Date fruit melanin is primarily based on (-)-epicatechin proanthocyanidin oligomers.

Plant-based melanin seems to be abundant, but it did not receive scientific attention despite its importance in plant biology and medicinal applications, e.g. photoprotection, radical scavenging, antimicrobial properties, etc. Date fruit melanin (DM) has complex, graphene-like, polymeric structure that needs characterization to understand its molecular properties and potential applications. This study provides the first investigation of the possible molecular composition of DM. High performance size-exclusion chromatography (HPSEC) suggested that DM contains oligomeric structures (569-3236 Da) and transmission electron microscopy (TEM) showed agglomeration of these structures in granules of low total porosity (10-1000 Å). Nuclear magnetic resonance (NMR) spectroscopy provided evidence for the presence of oligomeric proanthocyanidins and electron paramagnetic resonance (EPR) spectroscopy revealed a g-factor in the range 2.0034-2.005. Density functional theory (DFT) calculations suggested that the EPR signals can be associated with oligomeric proanthocyanidin structures having 4 and above molecular units of (-)-epicatechin. The discovery of edible melanin in date fruits and its characterization are expected to open a new area of research on its significance to nutritional and sensory characteristics of plant-based foods.

In Silico Design, Synthesis, and Evaluation of Novel Enantiopure Isoxazolidines as Promising Dual Inhibitors of α-Amylase and α-Glucosidase.

Isoxazolidine derivatives were designed, synthesized, and characterized using different spectroscopic techniques and elemental analysis and then evaluated for their ability to inhibit both α-amylase and α-glucosidase enzymes to treat diabetes. All synthesized derivatives demonstrated a varying range of activity, with IC50 values ranging from 53.03 ± 0.106 to 232.8 ± 0.517 µM (α-amylase) and from 94.33 ± 0.282 to 258.7 ± 0.521 µM (α-glucosidase), revealing their high potency compared to the reference drug, acarbose (IC50 = 296.6 ± 0.825 µM and 780.4 ± 0.346 µM), respectively. Specifically, in vitro results revealed that compound 5d achieved the most inhibitory activity with IC50 values of 5.59-fold and 8.27-fold, respectively, toward both enzymes, followed by 5b. Kinetic studies revealed that compound 5d inhibits both enzymes in a competitive mode. Based on the structure-activity relationship (SAR) study, it was concluded that various substitution patterns of the substituent(s) influenced the inhibitory activities of both enzymes. The server pkCSM was used to predict the pharmacokinetics and drug-likeness properties for 5d, which afforded good oral bioavailability. Additionally, compound 5d was subjected to molecular docking to gain insights into its binding mode interactions with the target enzymes. Moreover, via molecular dynamics (MD) simulation analysis, it maintained stability throughout 100 ns. This suggests that 5d possesses the potential to simultaneously target both enzymes effectively, making it advantageous for the development of antidiabetic medications.

In Vitro and In Silico Evaluation of Antiproliferative Activity of New Isoxazolidine Derivatives Targeting EGFR: Design, Synthesis, Cell Cycle Analysis, and Apoptotic Inducers.

A series of novel enantiopure isoxazolidine derivatives were synthesized and evaluated for their anticancer activities against three human cancer cell lines such as human breast carcinoma (MCF-7), human lung adenocarcinoma (A-549), and human ovarian carcinoma (SKOV3) by employing MTT assay. The synthesized compounds were characterized by NMR and elemental analysis. Results revealed that all the synthesized compounds displayed significant inhibition towards the tested cell lines. Among them, 2g and 2f, which differ only by the presence of an ester group at the C-3 position and small EDG (methyl) at the C-5 position of the phenyl ring (2g), were the most active derivatives in attenuating the growth of the three cells in a dose-dependent manner. The IC50 for 2g were 17.7 ± 1 µM (MCF-7), 12.1 ± 1.1 µM (A-549), and 13.9 ± 0.7 µM (SKOV3), and for 2f were 9.7 ± 1.3µM (MCF-7), 9.7 ± 0.7µM (A-549), and 6.5 ± 0.9µM (SKOV3), respectively, which were comparable to the standard drug, doxorubicin. The enzymatic inhibition of 2f and 2g against EGFR afforded good inhibitory activity with IC50 of 0.298 ± 0.007 µM and 0.484 ± 0.01 µM, respectively, close to the positive control, Afatinib. Compound 2f arrested the cell cycle in the S phase in MCF-7 and SKOV3 cells, and in the G2/M phase in the A549 cell; however, 2g induced G0/G1 phase cell cycle arrest, and inhibited the progression of the three cancer cells, together with significant apoptotic effects. The docking study of compounds 2f and 2g into EGFR ATP-active site revealed that it fits nicely with good binding affinity. The pharmacokinetic and drug-likeness scores revealed notable lead-like properties. At 100 ns, the dynamic simulation investigation revealed high conformational stability in the EGFR binding cavity.

A New, Extremely Sensitive, Turn-Off Optical Sensor Utilizing Schiff Base for Fast Detection of Cu(II).

Throughout this research, a unique optical sensor for detecting one of the most dangerous heavy metal ions, Cu(II), was designed and developed. The (4-mercaptophenyl) iminomethylphenyl naphthalenyl carbamate (MNC) sensor probe was effectively prepared. The Schiff base of the sensor shows a "turn-off" state with excellent sensitivity to Cu(II) ions. This innovative fluorescent chemosensor possesses distinctive optical features with a substantial Stocks shift (about 114 nm). In addition, MNC has remarkable selectivity for Cu(II) relative to other cations. Density functional theory (DFT) and the time-dependent DFT (TDDFT) theoretical calculations were performed to examine Cu(II) chelation structures and associated electronic properties in solution, and the results indicate that the luminescence quenching in this complex is due to ICT. Chelation-quenched fluorescence is responsible for the internal charge transfer (ICT)-based selectivity of the MNC sensing molecule for Cu(II) ions. In a 1:9 (v/v) DMSO-HEPES buffer (20 mM, pH = 7.4) solution, Fluorescence and UV-Vis absorption of the MNC probe and Cu(II) ions were investigated. By utilizing a solution containing several metal ions, the interference of other metal ions was studied. This MNC molecule has outstanding selectivity and sensitivity, as well as a low LOD (1.45 nM). Consequently, these distinctive properties enable it to find the copper metal ions across an actual narrow dynamic range (0-1.2 M Cu(II)). The reversibility of the sensor was obtained by employing an EDTA as a powerful chelating agent.

Synthesis, characterization, anticancer activity and molecular docking of metal complexes bearing a new Schiff base ligand.

2-((E)-((4-(((E)-4-Nitrobenzylidene)amino)phenyl)imino)methyl)naphthalen-1-ol, was synthesised followed by metalation with Fe(III), Co(III), Cu(II), Zn(II) and Ni(II) metals. The compounds were characterised by different methods CHN, AAS, IR, NMR, XRD, TGA and UV-Vis. The results reveal that the ligand has bidentate behavior, and it is bound with metals by a coordination bond through both the nitrogen atom of the azomethine group and the oxygen atom, this provided an octahedral geometry. The X-ray diffraction of the compounds indicate that the ligands and complexes of Co(III), Fe(III) and Zn(II) have a crystalline nature, whereas the Ni(II) and Cu(II) have an amorphous structure. The agar diffusion method (hole plate) was used to evaluate the ligand's and its complexes' antibacterial and antifungal effects on Salmonella enterica serovar typhi and Candida albicans, respectively. It was observed that the Fe(III) complex had the best activity among the compounds against microbial strains. Cytotoxicity of new metal complexes was also assessed against A549, HepG-2 and PC-3 cancer cells. Results demonstrated that the Cu(II) complex displayed the preeminent activity among the synthesised compounds against all the tested cell lines. Furthermore, molecular docking simulation revealed that the Fe(III) complex is shown to have a high affinity with the active sites of two targets of microbial strains. Also, the Cu(II) complex shown to has a high affinity with the active sites of three targets of A-549, HepG-2 and PC-3 cancer cells, which was confirmed by the formation of the different modes of interaction.Communicated by Ramaswamy H. Sarma.

Synthesis, Molecular Docking, and Bioactivity Study of Novel Hybrid Benzimidazole Urea Derivatives: A Promising α-Amylase and α-Glucosidase Inhibitor Candidate with Antioxidant Activity.

A novel series of benzimidazole ureas 3a-h were elaborated using 2-(1H-benzoimidazol-2-yl) aniline 1 and the appropriate isocyanates 2a-h. The antioxidant and possible antidiabetic activities of the target benzimidazole-ureas 3a-h were evaluated. Almost all compounds 3a-h displayed strong to moderate antioxidant activities. When tested using the three antioxidant techniques, TAC, FRAP, and MCA, compounds 3b and 3c exhibited marked activity. The most active antioxidant compound in this family was compound 3g, which had excellent activity using four different methods: TAC, FRAP, DPPH-SA, and MCA. In vitro antidiabetic assays against α-amylase and α-glucosidase enzymes revealed that the majority of the compounds tested had good to moderate activity. The most favorable results were obtained with compounds 3c, 3e, and 3g, and analysis revealed that compounds 3c (IC50 = 18.65 ± 0.23 µM), 3e (IC50 = 20.7 ± 0.06 µM), and 3g (IC50 = 22.33 ± 0.12 µM) had good α-amylase inhibitory potential comparable to standard acarbose (IC50 = 14.21 ± 0.06 µM). Furthermore, the inhibitory effect of 3c (IC50 = 17.47 ± 0.03 µM), 3e (IC50 = 21.97 ± 0.19 µM), and 3g (IC50 = 23.01 ± 0.12 µM) on α-glucosidase was also comparable to acarbose (IC50 = 15.41 ± 0.32 µM). According to in silico molecular docking studies, compounds 3a-h had considerable affinity for the active sites of human lysosomal acid α-glucosidase (HLAG) and pancreatic α-amylase (HPA), indicating that the majority of the examined compounds had potential anti-hyperglycemic action.