Benzothiazole incorporated thiazolidin-4-ones and azetidin-2-ones derivatives: Synthesis and in vitro antimicrobial evaluation

In this study, a series of novel thiazolidin-4-ones (5a–g) and azetidin-2-ones (6a–g) were synthesized from N-(6-chlorobenzo[d]thiazol-2-yl)hydrazine carboxamide derivatives of the benzothiazole class. Antimicrobial properties of the title compound derivatives were investigated against one Gram (+) bacteria (Staphylococcus aureus), three Gram (−) bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and five fungi (Candida albicans, Aspergillus niger, Aspergillus flavus, Monascus purpureus and Penicillium citrinum) using serial plate dilution method. The investigation of antibacterial and antifungal screening data revealed that all the tested compounds showed moderate to good inhibition at 12.5–200 μg/mL in DMSO. It has been observed that azetidin-2-ones derivatives are found to be more active than thiazolidin-4-ones derivatives against all pathogenic bacterial and fungal strains

Discovery of novel isonipecotic acid-based heteroaryl amino acid derivatives as potential anticonvulsant agents: Design, synthesis, in-silico ADME study, and molecular docking studies

Background: Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsions, and odd behavior. Several substituted-(naphthalen-2-yl)-3-(1H-indol-3-yl) allyl)-1,4-dihydropyridine-4-carboxylic acid derivatives (5a-j) were intended to be produced in the current research effort to reduce convulsions and seizures. Materials and Methods: The newly developed compounds were produced by the prescribed process. Numerous methods (infrared spectroscopy (IR), nuclear magnetic resonance (NMR), mass, elemental analysis, etc.) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed absorption, distribution, metabolism, and excretion (ADME) predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the gamma amino butyric acid (GABA)-A target protein. Results: Anticonvulsant screening results identified compounds 5f, 5h, 5d, and 5b as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with LEU B: 99, TYR A: 62, Ala A: 174, and THR B: 202, and the outcomes were good and in agreement with in vivo findings. Conclusions: The study's findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogs may therefore represent a possible lead, and additional studies may result in a potential new drug candidate

Box-Behnken Design (BBD) Application for Optimization of Chromatographic Conditions in RP-HPLC Method Development for the Estimation of Thymoquinone in Nigella sativa Seed Powder

Thymoquinone (THY) is a bioactive compound present in the seed powder of Nigella sativa (NS). This research aims to precisely and accurately estimate THY using high-performance liquid chromatography (HPLC) with a Quality by Design (QbD) application. Box-Behnken design (BBD) was employed to optimize the chromatographic conditions for HPLC method development, taking mobile phase flow rate, pH of the buffer, and λmax as independent variables and retention time and tailing factor as the measured responses. The mobile phase composition was methanol: acetonitrile: buffer (2.2 mM ammonium formate) at the ratio of 35:50:15 v/v/v on a Symmetry® C18 (5 μm, 3.9 × 150 mm) column. In isocratic mode, it had a flow rate 0.9 mL min−1 and eluted analyte was detected at 249 nm. Validation parameters followed the International Council for Harmonization (ICH) guidelines for the new HPLC method. The method was linear over the range 6.25–100 µg mL−1 with a coefficient of determination (r2) of 0.9957. The limit of detection (LOD) and limit of quantification (LOQ) were 2.05 and 6.25 µg mL−1, respectively. The %RSD of system suitability for retention time was 1.42% and for the tailing factor it was 0.695%. In addition, the developed method was precise, accurate, and robust according to ICH criteria. The developed HPLC method is simple, accurate, quick, and robust, and it could be used for the routine analysis of THY in different kinds of formulations

In vitro release and cytotoxicity study of encapsulated sulfasalazine within LTSP micellar/liposomal and TSP micellar/niosomal nano-formulations

The micelles/liposome formulation for the first time has been constructed via thin-film hydration method containing soy lecithin (L), tween 80 (T), squalene (S), and polyvinyl alcohol (P) (LTSP nanoparticles). Similar ingredients except for lecithin were used for preparing micellar/niosomal vesicular SSZ nanoformulation (TSP nanoparticles). The percent drug loading and encapsulation efficiency of SSZ was 7.39 and 98.5 ± 0.3 for the 7.5:100 (w/w) ratio of SSZ: total weight of LTSP, while the percent drug loading and encapsulation efficiency of SSZ was 4.7 and 62.85 ± 0.3 in the TSP nanoformulation. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that both formulations formed spherical micelles and vesicles with globule sizes of 25 ± 1.2 nm and 100 ± 20.5 nm respectively. The cell toxicity evaluations showed that both LTSP and TSP nanoformulations without drug were nontoxic (at the range of this experiment) for Human Dermal Fibroblasts (HDF) as a normal cell line but SSZ loaded nanoformulation exhibited increased cell toxicity with half-maximal inhibitory concentration (IC50) of 940 µM for SSZ alone to near 240 µM for SSZ loaded nanoformulation (approximately four times). In vitro release experiments exhibited sustained release of SSZ from both nanoformulations. The LTSP micellar/liposomal and TSP micellar/niosomal nanoformulation for SSZ delivery can be considered as appropriate approaches for improving its bioavailability and probably they are good candidates for future clinical investigations. © 2022 Faculty of Engineering, Alexandria Universit

Formulation of Isopropyl Isothiocyanate Loaded Nano Vesicles Delivery Systems: In Vitro Characterization and In Vivo Assessment

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles