SAR based in-vitro anticholinesterase and molecular docking studies of nitrogenous progesterone derivatives.

Progesterone is a steroidal hormone that has been described with pathogenic features of brain dysfunction, realized with advanced age-related neurodegenerative diseases such as Alzheimer's disease. In this study, sixteen nitrogenous derivatives of progesterone which we previously synthesized have been used for Alzheimer targets. The progesterone derivatives (1-16) were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials in a dose-dependent manner. All the compounds exhibited overwhelming AChE inhibitions, with IC50 values ranging from 14.40 to 40.37 µM. Similarly, the BChE inhibitory potentials of our compounds were also dominant with IC50values between 20.08 and 46.84 µM. In comparison to our compounds, the standard drug galantamine attain IC50 values of 12.03 and 18.20 µM against AChE and BChE respectively. Molecular docking studies suggested that the compounds exerted their inhibitory activity by binding to the active site of the enzyme. The cholinergic system plays an important role in the regulation of learning and memory processes and has been a major target for the design of anti-Alzheimer's drugs. Therefore, these nitrogen-containing progesterone derivatives will be of potential interest to researchers working in AD for developing new drugs or chemical tools to study the disease.

Synthesis, pharmacological evaluation and docking studies of progesterone and testosterone derivatives as anticancer agents.

Steroidal hormones progesterone and testosterone play a vital role in breast and prostate cancers. In this research, we have synthesized and characterized a total of thirty-one (31) new nitrogenous derivatives of progesterone and testosterone. The synthesized derivatives (1-31) were screened for their anti-cancer potential against MCF-7 and PC-3 cell lines of breast using MTT assay. The compounds 1-31exhibited significant inhibitory potentials against MCF-7 and PC-3 cell lines. In MCF-7 assay, compound 17 displayed IC50 value of 04 ±â€¯0.02 µM while compound 18 was leading in PC-3 assay with IC50 of 03.14 ±â€¯0.4 µM. Tamoxifen was used as positive control which exhibited an IC50of 0.12 ±â€¯0.03 and 0.26 ±â€¯0.01 µM against MCF-7 and PC-3 respectively. The compounds also showed good anti-inflammatory activity according to oxidative burst inhibition by chemiluminescence technique where ibuprofen was used as positive control with 73.2 ±â€¯1.4% ROS inhibition. The compounds showed the percent ROS inhibition between 23.2 ±â€¯0.2 and -3.2 ±â€¯4.1. The results of the compounds were compared with the positive control ibuprofen. Molecular docking correlations suggest that the compounds exerted their inhibitory activity by binding to the active of the enzyme.

Purification and characterization of 2S albumin from Nelumbo nucifera.

The 2S albumins are a group of seed storage proteins that have recently attracted considerable attention in the field of allergen science due to their allergenic potential. A new 2S albumin from seeds of Nelumbo nucifera (Nn-2S alb) was purified to electrophoretic homogeneity by the combination of ammonium sulfate fractionation, gel filtration, and ion exchange chromatography. The protein has a molecular mass of about 12 kDa estimated by SDS-PAGE, in good agreement with 12.5 ± 0.01 kDa determined by ESI-MS. Circular dichroism data showed that protein contained about 66% α-helices as estimated by K2D3, indicating that the protein was predominantly helical. The sedimentation coefficient (s°20,w) of the predicted model was 1.72 ± 0.21 S. The predicted 3-dimensional structure of the Nn-2S alb revealed that the protein has a region of 12 amino acids which largely corresponds to the conserved immuno-dominant epitope of 2S allergens.

Purification and biochemical properties of SDS-stable low molecular weight alkaline serine protease from Citrullus colocynthis.

A low molecular weight serine protease from seeds of Citrullus colocynthis was purified to electrophoretic homogeneity with high level of catalytic efficiency (22,945 M(-1) S(-1)). The enzyme was a monomer with molecular mass of 25 kDa estimated by SDS-PAGE. The enzyme was highly active over a pH range of 6.5-9.0 and temperature range of 20-80 °C, with maximum activity at pH 7.5 and at 50 °C. The K(m) and K(cat) were 73 µg/mL and 67/s, respectively. The enzyme was strongly inhibited by PMSF, moderately by soybean trypsin inhibitor, indicating that the enzyme was a serine protease. The enzyme retained 86 and 73% of its activity in the presence of urea and DTT, respectively, and its activity was slightly enhanced in the presence of anionic detergent (SDS). Thus, the enzyme is a novel SDS-stable protease with high catalytic efficiency over wide ranges of pH and temperature which is commercially promising for various industrial applications.

Antioxidant, cholinesterase inhibition activities and essential oil analysis of Nelumbo nucifera seeds.

Nelumbo nucifera seeds' essential oil (EO), crude extract and subsequent fractions were evaluated for their DPPH, ABTS and superoxide anion-free radical scavenging and cholinesterase inhibitory activities. The ethyl acetate fraction and EO showed outstanding antioxidant activities with IC50 values of 191, 450 µg/mL (DPPH), 123, 221 µg/mL (ABTS) and 69, 370 µg/mL (superoxide anion). The ethyl acetate fraction and EO also caused significant inhibition of acetylcholinesterase and butyrylcholinesterase with IC50 values of 70 ± 0.6, 64 ± 0.8 and 75 ± 0.3, 58 ± 0.2, in dose-dependent manner. The first ever gas chromatography-mass spectrometry analysis of the EO obtained from N. nucifera seeds resulted in identification of 19 constituents, mainly comprised of oxygenated sesquiterpenes responsible for their promising bioactivity. The crude and fractions revealed the presence of saponins, flavonoids, steroids, alkaloids, terpenoids and cardiac glycosides in phytochemical investigation.

Antibacterial, antifungal, antispasmodic and Ca++ antagonist effects of Caesalpinia bonducella.

Caesalpinia bonducella F. (Leguminosae) has been used as a folk medicine for a variety of ailments. The crude extract of C. bonducella and its fractions were studied for antibacterial, antifungal, antispasmodic and Ca++ antagonistic properties. The strongest antibacterial effect was displayed by the n-butanol (72%) and ethyl acetate (80%) fractions, followed by the crude extract (46% and 42%), against Escherichia coli and Bacillus subtilis, respectively. The plant extract and its fractions showed mild to excellent activity in antifungal bioassays, with maximum antifungal activity against Candida glaberata (80%) and Aspergillus flavus (70%) by the n-butanol and chloroform fractions, followed by the crude extract (70% and 65%). Caesalpinia bonducella extract caused concentration-dependent inhibition of spontaneous and high K+ (80 mM)-induced contractions of isolated rabbit jejunum preparations, similar to that caused by Verapamil. These results indicate that C. bonducella exhibits antibacterial, antifungal, spasmolytic and Ca++ channel blocking actions.

Purification and biochemical characterization of alkaline serine protease from Caesalpinia bonducella.

A high molecular weight serine protease has been purified to electrophoretic homogeneity from the seeds of Caesalpinia bonducella Flem. (Caesalpiniaceae) by the combination of size exclusion and ion exchange chromatography. About 524 fold purification was achieved with an overall recovery of 6.8%. The specific activity was found to be 86 U/mg/min at pH 8.0. The calculated K(m) and V(max) were 1.66 mg/mL and 496.68 units/min per mg of protein, respectively. The molecular mass was estimated to be about 63 kDa by sodium dodecyl sulfate PAGE. The enzyme showed optimum activity at pH 8.0 and exhibited its highest activity at 40 degrees C. The enzyme was strongly inhibited by 2mM phenylmethylsulfonyl fluoride (PMSF), suggesting the presence of a serine residue at the active site. PMSF showed a pure competitive type of inhibition with the serine protease enzyme. It was observed that enzyme activity was enhanced in the presence of dications and was active against a variety of modified substrates and natural proteins.