The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers.

Hydroxy vasntine (1), a new pyrroloquinazoline alkaloidsalong with two known compounds: 7-hydroxy vasicine (2) and 7-hydroxy vasicine (3) were isolated from the aerial parts of Anisotes trisulcus (Forssk) Nees (Acanthaceae). Their structures were established by UV, IR, ID NMR, in addition to mass spectroscopic data and comparison with literature data. The different fractions were evaluated for their cytotoxic activity using the brine shrimp bioassay.

Hydroxy vasntine (1), a new pyrroloquinazoline alkaloidsalong with two known compounds: 7-hydroxy vasicine (2) and 7-hydroxy vasicine (3) were isolated from the aerial parts of Anisotes trisulcus (Forssk) Nees (Acanthaceae). Their structures were established by UV, IR, ID NMR, in addition to mass spectroscopic data and comparison with literature data. The different fractions were evaluated for their cytotoxic activity using the brine shrimp bioassay.

Hydroxy vasntine (1), a new pyrroloquinazoline alkaloidsalong with two known compounds: 7-hydroxy vasicine (2) and 7-hydroxy vasicine (3) were isolated from the aerial parts of Anisotes trisulcus (Forssk) Nees (Acanthaceae). Their structures were established by UV, IR, ID NMR, in addition to mass spectroscopic data and comparison with literature data. The different fractions were evaluated for their cytotoxic activity using the brine shrimp bioassay.

The purpose of this study was to develop pluronic-based in situ gelling formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed at prolonging the residence time, controlling drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance. The in situ gel formulations were prepared using different concentrations of pluronic F-127 (PF-127) alone and in combination with pluronic F-68 (PF-68). The prepared formulations were evaluated for their gelation temperature (Tgel), in vitro drug release, rheological properties, mucoadhesion properties and tolerability by vaginal mucosa in tissue levels. The Tgel decreased with increasing PF-127 concentration. The Tgel was modulated by addition of PF-68 to be within the acceptable range of 25-37°C. With increasing pluronic concentration, the in-vitro drug release decreased, viscosity and mucoadhesive force increased. Histopathological examination of rabbit vaginas from the control and treated groups revealed normal histology of the vagina and cervix. Based on the in-vitro evaluation of prepared formulations, the in situ gelling liquid formulated with PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation.

The purpose of this study was to develop pluronic-based in situ gelling formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed at prolonging the residence time, controlling drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance. The in situ gel formulations were prepared using different concentrations of pluronic F-127 (PF-127) alone and in combination with pluronic F-68 (PF-68). The prepared formulations were evaluated for their gelation temperature (Tgel), in vitro drug release, rheological properties, mucoadhesion properties and tolerability by vaginal mucosa in tissue levels. The Tgel decreased with increasing PF-127 concentration. The Tgel was modulated by addition of PF-68 to be within the acceptable range of 25-37°C. With increasing pluronic concentration, the in-vitro drug release decreased, viscosity and mucoadhesive force increased. Histopathological examination of rabbit vaginas from the control and treated groups revealed normal histology of the vagina and cervix. Based on the in-vitro evaluation of prepared formulations, the in situ gelling liquid formulated with PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation.

The purpose of this study was to develop pluronic-based in situ gelling formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed at prolonging the residence time, controlling drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance. The in situ gel formulations were prepared using different concentrations of pluronic F-127 (PF-127) alone and in combination with pluronic F-68 (PF-68). The prepared formulations were evaluated for their gelation temperature (Tgel), in vitro drug release, rheological properties, mucoadhesion properties and tolerability by vaginal mucosa in tissue levels. The Tgel decreased with increasing PF-127 concentration. The Tgel was modulated by addition of PF-68 to be within the acceptable range of 25-37°C. With increasing pluronic concentration, the in-vitro drug release decreased, viscosity and mucoadhesive force increased. Histopathological examination of rabbit vaginas from the control and treated groups revealed normal histology of the vagina and cervix. Based on the in-vitro evaluation of prepared formulations, the in situ gelling liquid formulated with PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation.

The purpose of this study was to develop pluronic-based in situ gelling formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed at prolonging the residence time, controlling drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance. The in situ gel formulations were prepared using different concentrations of pluronic F-127 (PF-127) alone and in combination with pluronic F-68 (PF-68). The prepared formulations were evaluated for their gelation temperature (Tgel), in vitro drug release, rheological properties, mucoadhesion properties and tolerability by vaginal mucosa in tissue levels. The Tgel decreased with increasing PF-127 concentration. The Tgel was modulated by addition of PF-68 to be within the acceptable range of 25-37°C. With increasing pluronic concentration, the in-vitro drug release decreased, viscosity and mucoadhesive force increased. Histopathological examination of rabbit vaginas from the control and treated groups revealed normal histology of the vagina and cervix. Based on the in-vitro evaluation of prepared formulations, the in situ gelling liquid formulated with PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation.

To enhance the activity of amantadine against HCV, its amide prodrugs with thiazolidine-4-carboxylic acid derivatives (6-9) and bile acids (10 and 11) were designed and synthesized. In vitro kinetic stability of amide prodrugs 8 and 10 were investigated in aqueous buffer solution with variable pH values (1.2, 4.5. 6.8, 7.4. 8.0) and in biological fluids of 90% human plasma and rat liver homogenate at 37°C. In vivo release of the parent drug from these prodrug was investigated in mice with the thioazolidine-4-carboxylic acid amide 8 as representative of these delivery systems. Results from the in vivo distribution study indicated that the level of amantadine increased significantly in liver from 8 when compared to amantadine itself. The study suggested the synthesized delivery systems is promising carrier to enhance the hepatic bioavailability of amantadine.

To enhance the activity of amantadine against HCV, its amide prodrugs with thiazolidine-4-carboxylic acid derivatives (6-9) and bile acids (10 and 11) were designed and synthesized. In vitro kinetic stability of amide prodrugs 8 and 10 were investigated in aqueous buffer solution with variable pH values (1.2, 4.5. 6.8, 7.4. 8.0) and in biological fluids of 90% human plasma and rat liver homogenate at 37°C. In vivo release of the parent drug from these prodrug was investigated in mice with the thioazolidine-4-carboxylic acid amide 8 as representative of these delivery systems. Results from the in vivo distribution study indicated that the level of amantadine increased significantly in liver from 8 when compared to amantadine itself. The study suggested the synthesized delivery systems is promising carrier to enhance the hepatic bioavailability of amantadine.