Amal Al-Aboudi

Synthesis and antimicrobial activity of cholic acid hydrazone analogues.

Synthesis and antimicrobial activity of cholic acid analogues 4a-t are reported. The synthesis of 4a-t was accomplished from ethylcholate 2. The hydrazone moiety was introduced via coupling of the cholic acid hydrazide (3) with appropriately functionalized aldehyde utilizing acetic acid as a catalyst. Quiet of interest in relation to the synthesized hydrazones is the formation of two rotamers s-cis.E and s-trans.E. Most compounds showed stronger antimicrobial activity against Gram-positive bacteria than Cefaclor and Cefixime. Compounds 4d, 4i and 4j indicated 15-fold stronger antimicrobial activities against Enterobacter faecalis compared to Cefaclor and Cefixime. Some of the synthesized compounds (e.g. 4a, 4c, 4d, 4i, and 4l) reflected two-folds less activity against Escherichia coli relative to Cefixime.

Plants used for the treatment of diabetes in Jordan: A review of scientific evidence

Context: Diabetes is a serious disease which has reached epidemic proportions in many parts of the world. Despite the tremendous developments in medicinal chemistry, traditional medicine is still a common practice for the treatment of diabetes. Objectives: In Jordanian traditional medicine, 69 plant species are used by diabetic patients to reduce glucose levels in blood. The aim of the present study is to report these plants and link their traditional use with scientific evidence confirming their claimed activity. The plant part(s) used, method(s) of preparation, common Arabic names, and other ethnopharmacological uses are also listed. Materials and methods: The literature and databases (SciFinder, PubMed, ScienceDirect and Scirus) have been thoroughly investigated and the plants used have been grouped according to the reported scientific evidence. Results: Results showed that 40 plants have been reported to possess hypoglycemic activities in in vivo/in vitro experiments. Five plant species did not exhibit in vivo hypoglycemic activity, while 24 plants had not been studied for such an activity. Twenty plants had been screened for their α-amylase/α-glucosidase inhibitory activities. Discussion: The reported in vivo and in vitro hypoglycemic as well as α-amylase/α-glucosidase inhibitory activities of these plants are discussed. Conclusion: Additional in vitro and in vivo studies are needed to test the hypoglycemic activity of the plants with claimed antidiabetic activity which has not yet been evaluated. Identification of the active ingredients of potent plants might generate lead compounds in drug discovery and development.

New oxandrolone derivatives by biotransformation using Rhizopus stolonifer

Structural transformation of the steroidal lactone, oxandrolone (1), by suspended-cell cultures of the plant pathogen fungus Rhizopus stolonifer, resulted in the production of three new metabolites. These metabolites were identified as 11alpha-hydroxyoxandrolone (2), 6alpha-hydroxyoxandrolone (3) and 9alpha-hydroxyoxandrolone (4), by different spectroscopic methods and single-crystal X-ray diffraction analysis for metabolite 2. Compounds 1 and 3 showed a significant beta-glucuronidase inhibitory activity.

Microbial transformation of testosterone by Rhizopus stolonifer and Fusarium lini.

The microbial transformation of testosterone by the fungi Rhizopus stolonifer and Fusarium lini has been investigated for the first time. The bioconversion reactions observed from R. stolonifer included oxidation of a 17β-hydroxyl group, a hydroxylation at equatorial 11α position, reduction of the double bond at C-4 with oxidation of the methylene at C-6 to the corresponding keto group, and lactonisation of ring D; the latter is the first report of this reaction by a Rhizopus species. Fusarium lini promoted 1-dehydrogenation of the steroid, which has been rarely observed in fungi cultures. The other routes of biotransformations included oxidation of the 17β-hydroxyl group and the hydroxylation at 11α position. These reactions are not common for Fusarium species.

Biotransformation of methyl cholate by Aspergillus niger.

Biotransformation of methyl cholate using Aspergillus niger was investigated. This led to the isolation of two derivatives: methyl 3alpha,7alpha,12alpha,15beta-tetrahydroxy-5beta-cholan-24-oate identified as a new compound, and a known compound methyl 3alpha,12alpha-dihydroxy-7-oxo-5beta-cholan-24-oate. The structure elucidation of the new compound was achieved using 1D and 2D NMR, MS and X-ray diffraction.

Three new seco-ursadiene triterpenoids from Salvia syriaca.

Three new seco-ursadiene triterpenoids 1–3 together with 11 known compounds were isolated from Salvia syriaca of Jordanian origin. The compounds were identified by using NMR spectroscopy including extensive 2D NMR experiments and mass spectrometry. The structure of compound 3 was confirmed by X-ray crystallography, and the information thus obtained was used to confirm the stereochemistry of compounds 1 and 2. This is the second report of 17,22-seco-17(28),12-ursadien-22-oic acids.

Selective phytotoxic activity of 2,3,11β,13-tetrahydroaromaticin and ilicic acid isolated from Inula graveolens

Inula graveolens is a poisonous annual plant of Mediterranean origin. The invasive nature of the plant suggests that it may possess phytotoxic activity. The aim of this study was to assess the ability of I. graveolens to inhibit the growth of different plants in Petri dish and to identify the main bioactive compounds. Bio-guided fractionation of the plant extracts led to the isolation of 2,3,11β,13-tetrahydroaromaticin (THA) and ilicic acid. Both compounds showed selective and significant phytotoxic activity at 25 ppm. Root length of barley, oat, millet, tuberous canary grass and lentils were significantly reduced by 25 ppm of THA, while the root of cauliflower, cress and radish were similarly reduced by ilicic acid at 25 ppm. The structure of each compound was elucidated by using NMR and HR-MS. X-ray crystallography of THA is reported for the first time to confirm the relative stereochemistry of the compound.

Synthesis and Antibacterial Activity of Some Novel 4-Oxopyrido(2,3-a)phenothiazines

A series of substituted 4‐oxopyrido[2,3‐a]phenothiazine‐3‐carboxylic acids (6a–d) were prepared via cyclization of the corresponding ethyl 7‐(arylthioxy)‐8‐nitro(or azido)‐4‐oxoquinoline‐3‐carboxylates (3a–d/4a–d), followed by hydrolysis of the resultant esters (5a–d). Among these tetracyclics, compound 6a with unsubstituted terminal benzo‐ring D was the most active against representative Gram‐positive and Gram‐negative bacterial strains. These compounds were also active against methicillin‐resistant Staphylococcus aureus (MRSA), with very low toxicity to normal cells. Virtual screening using ligand–protein docking modeling predicted that the compounds 6a–d are potential inhibitors of the topoisomerase IV enzyme and that hydrophobic interactions and hydrogen bonds are the major molecular interactions between these compounds and the residues of the active site of topoisomerase IV.

In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes

Aim:To investigate the binding mode of synthesized adamantly derivatives inside of cholinesterase enzymes using molecular docking simulations.Methods:A series of hybrid compounds containing adamantane and hydrazide moieties was designed and synthesized. Their inhibitory activities against acetylcholinesterase (AChE) and (butyrylcholinesterase) BChE were assessed in vitro. The binding mode of the compounds inside cholinesterase enzymes was investigated using Surflex-Dock package of Sybyl7.3 software.Results:A total of 26 adamantyl derivatives were synthesized. Among them, adamantane-1-carboxylic acid hydrazide had an almost equal inhibitory activity towards both enzymes, whereas 10 other compounds exhibited moderate inhibitory activity against BChE. The molecular docking studies demonstrated that hydrophobic interactions between the compounds and their surrounding residues in the active site played predominant roles, while hydrophilic interactions were also found. When the compounds were docked inside each enzyme, they exhibited stronger interactions with BChE over AChE, possibly due to the larger active site of BChE. The binding affinities of the compounds for BChE and AChE estimated were in agreement with the experimental data.Conclusion:The new adamantly derivatives selectively inhibit BChE with respect to AChE, thus making them good candidates for testing the hypothesis that BChE inhibitors would be more efficient and better tolerated than AChE inhibitors in the treatment of Alzheimers disease.

Butyrylcholinesterase inhibitory activity of testosterone and some of its metabolites

Testosterone and ten of its metabolites were examined as inhibitors of butyrylcholinesterase. A significant enzyme inhibition activity (IC50 = 1.55 μM) was observed for androst-4-en-3,7-dione. The kinetic parameters of butyrylcholinesterase inhibition were determined and molecular docking was carried out in order to develop a better understanding of the inhibitor-enzyme interactions. The results showed that the inhibition was non-competitive, stabilized mainly by hydrogen bonds and hydrophobic interactions between the inhibitor and butyrylcholinesterase.