Design, synthesis, and molecular docking of new phenothiazine incorporated N-Mannich bases as promising antimicrobial agents.

The present work aims to synthesize four series of phenothiazine incorporation Mannich bases. Therefore, 10-methyl-10H-phenothiazine-3-sulfonamide (4) which was subjected to react with some secondary amines and formaldehyde to give the Mannich bases 5a-f, and 6-13. Compound 13 was then subjected to react with some secondary amines and formaldehyde to give the corresponding Mannich bases 14a-f. In total, twenty-two new compounds were synthesized and evaluated for in vitro growth inhibition activity against P. aeruginosa, E. coli, and S. aureus. Among the tested compounds, compounds 3, 5a, 5c, 6, 12, 13, 14d, and 14e exhibited good activity with a MIC value (12.5 µg/mL), compounds 5b, 10, 11, 14a, and 14c exhibited strong activity against the growth of S. aureus with a MIC value (6.25 µg/mL), and compound 14b superior against S. aureus with a MIC value (3.125 µg/mL) compared to drug reference ciprofloxacin with MIC value (2 µg/mL). The molecular docking investigation revealed the presence of many derivatives with high binding affinities and distinct interaction patterns with the target protein. Derivatives 14a-e emerged as the most promising possibilities, displaying the greatest binding energies and a varied variety of interaction types, including hydrogen bonding and pi interactions, over different distances, with derivative 14b exhibiting the highest binding energy at S = -8.3093 kcal/mol. These derivatives displayed superior binding affinities and various interaction mechanisms with the target protein, suggesting that they have great promise as lead compounds for future development into therapeutic medicines.

Preparation of Self-Healing Anthocyanidin-Containing Thermochromic Alginate Ink for Authentication Purposes.

Thermochromic inks have proven to be a promising security encoding approach for making commercially available products less susceptible to forgery. However, thermochromic inks have been plagued with poor durability. Thus, self-healable hydrogels can be used as self-repair inks with better durability. Herein, we combined hybrid cellulose nanofibers (CNFs) and sodium alginate (SA) with anthocyanidin(Cy)-based Brassica oleracea L. var. capitata extract in the existence of mordant (ferrous sulfate) to create a self-healing ink for authentication. CNFs were used as a reinforcement agent to enhance the mechanical strength of the sodium alginate hydrogel. Both durability and thermal stability were ensured using self-healing inks. Red cabbage was used to extract Cy-based chromophore as an environmentally friendly spectroscopic probe for immobilization into SA. Using varying concentrations of anthocyanidin, self-healable composite hydrogels (Cy@SA) with thermochromic properties were provided. Using the CIE Lab color coordinate system, homogeneous purple (569 nm) films were printed onto a sheet surface. Upon heating from 25 to 70 °C, the purple color changed to red (433 nm). Transmission electron microscopy was applied to study anthocyanidin/mordant (Cy/M) nanoparticles (NPs). The properties of the applied prints were analyzed using several methods. Both the hydrogel and stamped sheets were tested for their mechanical and rheological characteristics, respectively. Research on the nanocomposite ink (Cy@SA) antibacterial properties and cytotoxicity was also conducted.

Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors.

With the aim of developing cyclin-dependent kinase 2 (CDK2) inhibitors with strong antibreast cancer efficacy, new tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives were synthesized. The newly synthesized tri- and tetracyclic derivatives were achieved from the reaction of 4-(4-morpholin-4-yl-phenyl)-1,3,4,5,6,7-hexahydro-benzo[6,7]cyclohepta[1,2-d]pyrimidine-2-thione (5) with α-haloketone derivatives as hydrazonyl chlorides, phenacyl bromide derivatives, chloroacetone, and ethyl substituted acetate derivatives. The MCF-7 and MDA-MB-231 breast cancer cell lines were utilized to examine the anticancer properties. Compounds 5 and 8 were shown to be the most effective, with half-maximal inhibitory concentration (IC50 ) values between 5.73 and 9.11 µM, which are on the level with doxorubicin. Mechanistic studies showed that 5 and 8 caused tumor cell death by inducing apoptosis and they also produced cancer arrest in the S phase of the cell cycle. In addition, compounds 5 and 8 showed strong anti-CDK2 action (IC50 = 0.112 and 0.18 µM, respectively) comparable to roscovitine (IC50 = 0.127 µM). Moreover, the docking result demonstrated that derivatives 5 and 8 fit into the CDK2 active site in the proper orientation.

C-N Axial Chiral Hypervalent Iodine Reagents: Catalytic Stereoselective α-Oxytosylation of Ketones.

A simple synthesis of a library of novel C-N axially chiral iodoarenes is achieved in a three-step synthesis from commercially available aniline derivatives. C-N axial chiral iodine reagents are rarely investigated in the hypervalent iodine arena. The potential of the novel chiral iodoarenes as organocatalysts for stereoselective oxidative transformations is assessed using the well explored, but challenging stereoselective α-oxytosylation of ketones. All investigated reagents catalyse the stereoselective oxidation of propiophenone to the corresponding chiral α-oxytosylated products with good stereochemical control. Using the optimised reaction conditions a wide range of products was obtained in generally good to excellent yields and with good enantioselectivities.

Synthesis, characterisation, and reactivity of novel pseudocyclic hypervalent iodine reagents with heteroaryl carbonyl substituents.

Two new hypervalent iodine reagents containing furan and thiophene moieties in addition to a carbonyl group in the vicinity of the iodine atom were synthesised and characterised. The X-ray analysis of both compounds revealed a strong intramolecular contact between the carbonyl oxygen and the hypervalent iodine atom with tosylate as a counter ion. The two reagents showed a broad range of synthetic applications and proved to be versatile oxidizing agents.

Electron-Deficient Chiral Lactic Acid-Based Hypervalent Iodine Reagents.

Novel electron-deficient chiral hypervalent iodine reagents were prepared in good overall yields. The reactivity and stereoselectivity of these reagents in oxidative rearrangements of alkenes to α-aryl ketones were investigated. The results show that the new reagents have good reactivity and generate products with high enantiomeric excess.