Glioblastoma multiforme (GBM) is the most common and lethal primary intracranial tumor in humans. Monotherapeutic interventions have not been successful. The objective of the current studies was to establish the effective combination therapy consisting of pifitrin as a sensitizer, and curcumin as therapeutic incorporated into miktoarm micelles. A2B type miktoarm stars were prepared using a combination of click chemistry with ring opening polymerization on a core with orthogonal functionalities. These self-assemble into spherical micelles with hydrophobic core and hydrophilic corona structure. Micellar delivery systems for curcumin based on these miktoarm star polymers were prepared, characterized and tested on cultures sensitized with pifitrin. The results show that: (1) pifitrin and temozolamide in combination with curcumin cause significant cell death compared with the individual therapeutics (incorporated or not in micelles), and (2) repeated exposure to the same treatments is necessary to fully prevent a re-growth of glioblastoma cells both in 2D and 3D cultures. Although the incorporation of curcumin into A2B star polymer micelles did not increase the extent of cell death compared with curcumin alone, the advantage of micelles is that they significantly increase the aqueous solubility of curcumin and sustain its release; this will likely reduce the frequency of its administration required to be effective in vivo. A2B miktoarm polymers could be a new viable delivery system for curcumin and other anticancer drugs with similar limitations.

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.

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.

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.