Mumtaz Ali

Extractives in bark of different conifer species growing in Pakistan

Abstract The amount and composition of lipophilic and hydrophilic extractives, including proanthocyanidins, has been analysed as a first screening in the bark of six Pakistani coniferous tree species, namely Pinus wallichiana, Pinus roxburghii, Pinus gerardiana, Abies pindrow, Taxus fuana and Cedrus deodara. The predominant lipophilic extractives were common fatty and resin acids, fatty alcohols and sterols. In all bark samples, short-chain fatty acids were more abundant than long-chain fatty acids. Generally, the amount of free fatty acids was also larger than the amount of triglycerides. Oleic acid was the most common fatty acid, except in C. deodara, where lignoceric acid dominated. The largest amounts of fatty acids and fatty alcohols were found in P. wallichiana and P. gerardiana. P. gerardiana contained an exceptionally large amount of resin acids, approximately 3% of the bark weight, compared to the other species. The amount of free sterols was approximately at the same level or larger than the amount of steryl esters in most samples. In addition to proanthocyanidins, different known lignans, stilbenes, ferulates and flavonoids were generally predominant amongst the hydrophilic extractives. Resveratrol glycoside was abundant in P. wallichiana, while C. deodara and P. gerardiana contained large amounts of lignans and lignan derivatives. All bark extracts contained large amounts of proanthocyanidin-related catechin and its derivatives. Furthermore, C. deodara and P. roxburghii contained quite large amounts of taxifolin. In particular, P. wallichiana and A. pindrow are potential rich sources of proanthocyanidins, representing approximately 16% and 5% of the bark weight, respectively.

Pistagremic acid a new leishmanicidal triterpene isolated from Pistacia integerrima Stewart.

The present study was designed to investigate the whole plant of Pistacia integerrima Stewart in order to examine the pharmacological basis of the use of the plant in folk medicine for the treatment of infectious diseases and disorder. Phytochemical and pharmacological studies led to the isolation of a new triterpene pistagremic acid (3-methyl-7-(4,4,10,13,14-pentamethyl-3-2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-oct-3-enoic). Pistagremic acid showed significant leishmanicidal activity (IC50: 6.71 ± 0.09 µM) against Leishmania major (DESTO) promastigotes in comparison to standard compound amphotericin B (IC50: 0.21 ± 0.06 µM).

Morphological analysis of the antimicrobial action of silver and gold nanoparticles stabilized with ceftriaxone on Escherichia coli using atomic force microscopy

The antibiotic ceftriaxone was conjugated to Ag and Au nanoparticles. The activity of the conjugates against Escherichia coli ATCC 8739 was compared to that of pure ceftriaxone and of unconjugated nanoparticles using atomic force microscopy and more conventional techniques such as the agar well diffusion method. Conjugation to Ag nanoparticles increased the antibacterial activity of ceftriaxone by about 2 times, and conjugation to Au by about 6 times. Conjugation also appeared to improve the kinetics of the antibiotic. Thus, for example, membrane damage was barely evident two hours after contacting a cell culture with pure ceftriaxone. In the same time, Ag conjugates severely damaged membranes and Au conjugates completely disrupted the cell morphology.

Neurologically Potent Molecules from Crataegus oxyacantha; Isolation, Anticholinesterase Inhibition, and Molecular Docking

Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer’s disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman’s assay with Galantamine as standard drug. Total of nine (1–9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source. Important natural products like β-Sitosterol-3-O-β-D-Glucopyranoside (3), lupeol (4), β-sitosterol (5), betulin (6), betulinic acid (7), oleanolic acid (8), and chrysin (9) have also been isolated from C. oxyacantha. Overall, all the compounds exhibited an overwhelming acetylcholinesterase (AChE) inhibition potential in the range 5.22–44.47 μM. The compound 3 was prominent AChE inhibitor with IC50 value of 5.22 μM. Likewise, all the compounds were also potent in butyrylcholinesterase (BChE) inhibitions with IC50s of up to 0.55–15.36 μM. All the compounds, except 3, were selective toward BChE. Mechanism of the inhibition of both the enzymes were further studied by docking procedures using Genetic Optimization for Ligand Docking suit v5.4.1. Furthermore, computational blood brain barrier prediction of the isolated compounds suggest that these are BBB+.

Anti-ulcer xanthones from the roots of Hypericum oblongifolium Wall

Three new xanthones, hypericorin C (1), hypericorin D (2) and 3,4-dihydroxy-5-methoxyxanthone (3), along with eight known compounds; 2,3-dimethoxyxanthone (4), 3,4-dihydroxy-2-methoxyxanthone (5), 3,5-dihydroxy-1-methoxyxanthone (6), 3-acetylbetulinic acid (7), 10H-1,3-dioxolo[4,5-b]xanthen-10-one (8), 3-hydroxy-2-methoxyxanthone (9), 3,4,5-trihydroxyxanthone (10) and betulinic acid (11) were isolated from the roots of Hypericum oblongifolium. The structures of the new compounds 1, 2 and 3 were deduced by spectroscopic techniques [ESI MS, (1)H NMR, (13)C NMR, and 2D NMR (HMQC, HMBC, COSY and NOESY)]. The entire series of compounds were evaluated for anti-ulcer activity.

Anti-inflammatory xanthones from the twigs of Hypericum oblongifolium wall.

Two new xanthonolignoids, hypericorin A (1) and hypericorin B (2), along with five known new source compounds, a xanthonolignoid, kielcorin (3), 4-hydroxy-2,3-dimethoxyxanthone (4), 3,4,5-trihydroxyxanthone (5), 1,3-dihydroxy-5-methoxyxanthone ( 6) and 1,3,7-trihydroxyxanthone (7), were isolated from the stems (twigs) of Hypericum oblongifolium Wall. The structures of the new compounds were deduced on the basis of spectroscopic techniques (EI-MS, HREI-MS, (1)H NMR, (13)C NMR, HMQC, HMBC, and NOESY). We also report herein for the first time the single crystal X-ray structure of compound 6. Compounds 1- 7 were screened for their IN VITRO anti-inflammatory (respiratory burst) inhibiting activities using isolated human neutrophils; compounds 1, 2, 3, 5, and 7 showed significant activities (IC (50) = 816.23 ± 73.30, 985.20 ± 55.80, 965.21 ± 65.80, 907.20 ± 50.80, 975.20 ± 81.10 µM, respectively), compound 6 showed moderate activity (IC (50) = 2500.85 ± 50.50 µM), while compound 4 was totally inactive at 1000 µg/mL as compared to the positive control used, indomethacin (IC (50) = 757.99 ± 5.90 µM), and aspirin (IC (50) = 279.44 ± 4.40 µM). Compound 4 was also inactive in comparison with other tested Hypericum compounds.

A new rosane-type diterpenoid from Stachys parviflora and its density functional theory studies

A new rosane-type diterpenoid (1) has been isolated from the chloroform fraction of Stachys parviflora. Structure of 1 was proposed based on 1D and 2D NMR techniques including correlation spectroscopy, heteronuclear multiple quantum coherence, heteronuclear multiple bond correlation and nuclear Overhauser effect spectroscopy. A theoretical model for the electronic and spectroscopic properties of compound 1 is also developed. The geometries and electronic properties were modelled at B3LYP/6-31G* and the theoretical scaled spectroscopic data correlate nicely with the experimental data.

Isolation, crystal structure determination and cholinesterase inhibitory potential of isotalatizidine hydrate from Delphinium denudatum

Abstract Context: Delphinium denudatum Wall (Ranunculaceae) is a rich source of diterpenoid alkaloids and is widely used for the treatment of various neurological disorders such as epilepsy, sciatica and Alzheimer’s disease. Objective: The present study describes crystal structure determination and cholinesterase inhibitory potential of isotalatazidine hydrate isolated from the aerial part of Delphinium denudatum. Materials and methods: Phytochemical investigation of Delphinium denudatum resulted in the isolation of isotalatazidine hydrate in crystalline form. The molecular structure of the isolated compound was established by X-ray diffraction. The structural data (bond length and angles) of the compound were calculated by Density Functional Theory (DFT) using B3LYP/6-31 + G (p) basis set. The cholinesterase inhibitory potential of the isolated natural product was determined at various concentrations (62.5, 125, 250, 500 and 1000 μg/mL) followed by molecular docking to investigate the possible inhibitory mechanism of isotalatazidine hydrate. Results: The compound crystallized in hexagonal unit cell with space group P65. Some other electronic properties such as energies associated with HOMO-LUMO, band gaps, global hardness, global electrophilicity, electron affinity and ionization potential were also calculated by means of B3LYP/6-31 + G (p) basis set. The compound showed competitive type inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 12.13 μM and 21.41 μM, respectively. Discussion and conclusion: These results suggest that isotalatazidine hydrate is a potent dual cholinesterase inhibitor and can be used as a target drug in Alzheimer diseases. This is first report indicating isotalatazidine hydrate with anticholinesterase potential.

Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum

Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.

In vitro enzyme inhibition activities of Myrtus communis L.

The crude methanolic extract and chloroform, ethyl acetate and n-butanol fractions of Myrtus communis L. were examined as inhibitors of acetylcholinesterase, butyrylcholinesterase and lipoxygenase. A significant enzyme inhibition activity (81 to 91%) was shown by the crude methanolic extract and its fractions against acetylcholinesterase, while high to outstanding enzyme inhibitory activity (72.5 to 99%) was shown against butyrylcholinesterase. The crude methanolic extract and its various fractions also demonstrated significant activity (79 to 94.5%) against lipoxygenase.