Saima Jalil

3-Formylchromones: Potential antiinflammatory agents

The synthesis and characterization of 3-formylchromone (1) and its derivatives 2-24 and evaluation of their potential antiinflammatory activities is reported here. These compounds were characterized by (1)H NMR, EI MS, IR, and UV spectroscopic techniques and elemental analysis. The synthesized compounds were evaluated by using various in vitro and in vivo assay models for antiinflammatory activity and their effects were compared with known standard drug such as aspirin and indomethacin. Among all tested compounds, 1, 2, 5, 6, 9, 14, 16-19, 21-23, showed promising antiinflammatory activities. The results and SAR has been discussed in this report.

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

1,3,4-Oxadiazole-2(3H)-thione and its analogues: a new class of non-competitive nucleotide pyrophosphatases/phosphodiesterases 1 inhibitors.

A series of 1,3,4-oxadiazole-2 (3H)-thiones and 1,3,4-thiadiazole-2 (3H)-thiones were synthesized and evaluated for their inhibitory activities against the two nucleotide pyrophosphatase phosphodiesterase 1 enzymes. Dixon, as well as Lineweaver-Burk plots, and their secondary replots have indicated that the inhibition was of pure non-competitive type, against both snake venom and pure human recombinant enzymes as the V(max) values decreases without affecting the K(m) values. 5-[4-(t-Butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2 (3H)-thione (17) and [4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2 (3H)-thione (1) were found to be the most active compounds with IC(50) values 66.47 and 368microM, respectively. The K(i) values were 100microM and 360microM against the snake venom and human recombinant NPP1 enzyme, respectively. Most active compounds were found to be non-toxic in neutrophil viability assay.

Synthesis and anti-inflammatory activity of some selected aminothiophene analogs

Some 2-aminothiophene analogs 1–6 were synthesized and characterized. Among the tested compounds, compound 1 (IC50 121.47 μM) exhibited highest while the compound 5 showed least anti-inflammatory potential (IC50 422 μM).

Fungal transformation of dydrogesterone and inhibitory effect of its metabolites on the respiratory burst in human neutrophils.

The biotransformation of the synthetic hormone dydrogesterone (1) by a number of fungal strains – including Cephalosporium aphidicola, Rhizopus stolonifer, Cunninghamella elegans, and Fusarium lini – afforded ten different metabolites, compounds 2–11. From a structural point of view, these transformations involved a combination of hydroxylation, oxidation, reduction, and/or epoxidation. The pregnane‐based metabolites 10 and 11 are new compounds. All the known compounds were obtained for the first time from 1 by fungal transformation. The metabolites 3, 5, and 8 showed more‐potent respiratory‐burst inhibitory activity than the substrate 1 in a neutrophil‐based cellular assay (Table 3).

Inhibitory effect of lactone fractions and individual components from three species of the Achillea millefolium complex of Bulgarian origin on the human neutrophils respiratory burst activity

Achillea species are widely used in folk medicine for treatment of inflammatory diseases. The inhibitory effect on the human neutrophils respiratory burst activity of total extracts, their fractions and some main constituents of the flower heads from Achillea asplenifolia, A. collina and A. distans belonging to A. millefolium complex of Bulgarian origin, were tested by the modified method of Tan and Berridge. Seven from the investigated fractions showed activity similar or higher than that of indomethacine and might be evaluated as nonsteroidal anti-inflammatory agents.

Structural Basis of Binding and Rationale for the Potent Urease Inhibitory Activity of Biscoumarins

Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and reactive cysteine residue in the active sites. In the current study we examined a series of biscoumarins 1–10 for their mechanisms of inhibition with the nickel containing active sites of Jack bean and Bacillus pasteurii ureases. All these compounds competitively inhibited Jack bean urease through interaction with the nickel metallocentre, as deduced from Michaelis-Menten kinetics, UV-visible absorbance spectroscopic, and molecular docking simulation studies. Some of the compounds behaved differently in case of Bacillus pasteurii urease. We conducted the enzyme kinetics, UV-visible spectroscopy, and molecular docking results in terms of the known protein structure of the enzyme. We also evaluated possible molecular interpretations for the site of biscoumarins binding and found that phenyl ring is the major active pharmacophore. The excellent in vitro potency and selectivity profile of the several compounds described combined with their nontoxicity against the human cells and plants suggest that these compounds may represent a viable lead series for the treatment of urease associated problems.

Hepatoprotection by chemical constituents of the marine brown alga Spatoglossum variabile: A relation to free radical scavenging potential

Context: In the course of searching hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine brown alga Spatoglossum variabile Figaro et DE Notar (Dictyoaceae) against CCl4-induced liver damage in Wistar rats was investigated. The compounds were first investigated for in vitro radical scavenging potential and were also tested for β-glucuronidase inhibition to further explore the relationship between hepatoprotection and antiradical potential. Methods: The compounds cinnamic acid esters 1 and 2 and aurone derivatives 3 and 4 were first investigated for in vitro radical scavenging potential against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and superoxide anion radicals. In vivo hepatoprotective studies were performed in seven groups (n = 6) of Wistar rats. The test groups were pretreated with compounds (10 mg/kg body weight, po) orally for 30 min before the intraperitoneal administration of a dose of 20% CCl4 diluted with dietary cooking oil. Moreover, compounds were also tested for β-glucuronidase inhibition to explore the relationship between hepatoprotection and radical scavenging potential. Results: The test compounds 1–4 were found to exhibit antiradical activity against 1,1-diphenyl-2-picrylhydrazyl radicals with IC50 values ranging between 54 and 138 µM, whereas aurone derivatives 3 and 4 additionally exhibited superoxide anion scavenging effects with IC50 values of 95 and 87 µM, respectively. In addition, these compounds were found to be weak inhibitors of xanthine oxidase (IC50 ≥1000 µM). In animal model, pretreatment with compounds 2–4 significantly blocked the CCl4-induced increase in the levels of the serum biochemical markers. Conclusion: It appears that the hepatoprotection afforded by these compounds was mainly due to their radical scavenging activity that protected the cells from the free radicals generated by CCl4-induced hepatotoxicity.