Mohammad Arfan

Urease inhibitors from Hypericum oblongifolium WALL.

The bioassay-guided fractionation of H. oblongifolium has led to the isolation of potent urease inhibitors 1–3. The structures were elucidated by NMR and mass spectroscopic techniques. Compound 2 showed a potent enzyme inhibition activity (IC50 20.96 ± 0.93), which is comparatively higher than that for the standard thiourea (IC50 21.01 ± 0.51 μM). Compounds 1 and 3 also showed a significant activity, with IC50 37.95 ± 1.93 and 138.43 ± 1.23 μM, respectively. The sub crude fractions (F1, F2, F3, and F4) were tested in vitro for their urease inhibition activity. Fractions F2 and F4 showed significant activity with IC50 140.37 ± 1.93 and 167.43 ± 3.03 μM, respectively.

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.

Immunosuppressive withanolides from Withania coagulans.

Six new withanolides, withacoagulins A–F (1–6, resp.), together with ten known withanolides, 7–16, were isolated from the aerial parts of Withania coagulans. Their structures were determined by spectroscopic techniques including 1D‐ and 2D‐NMR (1H, 13C, HMQC, and HMBC) and MS experiments. These compounds, including the crude extracts of this herb, exhibited strong inhibitory activities on the T‐ and B‐cell proliferation.

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).

Identification of novel quinazolin-4(3H)-ones as inhibitors of thermolysin, the prototype of the M4 family of proteinases

A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilizing a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC(50) values ranging from 0.0115 microM (compound 3) to 122,637 microM (compound 29). Compound 3 [3-phenyl-2-(trifluoromethyl) quinazolin-4(3H)-one] (IC(50)=0.0115 microM) and compound 35 [3-(isopropylideneamino)-2,2-dimethyl-2,3-dihydroquinazolin-4 (1H)-one] (IC(50)=0.2477 microM) were found to be the most potent inhibitors.

In-vivo antinociceptive, anti-inflammatory and antipyretic activity of pistagremic acid isolated from Pistacia integerrima

The current study was designed to explore the antinociceptive, antiinflammatory and antipyretic activity of pistagremic acid (PA), isolated from Pistacia integerima bark in various animal paradigms. The results illustrated significant inhibition of noxious stimulation in acetic acid induced writhing test with maximum effect of 68% at 10mg/kg i.p. In tail immersion test, pretreatment with PA demonstrated marked activity during various assessment times in a dose dependent manner. The maximum pain inhibition was 59.46% at 10mg/kg i.p. after 90 min of PA treatment. However, the injection of naloxone did not antagonize this induced effect. PA significantly ameliorated post carrageenan induced edema dose dependently during various stages of inflammation. The effect was most dominant (60.02%) after 3(rd) h of drug administration when examined for 5h. Similarly, it provoked dose dependent antipyretic effect in febrile mice with maximum of 60.04% activity at 10mg/kg i.p. after 3rd hour of PA post treatment. Furthermore, molecular docking was carried out to understand the binding mode of PA. From the docking study it was observed that PA fits well in the active site of COX-2 enzyme due to hydrogen and hydrophobic moiety interactions to the important active site of molecule. In conclusion, PA possesses strong peripheral and central antinociceptive activity independent of opioidergic effect which was augmented by its anti-inflammatory and antipyretic activities.

Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α

Bergenin is an isocoumarin natural product which aides in fat loss, healthy weight maintenance, enhancing the lipolytic effects of norepinephrine, inhibiting the formation of interleukin 1α and cyclooxygenases-2. Here we describe the anti-inflammatory activity of new bergenin derivatives 1-15 in the respiratory burst assay. Bergenin was isolated from the crude extract of Mallotus philippenensis after repeated column chromatography and was then subjected to chemical derivatization. The structures of all compounds were elucidated by NMR and mass spectroscopic techniques. Compound 2 was also studied using single crystal X-ray diffraction. Compounds 4, (54.5±2.2%) 5 (47.5±0.5%) 5, and 15 (86.8±1.9%) showed significant (P≤0.005) NO inhibitory activities whereas 6, 7, 11, 12 and 13 displayed moderate inhibitory activities that ranges between 16% and 31%. Furthermore compounds 4 and 15, were discovered as significant (P≤0.005) TNF-α inhibitors with 98% and 96% inhibition, respectively, while compounds 3, 5, 7, 8, 11, and 12 showed low level of TNF-α inhibition (0.4-28%). Compounds 8, 13 and 15 exhibited moderate anti-inflammatory IC(50) activities with 212, 222, and 253 μM, respectively, compared to the standard anti-inflammatory drug indomethacin as well as the parent bergenin compound. No cytotoxic effects could be detected when the compounds were tested on 3T3 cells up to concentrations of 100 μM.

Isolation, spectroscopic and density functional theory studies of 7-(4-methoxyphenyl)-9H-furo[2,3-f]chromen-9-one: a new flavonoid from the bark of Millettia ovalifolia.

The phytochemical examination of chloroform soluble fraction (FX2) of methanolic extract of bark of Millettia ovalifolia yielded a new flavonoid; 7-(4-methoxyphenyl)-9H-furo [2,3-f]chromen-9-one (1). Compound 1 is characterized by spectroscopic analytical techniques such as UV, IR, 1D, 2D NMR spectroscopy, and mass spectrometry. A theoretical model is also developed for obtaining geometric, electronic and spectroscopic properties of 1. The geometry optimization and harmonic vibration simulations have been carried out at B3LYP/6-31G(d,p). The vibrational spectrum of compound 1 shows nice correlation with the experimental IR spectrum, through a scaling factor of 0.9613. (1)H and (13)C NMR chemical shifts are simulated using Cramers re-parameterized function WP04 at 6-31G(d,p) basis set, and correlate nicely with the experimental chemical shifts.

Analgesic and anti-inflammatory activities of 11-O-galloylbergenin

AIMS OF THE STUDY Current study was designed to explore the analgesic and anti-inflammatory effects of a constituent isolated from Mallotus philippinensis, in order to validate its folk use. MATERIALS AND METHODS 11-O-galloylbergenin was isolated from ethanolic extract of Mallotus philippinensis. Analgesic and anti-inflammatory activities of the test compound were assessed using formalin test and carrageenan-induced paw edema models. RESULTS 11-O-galloylbergenin showed significant analgesic activity at doses of 20 and 40 mg/kg against formalin test in rats. Similarly, 11-O-galloylbergenin exhibited significant anti-inflammatory activity in carrageenan-induced paw edema model at doses of 10, 20 and 30 mg/kg. CONCLUSION 11-O-galloylbergenin has demonstrated its significant potential to be further investigated for its discovery as a new lead compound for management of pain and inflammation.

Antiplasmodial Isoflavanones from the Roots of Sophora mollis

Six new prenylated isoflavanones named sophoronols A-F (1-6), together with eight phenolic constituents, were isolated from the roots of Sophora mollis. Their structures and stereochemistry were established by 1D and 2D NMR techniques, especially HMBC and NOESY as well as CD results. Componds 3 and 5 exhibited moderate anitplasmodial activity against the CQS D10 strain of Plasmodium falciparum, with IC(50) values of 12.9 and 12.8 microM, respectively.