Said Nadeem

Anti-inflammatory activities of Sieboldogenin from Smilax china Linn.: Experimental and computational studies

ETHNOPHARMACOLOGICAL RELEVANCE Smilax china Linn. is extensively used in traditional Chinese medicine (TCM) as well as in Pakistan for several medicinal purposes including their use in inflammatory disorders. AIM OF THE STUDY The aims of the current study were to validate and assess the folk use of Smilax china Linn. on pharmacological grounds using the isolated compound at molecular, in vivo and computational levels. MATERIALS AND METHODS Seiboldogenin was isolated from ethyl acetate fraction of the plant crude extract. In vitro lipoxygenase and in vivo carrageenan-induced hind paw oedema models were used in experimental studies while molecular docking technique was used to conduct computational study. RESULTS Sieboldogenin showed significant lipoxygenase inhibition (IC50: 38 microM). It also exhibited significant inhibition (p<0.05) of carrageenan-induced hind paw oedema at the doses of 10 and 50mg/kg. Computational molecular docking showed its molecular interaction with important amino acid residues in the catalytic site of lipoxygenase, revealing its potential binding mode at molecular level. CONCLUSIONS Sieboldogenin seems to be a potential new anti-inflammatory compound responsible for anti-inflammatory activities of Smilax china Linn. Its in vitro and in vivo inflammatory activities are in good agreement with the folk medicinal use of Smilax china Linn. in inflammatory disorders.

Chapter 5 – Recent Advances in the Dimroth Rearrangement: A Valuable Tool for the Synthesis of Heterocycles

Publisher Summary The Dimroth rearrangement (DR) is a translocation of two heteroatoms in a heterocyclic system, with or without changing its ring structure. The conversion of a heterocycle to a rearranged isomeric product can give one or two isomers via anintermediate, which selectively or specifically forms one of them as the major one. The stability of the rearranged product is the driving force for its formation, which may lead to the preference of one isomer. The heteroatoms which exchange positions in the rearrangement are S, N, O, and Se. DR can be divided into two types based on the positions of the translocating heteroatom(s): either both in the ring or one in the ring and the other located in an exocyclic position of that ring. This chapter discusses the translocation of heteroatoms between rings in fused heterocycles, and the translocation of exo-and endo-heteroatoms within a heterocyclic ring. In the process of rearrangement by translocation of heteroatoms between rings in fused heterocycles, the translocated heteroatoms are part of the ring. The translocation process changes the position of the heteroatom or the substituent on that ring leading to either a retained or a changed ring structure. The presence of a heteroatom within a five-membered ring and also at an exocyclic position of the adjacent ring is a promoting factor for the rearrangement. In the translocation of exo-and endocyclic heteroatoms in heterocyclic rings the translocation of heteroatom X (endocyclic in the ring) and Y (exocyclic to the ring) takes place during the rearrangement. All the processes are driven by the stability of the product, solvent, aromaticity of the ring, heteroatom valence, and bulkiness of the substituent.

Structural insights to investigate Conypododiol as a dual cholinesterase inhibitor from Asparagus adscendens

The main aim of the current study was to explore molecular insights for potentially new dual cholinesterase inhibitor(s) from Asparagus adscendens via molecular docking. This medicinal plant is traditionally used as a nerve tonic and remedy for memory impairments. Conypododiol was isolated from the chloroform fraction of methanolic extract of A. adscendens, based on bioactivity guided isolation. Conypododiol exhibited significant inhibition of both acetylcholinesterase and butyrylcholinesterase, having the IC(50) values 2.17 ± 0.1 μM and 11.21 ± 0.1 μM, respectively. IC(50) values of the standard compound Galanthamine for both the enzymes were 0.537 ± 0.018 μM and 8.6 ± 0.27 μM, respectively. Based on MTT cytotoxicity assay, Conypododiol was found safe against LCMK-2 monkey kidney epithelial cells and mice hepatocytes. Molecular docking studies revealed the hydrogen bonding interactions of Conypododiol with His440 and Ser200 at esteratic site (ES), and also with Tyr334 at peripheral anionic site (PAS) of the aromatic gorge of acetylcholinesterase. Simultaneous contacts of Conypododiol with PAS and ES shows its significance as a bivalent ligand. This preliminary study highlighted the potential of Conypododiol to be further developed and modified as new lead compound identified by its folk use.

Hautriwaic acid as one of the hepatoprotective constituent of Dodonaea viscosa.

It is widely known that hepatitis and its complications such as cirrhosis or hepatocellular carcinoma are one of the major health problems of the world especially since no specific treatment is available. In the present study we investigated the hepatoprotective potential of the methanolic extract of the whole plant of Dodonaea viscosa and its ethyl acetate, aqueous, butanol and n-hexane fractions against carbon tetrachloride (CCl₄) induced hepatoxicity in rats. Hepatoprotection was assessed in terms of reduction in serum enzymes (ALT, AST, and ALP) that occur after CCl₄ injury, and by histopathology and immunohistochemistry. The methanolic extract reduced the serum enzyme level (ALT, AST, and ALP) down to control levels despite CCl₄ treatment. It also reduced the CCl₄-induced damaged area to 0% as assessed by histopathology. The CD68+ macrophages were also reduced in number around the central vein area by the methanolic extract. These hepatoprotective effects were better than the positive control silymarin. Similar hepatoprotective activities were found with the ethyl acetate, and aqueous fractions of the methanolic extract. The butanol and n-hexane fractions showed elevated levels of ALT, AST and ALP as compared to the positive control silymarin. Histopathology showed ∼30% damage to the liver cells with the butanol and n-hexane fractions which still showed some protective activity compared to the CCl₄ treated control. HPLC fingerprinting suggested that hautriwaic acid present in the methanolic extract and its ethyl acetate, and aqueous fractions may be responsible for this hepatoprotective activity of Dodonaea viscosa which was confirmed by in vivo experiments.

N,N′-Bis(4-methoxy­benzyl­idene)-4,4′-(m-phenyl­enedi­oxy)dianiline

Molecules of the title compound, C34H28N2O4, a Schiff base precursor for macrocycles, are located on a mirror plane. The C=N double bond is trans configured. Intermolecular C—H⋯O interactions stabilize the crystal packing.

Supramolecular chemosensor for selective detection of iron in aqueous medium

We have successfully developed a ‘turn-on’ colorimetric chemosensor for Fe3+ based on 1,10-phenanthroline. An amide derivative of 1,10-phenanthroline 4 was developed for the selective recognition of Fe3+ over Co2+, Cr3+, Cu2+, Mn2+, Ni2+, Ag+ and Zn2+ and could measure Fe3+ concentration in the range of 15–210 μM by UV–vis spectroscopy. Moreover, the addition of Fe3+ to a colourless solution of 4 turned its colour to light pink, indicating that 4 is capable of detecting Fe3+ by the naked eye. Compound 4 exhibits a major absorption band centred at 268 which shifted to 278 nm after addition of Fe3+, and a shoulder band around 514 nm was also observed. The complexation of Fe3+ with 4 was analysed at a different pH and favourable binding was observed at pH 6.2.

Hepatoprotective and urease inhibitory activities of garlic conjugated gold nanoparticles

A robust synthetic method is reported for the synthesis of highly stable, poly disperse and spherical gold nanoparticles conjugated to an aqueous garlic extract (G-AuNPs). An ionic solution of gold was mixed and stirred with a dilute aqueous garlic extract at room temperature for 4 hours. The G-AuNPs were characterized by UV-Visible spectroscopy. The morphology and size of the G-AuNPs were determined by atomic force microscopy. FTIR spectroscopy revealed that secondary metabolites present in the garlic extract worked as capping agents around the gold nanoparticles. The G-AuNPs were quite stable even at higher temperature or with salt concentrations up to 10 mM or with various pH ranging from 4 to 11. Two different model systems were tested for evaluating the biological roles of G-AuNPs. They showed excellent hepatoprotective activity in a CCl4-induced acute hepatic injury model which was better than the positive control, silymarin. They also showed urease inhibitory activity with an IC50 value of 180.61 ± 1.06 μg mL−1. Therefore, the G-AuNPs can be useful in the treatment of diseases caused by injury or inflammation.

A novel Salvialactomine from the callus culture of Salvia santolinifolia Boiss

Abstract A novel compound Salvialactomine (1) along with two other unusual occurring natural products Pentatriacontanoic acid 1, 3-dihydroxypropyl ester (2) and 5-Methylflavone (3) were isolated from the callus of Salvia santolinifolia Boiss. Callus was initiated on MS medium containing NAA (0.5 mg/L) and further sub-cultured on MS medium supplemented with NAA with BA (0.5 + 1.5 mg/L). The structures of isolated compounds were determined by using mass spectrometry, 1D, and 2D–NMR techniques. Compounds 1, and 3 were tested for two different cancer cell lines, i.e. Hela (Cervical cancer cell) and PC-3 (Prostate cancer cells). IC50 was found as > 30 using Doxorobicin (0.912 ± 0.12 μmol L−1) as a standard.

Synthesis, characterisation and supramolecular interaction of Rh-biphenylic-imidazole-phenanthroline with antibiotics

A novel rhodium biphenylic imidazole phenanthroline metal-organic complex (BIP-MC) has been synthesised and characterised as a stable supramolecule. The structure of compound was established on the basis ESI, 1H NMR and UV–vis spectroscopic data. The selectivity of BIP-MC as a new fluorescent chemosensor for various antibiotics has been explored. The supramolecular interaction of amoxicillin with BIP-MC enhanced the fluorescence activity of BIP-MC. A linear response of the sensor was observed in the measuring ranges of excitation 240–298 nm and emission 290–360 nm with detection limits of up to 10 μg/ml at an optimum pH 8.0. Based on the observations made here, a new quantitative method for the determination of this drug in synthetic samples without the use of separation of matrix is developed. It is also inferred that the possible fluorescence enhancement is due to the formation of exciplex between the BIP-MC and amoxicillin. These finding will thus help in pharmacokinetics studies of drugs. The sensor was used for the direct assay of amoxicillin antibiotic in commercial pharmaceutical preparations.

2,9-Dichloro-1,10-phenanthroline

The title molecule, C12H6Cl2N2, is almost planar (the r.m.s. deviation of C atoms is 0.04 Å). The C—N and C—C distances indicate delocalization of the π-electrons in the aromatic fused-ring system.