Design, Synthesis, and Spectroscopic Studies of Some New α-Aminophosphonate Analogues Derived from 4-Hydroxybenzaldehyde with Special Reference to Anticancer Activity.

Introduction: As biological activity components, α-aminophosphonates and their moieties play important roles in medicinal chemistry. Alpha-phosphonic acids are significant α-amino acid counterparts. Due to its strong biological activity, this class of molecule has recently been discovered to have numerous medical applications. Results and Discussion: A new class of α-aminophosphonates and arylidene derivatives was synthesized. Various spectroscopic and elemental analyses were used to confirm the prepared products. The produced materials were tested as anticancer against breast carcinoma cells and normal human cells (PBMC). Besides the analysis results, it was found that (7b, 4c, 5k, 6, 5a, 7c, 5f, 5b, and 5g) against MCF-7 line cells. As a reference anticancer drug, 5-fluorouracil was used. The anticancer activities showed that the compounds 7b, 4c, containing α-aminophosphonate and Schiff base groups, respectively, showed high inhibition activity against the MCF-7 cell line, with 94.32% and 92.45% inhibition compared to the inhibition by 5-FU with 96.02% inhibition. The results showed that the compounds 5k, 7b, 6, and 5a, respectively, had very low activity against normal human cells PBMC, with 12.77%, 13%, 13.13%, and 17.88% inhibition compared to the inhibition by 5-FU with 12.50% inhibition. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor, thymidylate synthase, was determined using molecular docking (pdb code: 1AN5). Conclusion: α-aminophosphonate derivatives, arylidines, and disphosphonate derivatives derived from 4-hydroxybenzaldehyde were synthesized, purified, elucidated by spectroscopic analysis, and finally tested against carcinoma breast cancer to give high to moderate to low activity.

Grafting of Thiazole Derivative on Chitosan Magnetite Nanoparticles for Cadmium Removal-Application for Groundwater Treatment.

The synthesis and developments of magnetic chitosan nanoparticles for high efficiency removal of the cadmium ions from aquatic medium are one of the most challenging techniques. Highly adsorptive composite (MCH-ATA) was produced by the reaction of chitosan with formaldehyde and amino thiazole derivative. The sorbent was characterized by FTIR, elemental analyses (EA), SEM-EDX, TEM analysis, TGA and titration (volumetric). The modified material includes high nitrogen and sulfur contents (i.e., 4.64 and 1.35 mmol g-1, respectively), compared to the pristine material (3.5 and 0 mmol g-1, respectively). The sorption was investigated for the removal of Cd(II) ions from synthetic (prepared) solution before being tested towards naturally contaminated groundwater in an industrial area. The functionalized sorbent shows a high loading capacity (1.78 mmol Cd g-1; 200 mg Cd g-1) compared to the pristine material (0.61 mmol Cd g-1; 68.57 mg Cd g-1), while removal of about 98% of Cd with capacity (6.4 mg Cd g-1) from polymetallic contaminated groundwater. The sorbent displays fast sorption kinetics compared to the non-modified composite (MCH); 30 min is sufficient for complete sorption for MCH-ATA, while 60-90 min for the MCH. PFORE fits sorption kinetics for both sorbents, whereas the Langmuir equation fits for MCH and Langmuir and Sips for MCH-ATA for sorption isotherms. The TEM analysis confirms the nano scale size, which limits the diffusion to intraparticle sorption properties. The 0.2 M HCl solution is a successful desorbing agent for the metal ions. The sorbent was applied for the removal of cadmium ions from the contaminated underground water and appears to be a promising process for metal decontamination and water treatment.

Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect.

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.

Thiazolidinedione Derivatives: In Silico, In Vitro, In Vivo, Antioxidant and Anti-Diabetic Evaluation.

This work aimed to synthesize a new antihyperglycemic thiazolidinedione based on the spectral data. The DFT\B3LYP\6-311G** level of theory was used to investigate the frontier molecular orbitals (FMOs), chemical reactivity and map the molecular electrostatic potentials (MEPs) to explain how the synthesized compounds interacted with the receptor. The molecular docking simulations into the active sites of PPAR-γ and α-amylase were performed. The in vitro potency of these compounds via α-amylase and radical scavenging were evaluated. The data revealed that compounds (4-6) have higher potency than the reference drugs. The anti-diabetic and anti-hyperlipidemic activities for thiazolidine-2,4-dione have been investigated in vivo using the alloxan-induced diabetic rat model along with the 30 days of treatment protocol. The investigated compounds didn't show obvious reduction of blood glucose during pre-treatments compared to diabetic control, while after 30 days of treatments, the blood glucose level was lower than that of the diabetic control. Compounds (4-7) were able to regulate hyperlipidemia levels (cholesterol, triglyceride, high-density lipoproteins and low- and very-low-density lipoproteins) to nearly normal value at the 30th day.

Antibacterial and molecular docking studies of newly synthesized nucleosides and Schiff bases derived from sulfadimidines.

A new series of nucleosides, moieties, and Schiff bases were synthesized from sulfadimidine. Infrared (IR), 1HNMR, 13C NMR, and mass spectrometry techniques and elemental analysis were employed to elucidate the synthesized compounds. The prepared analogues were purified by different chromatographic techniques (preparative TLC and column chromatography). Molecular docking studies of synthesized compounds 3a, 4b, 6a, and 6e demonstrated the binding mode involved in the active site of DNA gyrase. Finally, all synthesized compounds were tested against selected bacterial strains. The most effective synthesized compounds against S. aureus were 3a, 4d, 4b, 3b, 3c, 4c, and 6f, which exhibited inhibition zones of inhibition of 24.33 ± 1.528, 24.67 ± 0.577, 23.67 ± 0.577, 22.33 ± 1.528, 18.67 ± 1.528 and 19.33 ± 0.577, respectively. Notably, the smallest zones were observed for 4a, 6d, 6e and 6g (6.33 ± 1.528, 11.33 ± 1.528, 11.67 ± 1.528 and 14.66 ± 1.155, respectively). Finally, 6b and 6c gave negative zone values. K. pneumoniae was treated with the same compounds and the following results were obtained. The most effective compounds were 4d, 4c, 4b and 3c, which showed inhibition zones of 29.67 ± 1.528, 24.67 ± 0.577, 23.67 ± 1.155 and 19.33 ± 1.528, respectively, followed by 4a and 3d (15.33 ± 1.528 for both), while moderate results (13.67 ± 1.155 and 11.33 ± 1.528) were obtained for 6f and 6g, respectively. Finally, 6a, 6b, 6c, 3a, and 3b did not show any inhibition. The most effective compounds observed for the treatment of E. coli were 4d, 4b, 4c, 3d, 6e and 6f (inhibition zones of 26.33 ± 0.577, 21.67 ± 1.528, 21.67 ± 1.528, 19.67 ± 1.528, 17.67 ± 1.155 and 16.67 ± 1.155, respectively). Compounds 3b, 3c, 6a, 6c, and 6g gave moderate results (13.67 ± 1.528, 12.67 ± 1.528, 11.33 ± 0.577, 15.33 ± 1.528 and 12.67 ± 1.528, respectively), while 6b showed no effect. The MIC values against S. aureus ranged from 50 to 3.125 mg, while those against E. coli and K. pneumoniae ranged from 50 to 1562 mg. In vitro, the antibacterial effects were promising. Further research is required to study the in vivo antibacterial effects of these compounds and determine therapeutic doses.

Synthesis, spectroscopic and molecular docking studies on new schiff bases, nucleosides and α-aminophosphonate derivatives as antibacterial agents.

New Nucleosides, analogues derived from 1, 3, 4-oxadiazole, arylidene analogues and α-aminophosphonate were prepared. Infrared (IR), elemental analysis and 1HNMR elucidated nucleosides; arylidines and phosphonate derivatives. The prepared derivatives were purified and allowed to test against bacteria strains. Phosphonate derivative 12a showed the higher antibacterial against E. coli with inhibition zone 35 mm, P. aeruginosa with inhibition zone 30 and S. aureus with inhibition zone 22 while compounds 4, 6d, 9a, 9c and 12c showed moderate to weak activity against these bacteria species with inhibition zones ranged from 12 mm to 24 mm. The molecular docking studies was applied on compound 12a, which showed the binding at the active DNA Gyrase.

Susceptibility Assessment of Multidrug Resistant Bacteria to Natural Products.

OBJECTIVE: The aim of this study was to examine the effect of some natural compounds against multidrug-resistant bacteria. METHODS: Forty-three bacterial strains were collected. Disc diffusion and minimum inhibitory concentration (MIC) tests were carried out for natural compounds including quercetin, Acacia nilotica, Syzygium aromaticum, and Holothuria atra. Scanning electron microscope analysis and bacterial DNA apoptosis assays were performed. RESULTS: Staphylococcus aureus strains were resistant to imipenim, ampicillin, and penicillin. Most Escherichia coli strains were resistant to amoxicillin, clavulanat, and ampicillin. Finally, tigecycline was effective with Klebsiella pneumoniae and was resistant to all antibiotics. Only S aromaticum had an antibacterial effect on K pneumoniae. Most S aureus strains were sensitive to S aromaticum, A nilotica, and quercetin. All examined natural extracts had no effect on E coli. Holothuria atra had no effect on any of the strains tested. Minimum inhibitory concentration and minimum bactericidal concentration values for examined plants against S aureus were 6.25 to 12, 1.6 to 3.2, and 9.12 to 18.24 mg/mL, respectively. Syzygium aromaticum was active against K pneumoniae with an MIC of 12.5 mg/mL. Scanning electron microscope analysis performed after 24 and 48 hours of incubation showed bacterial strains with distorted shapes and severe cell wall damage. Syzygium aromaticum, quercetin, and A nilotica showed clear fragmentations of S aureus DNA. CONCLUSIONS: Current findings confirmed the beneficial effect of using natural products such as clove (S aromaticum), quercetin, and A nilotica as a promising therapy to overcome multidrug resistant bacteria.