Design, synthesis, molecular docking, in silico ADMET profile and anticancer evaluations of sulfonamide endowed with hydrazone-coupled derivatives as VEGFR-2 inhibitors.

A new series of sulfonamide endowed with hydrazone coupled to dimethyl and/or diethyl malonates were prepared. Various sulfa drugs were diazotized and followed by coupling with active methylene of dimethyl and/or diethyl malonate to afford the new intermediates hydrazones 3a-c and 4a-c. The reactivity of hydrazone derivatives towards hydrazines was investigated. Thus, a novel series of 3,5-dioxopyrazolidine7a-cwere obtained by treatment with hydrazine hydrate. When hydrazones were allowed to react with phenyl hydrazine, the alkyl 2-((4-(N-(substituted)sulfamoyl)phenyl)diazenyl)-3-oxo-3-(2-phenylhydrazinyl)propanoateswere obtained 8a-c and/or 10a-c. Their anticancer activities were evaluated against HepG2, HCT-116 and MCF-7. HepG2 was the most sensitive one. In particular, compounds 7c, 7b and 10c were found to be the most potent derivatives with IC50 = 6.43 ± 0.5, 9.66 ± 0.8, 10.57 ± 0.9 µM, 8.65 ± 0.7, 7.49 ± 0.6, 14.29 ± 1.3 µM and 8.97 ± 0.7, 10.13 ± 0.9, 13.82 ± 1.1 µM respectively. Sorafenib and doxorubicin were used as reference drugs. The most potent derivatives 7a, 7b, 7c, 8c and 10c were tested for their cytotoxicity against normal VERO cell lines. Compounds 7a, 7b, 7c, 8c and 10c are respectively, 2.41, 4.85, 4.08, 3.23 and 5.89 fold times more toxic in HCT116 than in VERO normal cells. Moreover, the most active anti-proliferative derivatives 7a, 7b, 7c, 8c and 10c were subjected to further biological study to evaluate their inhibitory potentials against VEGFR-2. The tested compounds displayed high to good inhibitory activity with IC50 values ranging from 0.14 ± 0.02 to 0.23 ± 0.03 µM. Among them, compounds 7c, 7b and 10c were found to be the most potent derivative that inhibited VEGFR-2 at IC50 values of 0.14 ± 0.02, 0.15 ± 0.02 and 0.15 ± 0.02 µM respectively. sorafenib was used as reference drug. Furthermore, ADMET profile was evaluated for the four most active compounds in comparison to doxorubicin as a reference drug. The data obtained from docking studies were highly correlated with that obtained from the biological screening.

CHITOSAN NANOPARTICLES PREPARED FROM LUCILIA CUPRINA MAGGOTS AS ANTIBACTERIAL AGENT.

Chitosan were prepared from cuticle of Lucilia cuprina maggots with two steps; deproteinization and deacetylation. It was characterized with solubility and Fourier Transform Infrared spectroscopy (FT-IR). Chitosan was ball-milled to obtain the chitosan nanoparticles which characterized with dynamic light scattering (DLS) and transmission electron microscope (TEM). Chitosan nanoparticles with degree of deacetylation (DDA) 80.5% were showed antibacterial activities against Klebsiella pneumoniae and Bacillus subtilis. The mode of action of chitosan nanoparticles on the tested bacteria was studied by TEM. Leakage of some cell contents, cell deformation and rupture of cell were observed, therefore, the chitosan nanoparticles were observed to be a powerful antibacterial agent.

ANTIMICROBIAL ACTIVITIES OF CHITOSAN NANOPARTICLES PREPARED-FROM LUCILA CUPRINA MAGGOTS (DIPTERA: CALLIPHORIDAE).

Chitosan nanoparticles Were studied as antimicrobial agent. The antibacterial activity of chitosan nanoparticles were investigated against three Gram-negative bacteria; Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi, and three Gram-positive bacteria; Staphylococcus aureus, Enterococcus faecalis and Streptococcus pyogenes. The 'antifungal activity were examined against three fungi; Geotrichum candidum, Candida krusei and Candida parapsilosis. The antiviral activities were tested against three viruses; Rift Valley Fever (RVFV), Herpes simplex-I (HSV-1) and Coxsackie viruses. Chitosan nanoparticles were inhibited all bacteria and fungi except E. faecalis seemed to be resistant strain. Infectivity titers of all viruses were reduced by chitosan nanoparticles, which are a natural antimicrobial agent.