Synthesis and Biological Evaluation of Octahydroquinazolinones as Phospholipase A2, and Protease Inhibitors: Experimental and Theoretical Exploration.

Phospholipase A2 (PLA2) promotes inflammation via lipid mediators and releases arachidonic acid (AA), and these enzymes have been found to be elevated in a variety of diseases, including rheumatoid arthritis, sepsis, and atherosclerosis. The mobilization of AA by PLA2 and subsequent synthesis of prostaglandins are regarded as critical events in inflammation. Inflammatory processes may be treated with drugs that inhibit PLA2, thereby blocking the COX and LOX pathways in the AA cascade. To address this issue, we report herein an efficient method for the synthesis of a series of octahydroquinazolinone compounds (4a-h) in the presence of the catalyst Pd-HPW/SiO2 and their phospholipase A2, as well as protease inhibitory activities. Among eight compounds, two of them exhibited overwhelming results against PLA2 and protease. By using FT-IR, Raman, NMR, and mass spectroscopy, two novel compounds were thoroughly studied. After carefully examining the SAR of the investigated compounds against these enzymes, it was found that compounds (4a, 4b) containing both electron-donating and electron-withdrawing groups on the phenyl ring exhibited higher activity than compounds with only one of these groups. DFT studies were employed to study the electronic nature and reactivity properties of the molecules by optimizing at the BLYP/cc-pVDZ. Natural bond orbitals helped to study the various electron delocalizations in the molecules, and the frontier molecular orbitals helped with the reactivity and stability parameters. The nature and extent of the expressed biological activity of the molecule were studied using molecular docking with human non-pancreatic secretory phospholipase A2 (hnps-PLA2) (PDB ID: 1DB4) and protease K (PDB ID: 2PWB). The drug-ability of the molecule has been tested using ADMET, and pharmacodynamics data have been extracted. Both the compounds qualify for ADME properties and follow Lipinski's rule of five.

An Improved Synthesis of Key Intermediate to the Formation of Selected Indolin-2-Ones Derivatives Incorporating Ultrasound and Deep Eutectic Solvent (DES) Blend of Techniques, for Some Biological Activities and Molecular Docking Studies.

We have developed a new idea to synthesize a key intermediate molecule by utilizing deep eutectic solvent (DES) and ultrasound in a multistep reaction to ensure process cost-effectiveness. To confirm the stability of reagents with DES, electronic energies were calculated at the B3LYP/6-31+G(d,p) level of theory. DES stabilized the reagents mainly due to strong intermolecular hydrogen bonding. Key intermediate (3) and final compounds (4a-n) were synthesized in a higher yield of 95% and 80%-88%, respectively. Further, final compounds (4a-n) were assessed for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation. The compounds 4f, 4g, 4j, 4l, and 4m showed good anti-inflammatory activity, while 4f, 4i, and 4n exhibited very good analgesic activity as compared to the standard drug. The ulcerogenicity of selected compounds was far less than the indomethacin. The ligands had also shown a good docking score (4f = -6.859 kcal/mol and 4n = -7.077 kcal/mol) as compared to control indomethacin (-6.109 kcal/mol) against the target protein COX-2. These derivatives have the potential to block this enzyme and can be used as NSAID. The state-of-art DFT theory was used to validate the lipid peroxidation mechanism of the active compounds which was in good agreement with the variations of BDEs and IP of the tested compounds.

Ultrasound-assisted extraction of some branded tea: Optimization based on polyphenol content, antioxidant potential and thermodynamic study.

Tea is one of the top beverages used around the world every day, which contains a high amount of polyphenols and antioxidants. The main aim of this research is to quantify some marketed black tea (Rabea, Lipton, Alkbous, Green gold and Haritham) for phenolic contents and antioxidant potential evaluation by ultrasound solvent extraction and was compared with conventional extraction. Ultrasonic extraction was optimized by considering frequencies (26 kHz, 40 kHz), temperature (30, 40 and 50 °C), and power (30, 40 and 50%) at a fixed time of 30 min. In both the ultrasonic frequencies, 40 °C temperature and 40% power combination exhibited highest cumulative yield (mg/100 g DW), total phenolic content (mg gallic acid/g DW), flavonoids (mg/g DW) and DPPH radical scavenging activity (%) in all branded tea. Within each brand of tea, at any temperature-power combination at particular frequency results were not significantly different. But, at a similar condition of temperature power results were found significantly different between two frequencies. Furthermore, ultrasonic extraction process was analyzed thermodynamically by selecting some basic parameters. Thermodynamics results showed the extraction process was feasible, spontaneous and irreversible. Also, 26 kHz ultrasonic probe is more appropriate for the extraction purpose and thermodynamically more acceptable as compared to 40 kHz ultrasonic bath. Moreover, Haritham was selected as the best tea brand due to its high polyphenol contents and antioxidant potential.