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.

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.