Antileishmanial bioassay guided fractionation of Geosmithia langdonii has resulted in the isolation and identification of two new compounds (1 and 2) together with 10 known compounds (3−12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as mass spectrometry. The absolute configuration at C4, C5, and C6 of 2 was determined as R using a modified Mosher esterification method and NOESY correlations. The extracts and the isolated metabolites were evaluated for their antileishmanial activities. Compounds 3, 9, 11, and 12 were found to be active against Leishmania donovani with IC50 values of 6.9, 3.3, 8.5, and 9.2 μM, respectively, while compounds 1, 5, and 10 showed lower activities against L. donovani with IC50 values of 13.0, 47.3, and 34.0 μM, respectively.

A series of 1-phenyl-3-(4-phenylthiazo-2-yl) urea derivatives 3a-f, 4a-f, and 5a-f have been synthesized to meet the structural requirements essential for anti-inflammatory and antimicrobial properties. Target compounds were synthesized according to a new and convenient strategy. The strategy involves the reaction of 2-amino-4-phenylthiazoles 1a-c with ethyl chloroformate to afford ethyl 4-(substituted)phenylthiazol-2-ylcarbamates 2a-c followed by reaction with the appropriate amines either in a highly boiling point aprotic solvent or solvent free condition. Most of the target compounds showed potent antibacterial activity that equipotent or higher than ampicillin. Also, they were evaluated for their in vivo anti-inflammatory activities in rats compared to indomethacin. Four compounds 3b, 3e, 4e and 5e proved to be the most active anti-inflammatory agents in the present study with superior GI safety profile and good safety margin compared to indomethacin. In abases of molecular modeling; all synthesized 1,3-disubstituted ureas were subjected to docking simulation into active sites of human soluble epoxide hydrolase (sEH).

Cytohesins are small guanine nucleotide exchange factors that stimulate ADP ribosylation factors, Ras-like GTPases, which control various cellular regulatory networks ranging from vesicle trafficking to integrin activation. A small molecule SecinH3 (1,2,4-triazole derivative) in an aptamer displacement assay as a pan-cytohesin Sec7-domain inhibitor was previously identified. Here a series of different SecinH3-analogues was designed and synthesised as potential cytohesin Sec7-domain inhibitors. All final synthesized compounds 6-8, 43-58 and their intermediates were confirmed by 1H NMR, 13C NMR and high resolution Mass. Preliminary biological screening of target compounds indicated that some of the new synthesized secinH3 derivatives showed higher potency and promising activity more than secinH3 itself (unpublished results). Compound 9 and 10 were approximate equal to secinH3 activity as cytohesin antagonist activity. Furthermore compound 52 showed twice inhibition potency if compared to secinH3.

Indirect spectrophotometric method is described for quantification of five of 1,4-dihydropyridine (1,4-DHP) drugs using N-bromosuccinimide (NBS) with the aid of indigo carmine (INC) dye. The method is based on addition of known excess of NBS to an acidified solution of 1,4-DHP drugs and determining the residual of NBS through its ability to bleach the colour of the used dye; the amount of NBS that reacted corresponded to the amount of drugs. Beer’s law is obeyed in the concentration range 1.25–13.00 µg/mL. Good correlation coefficients (0.998-0.999) were found between the absorbance values and the corresponding concentrations. Limits of detections ranged from 0.141 to 0.500 µg/mL. The proposed method was successfully applied to the analysis of dosage forms; percent of recoveries ranged from 97.31 to 99.46% without interference from any common excipients. The statistical comparison by Student’s t-test and variance ratio F-test showed no significant difference between the proposed and official or reported methods.

An investigational study aimed for studying the effect of compritol ATO888 (compritol) on the release of chlorpheniramine maleate (CPM) from hydrophilic matrix (HPMC) was conducted. Matrix tablets were manufactured by direct compression using different compritol - HPMC blends. The release kinetics showed anomalous release mechanism. All the tested matrices containing compritol showed an increase in the release of CPM when compared with tablets contain HPMC only. The results revealed that controlling the speed of water soluble drug CPM release from a hydrophilic polymer HPMC can be obtained through designing a mixed hydrophilic lipophilic matrix using compritol. Compritol showed the ability to affect the water uptake of the matrix. Also, compritol was found to affect the relaxation of HPMC. For matrix containing 50% mixture of HPMC and compritol, the contribution of compritol in 17.5 to 25% of this part will result in a suitable release.

An investigational study aimed for studying the effect of compritol ATO888 (compritol) on the release of chlorpheniramine maleate (CPM) from hydrophilic matrix (HPMC) was conducted. Matrix tablets were manufactured by direct compression using different compritol - HPMC blends. The release kinetics showed anomalous release mechanism. All the tested matrices containing compritol showed an increase in the release of CPM when compared with tablets contain HPMC only. The results revealed that controlling the speed of water soluble drug CPM release from a hydrophilic polymer HPMC can be obtained through designing a mixed hydrophilic lipophilic matrix using compritol. Compritol showed the ability to affect the water uptake of the matrix. Also, compritol was found to affect the relaxation of HPMC. For matrix containing 50% mixture of HPMC and compritol, the contribution of compritol in 17.5 to 25% of this part will result in a suitable release.

Capturing solubility advantages of cocrystals is of great interest, and thus to understand the mechanism by which different excipients could maintain the supersaturation generated by cocrystals at the course of absorption in aqueous media is essential. To achieve this aim, the impact of different excipients on dissolution behavior of indomethacin−saccharin (IND−SAC) were monitored by measuring the concentrations of cocrystal components in the absence and presence of various concentration of excipients by HPLC, and solid phases were analyzed by differential scanning calorimetry after each experiment and the potential of Raman spectroscopy for monitoring phase transformations in situ was tested. No dissolution advantage was offered by cocrystals in the absence of any solution additive. The polymer and surfactant used in the study increased the solubility of IND but not SAC. This differential solubilization effect is believed to have stabilized the cocrystals for a relevant period for the absorption to take place. This could be attributed to either decreased gap between supersaturation and saturation of the drug or drug interaction with the additives. Understanding the effects of excipients type and concentration on the transformation profile is vital for designing enabling formulations for cocrystals. The eutectic constant may be useful in selecting excipients for stabilizing cocrystals.

The present study investigated the bioaccumulation of organochlorines in two milk-producing animals (goats and cows) grazed on the same feed to explore the extent of organochlorines availability in milk and any species effect on the bioaccumulation pattern. Six organochlorine pesticides: aldrin, -endosulfan, -endosulfan, p,p'-DDE, o,p'-DDT and p,p'-DDT were determined in samples collected from four regions in Ethiopia. Aldrin (11.6 µg kg1) was detected only in one cow milk sample and -endosulfan was detected in one goat milk sample at a level of 142.1 µg kg1, and in one cow milk sample (47.8 µg kg1) from the same region. p,p'-DDE was detected in 40% of the milk samples analyzedwhile o,p'-DDT and p,p'-DDT were found in high amounts in almost all samples. The average total DDT (excluding DDD) in the samples was 328.5 µg kg1. Regions known for their malaria epidemics were the most contaminated with DDT residue. The accumulation pattern in both species was not clear under natural sampling.

Two ultraviolet (UV)–spectrodensitometric methods were proposed for the separation and determination of binary and ternary mixtures containing proton pump inhibitors (PPIs). Method A was developed for the assay of omeprazole, panoprazole, rabeprazole, and lansoprazole in binary mixtures with domperidone (DOM) using their isoabsorptive points. Method B was developed for the determination of a ternary mixture containing omeprazole, tinidazole, and clarithromycin. It depends on using malonic acid–acetic anhydride as a spraying reagent to form yellow color (for omeprazole) and dark brown color (for clarithromycin) that are measured at λmax = 350 nm and λmax = 492 nm, respectively, while tinidazole was measured by UV at λmax = 310 nm. For method A, Beer’s law was obeyed for all studied PPIs and domperidone in the concentration range of 180–1440 and 120–720 ng spot−1, respectively. The detection limits for proton pump inhibitors and domperidone were 48.05–73.45 and 30.74–32.50 ng spot−1, respectively, and the quantitation limits were 145.59–222.47 and 93.14–98.48 ng spot−1, respectively. For method B, Beer’s law was obeyed for omeprazole, clarithromycin, and tinidazole in the concentration range of 180–480, 2250–6000, and 30–180 ng spot−1, respectively. The detection limits for omeprazole, clarithromycin, and tinidazole were 20.36, 272.60, and 2.05 ng spot−1, respectively, and the quantitation limits were 61.7, 825.9, and 6.2 ng spot−1, respectively, for the investigated drugs.