesterase inhibiting piperidine alkaloids from Haloxylon salicornicum - Ferheen_2005_Chem.Pharm.Bull.(Tokyo)_53_570
Author(s) : Ferheen S , Ahmed E , Afza N , Malik A , Shah MR , Nawaz SA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 53 :570 , 2005
Abstract : Haloxylines A (1) and B (2), new piperidine alkaloids, have been isolated from the chloroform soluble fraction of Haloxylon salicornicum and their structures elucidated by spectroscopic techniques including 2D-NMR. Both the compounds displayed antifungal and cholinesterase enzymes inhibitory potentials.
ESTHER : Ferheen_2005_Chem.Pharm.Bull.(Tokyo)_53_570
PubMedSearch : Ferheen_2005_Chem.Pharm.Bull.(Tokyo)_53_570
PubMedID: 15863932

Title : Juliflorine: a potent natural peripheral anionic-site-binding inhibitor of acetylcholinesterase with calcium-channel blocking potential, a leading candidate for Alzheimer's disease therapy - Choudhary_2005_Biochem.Biophys.Res.Commun_332_1171
Author(s) : Choudhary MI , Nawaz SA , Zaheer ul H , Azim MK , Ghayur MN , Lodhi MA , Jalil S , Khalid A , Ahmed A , Rode BM , Atta ur R , Gilani AU , Ahmad VU
Ref : Biochemical & Biophysical Research Communications , 332 :1171 , 2005
Abstract : The alkaloid juliflorine (1) from Prosopis juliflora inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC50 values 0.42 and 0.12 microM, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that the nature of inhibition was purely of non-competitive type with Ki values 0.4 and 0.1 microM, against AChE and BChE, respectively. By molecular docking studies compound 1 was found to be ideally spaced inside the aromatic gorge of AChE with rings A/B remaining at the top and rings C/D penetrating deep into the gorge, that might be due to the greater hydrophobicity of rings C/D as compared to rings A/B, allowing their simultaneous interaction with the peripheral anionic and quaternary ammonium-binding sites. The 1-AChE complex was found to be stabilized by hydrophobic contacts, hydrogen bonding, and pi-pi stacking between the compound 1 and amino acid residues of the aromatic gorge of AChE. Amino acid residues Tyr70, Asp72, Tyr121, Trp279, and Tyr334 of the peripheral anionic site (PAS) of AChE were found to be exclusively involved in the hydrophobic contacts with compound 1 that might be responsible for the competitive mode of inhibition. Compound 1 also showed dose-dependent (30-500 microg/mL) spasmolytic and Ca2+-channel blocking activities in isolated rabbit jejunum preparations. The cholinesterase inhibitory potential along with calcium-channel blocking activity of compound 1 and safe profile in human neutrophils viable assay could make it a possible drug candidate for Alzheimer's disease.
ESTHER : Choudhary_2005_Biochem.Biophys.Res.Commun_332_1171
PubMedSearch : Choudhary_2005_Biochem.Biophys.Res.Commun_332_1171
PubMedID: 16021692

Title : Cholinesterase inhibitory pregnane-type steroidal alkaloids from Sarcococca hookeriana - Choudhary_2005_Steroids_70_295
Author(s) : Choudhary MI , Devkota KP , Nawaz SA , Ranjit R , Atta ur R
Ref : Steroids , 70 :295 , 2005
Abstract : The bioassay-guided phytochemical investigation on Sarcococca hookeriana have resulted in the isolation of four new pregnane-type steriodal alkaloids: hookerianamide-D [(2'E,20S)-20-(N,N-formyl(methyl)amino)-3beta-(3',4'-dimethyl-2'-pentenamido)-5al pha-pregnane] (1), hookerianamide-E [(2'E,20S)-20-(N,N-dimethylamino)-3beta-(senecioylamino)-5alpha-pregn-14-en-2beta -O-acetate] (2), hookerianamide-F [(2'E,20S)-20-(N-methylamino)-3beta-(tigloylamino)-5alpha-pregn-2,14-dien-4-one] (3), and hookerianamide-G [(20S)-20-(N,N-dimethylamino)-3beta-(N-methylbenzamido)-5alpha-pregn-4beta-O-acet ate] (4), along with five known alkaloids 5-9. Their structures were determined by spectroscopic analysis. These steroidal alkaloids and chemically derived derivatives of compound 5 have displayed varying degree of inhibitory activities against acetylcholinesterase and butyrylcholinesterase enzymes in a concentration-dependent fashion, with the IC(50) values ranging from 1.5 to 148.2 and 0.6 to 100.2 microM, respectively.
ESTHER : Choudhary_2005_Steroids_70_295
PubMedSearch : Choudhary_2005_Steroids_70_295
PubMedID: 15784284

Title : Cholinesterase-inhibiting withanolides from Ajuga bracteosa - Riaz_2004_Chem.Biodivers_1_1289
Author(s) : Riaz N , Malik A , Nawaz SA , Muhammad P , Choudhary MI
Ref : Chem Biodivers , 1 :1289 , 2004
Abstract : Three new withanolides, bracteosin A (= (22R)-5beta,6beta : 22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxyergost-24-ene-1,26-dione; 1), bracteosin B (= (22R)-5beta,6beta : 22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxy-1,26-dioxoergost-24-en-19-oic acid; 2), and bracteosin C (= (22R)-22,26-epoxy-4beta,6beta,27-trihydroxy-3beta-methoxyergost-24-ene-1,26-dione ; 3), have been isolated from the whole plants of Ajuga bracteosa. Their structures were deduced by spectral analysis, including 1D- and 2D-NMR techniques. In addition, dihydroclerodin-1, clerodinin A, lupulin A, and dihydroajugapitin have also been isolated for the first time from this species. Compounds 1-3 exhibited evident inhibitory potential against cholinesterase enzymes in a concentration-dependent fashion.
ESTHER : Riaz_2004_Chem.Biodivers_1_1289
PubMedSearch : Riaz_2004_Chem.Biodivers_1_1289
PubMedID: 17191906

Title : New pregnane-type steroidal alkaloids from Sarcocca saligna and their cholinesterase inhibitory activity - Atta_2004_Steroids_69_735
Author(s) : Atta ur R , Feroz F , Naeem I , Zaheer ul H , Nawaz SA , Khan N , Khan MR , Choudhary MI
Ref : Steroids , 69 :735 , 2004
Abstract : 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.
ESTHER : Atta_2004_Steroids_69_735
PubMedSearch : Atta_2004_Steroids_69_735
PubMedID: 15685740

Title : Enzyme inhibiting lignans from Vitex negundo - Azhar_2004_Chem.Pharm.Bull.(Tokyo)_52_1269
Author(s) : Azhar Ul H , Malik A , Anis I , Khan SB , Ahmed E , Ahmed Z , Nawaz SA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 52 :1269 , 2004
Abstract : Two new lignans trivially named negundins A (1) and B (2), were isolated along with (+)-diasyringaresinol (3), (+)-lyoniresinol (4), vitrofolal E (5) and vitrofolal F (6), reported for the first time from this species. The structures of the new compounds were established through spectral studies. Compound 2 showed potent inhibitory activity against lipoxygenase enzyme, while 5 showed moderate activity against butyryl-cholinesterase.
ESTHER : Azhar_2004_Chem.Pharm.Bull.(Tokyo)_52_1269
PubMedSearch : Azhar_2004_Chem.Pharm.Bull.(Tokyo)_52_1269
PubMedID: 15520511

Title : New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Cocculus pendulus - Atta-Ur-Rahman_2004_Chem.Pharm.Bull.(Tokyo)_52_802
Author(s) : Atta-ur-Rahman , Atia-Tul-Wahab , Nawaz SA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 52 :802 , 2004
Abstract : Phytochemical investigation on Cocculus pendulus (J. R. & G. FORST.) resulted in the isolation of two new and three known bisbenzylisoquinoline alkaloids. The structures of the new alkaloids, kurramine-2'-beta-N-oxide (1) and kurramine-2'-alpha-N-oxide (2), were elucidated with the help of spectroscopic techniques. The cholinesterase inhibitory activities of these bisbenzylisoquinoline alkaloids are reported here for the first time.
ESTHER : Atta-Ur-Rahman_2004_Chem.Pharm.Bull.(Tokyo)_52_802
PubMedSearch : Atta-Ur-Rahman_2004_Chem.Pharm.Bull.(Tokyo)_52_802
PubMedID: 15256699

Title : Cholinesterase inhibiting withanolides from Withania somnifera - Choudhary_2004_Chem.Pharm.Bull.(Tokyo)_52_1358
Author(s) : Choudhary MI , Yousuf S , Nawaz SA , Ahmed S , Atta ur R
Ref : Chem Pharm Bull (Tokyo) , 52 :1358 , 2004
Abstract : A total of two new (1, 2) and four known (3-6) withanolides were isolated from the whole plant of Withania somnifera. Their structures were elucidated on the basis of spectroscopic techniques and were characterized as 6alpha,7alpha-epoxy-3beta,5alpha,20beta-trihydroxy-1-oxowitha-24-enolide (1), 5beta,6beta-epoxy-4beta,17alpha,27-trihydroxy-1-oxowitha-2,24-dienolide (2), withaferin-A (3), 2,3-dihydrowithaferin-A (4), 6alpha,7alpha-epoxy-5alpha,20beta-dihydroxy-1-oxowitha-2,24-dienolide (5), and 5beta,6beta-epoxy-4beta-hydroxy-1-oxowitha-2,14,24-trienolide (6), respectively. Compounds 2, 3, 5, and 6 displayed inhibitory potential against butyrylcholinesterase, but only compounds 3, 4, and 6 were found to be active against acetylcholinesterase.
ESTHER : Choudhary_2004_Chem.Pharm.Bull.(Tokyo)_52_1358
PubMedSearch : Choudhary_2004_Chem.Pharm.Bull.(Tokyo)_52_1358
PubMedID: 15520512

Title : New steroidal alkaloids from Sarcococca saligna - Atta_2003_Nat.Prod.Res_17_235
Author(s) : Atta ur R , Feroz F , Zaheer ul H , Nawaz SA , Khan MR , Choudhary MI
Ref : Nat Prod Res , 17 :235 , 2003
Abstract : Two new steroidal alkaloids, salonine-A [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-5alpha-pregn-14-en-2beta,4beta -diol] (1), and salonine-B [(20S)-20-(N,N-dimethylamino)-3beta-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.
ESTHER : Atta_2003_Nat.Prod.Res_17_235
PubMedSearch : Atta_2003_Nat.Prod.Res_17_235
PubMedID: 12822900

Title : Cholinesterase Inhibitory Constituents from Onosma hispida - Ahmad_2003_Chem.Pharm.Bull.(Tokyo)_51_412
Author(s) : Ahmad I , Anis I , Malik A , Nawaz SA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 51 :412 , 2003
Abstract : Hispidone, a new flavanone, has been isolated from Onosma hispida and assigned the structure (2S)-5,2'-dihydroxy-7,4',5'-trimethoxyflavanone (1) by spectroscopic methods. In addition, (2S)-5,2'-dihydroxy-7,5'-dimethoxyflavanone (2), benzoic acid (3), and 4-hydroxy benzoic acid (4) are also reported for the first time from this species.
ESTHER : Ahmad_2003_Chem.Pharm.Bull.(Tokyo)_51_412
PubMedSearch : Ahmad_2003_Chem.Pharm.Bull.(Tokyo)_51_412
PubMedID: 12672994