Synthesis,antitumor activity and molecular docking study of some novel 3-benzyl-4(3H)quinazolinone analogues

A novel series of 3-benzyl-substituted-4(3H)-quinazolinones were designed, synthesized and evaluated for their in vitro antitumor activity. The results of this study demonstrated that 2-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide, 2-(3-benzyl-6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide and 3-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)-propanamide have shown amazing broad spectrum antitumor activity with mean GI₅₀ (10.47, 7.24 and 14.12?µM. respectively), and are nearly 1.5–3.0-fold more potent compared with the positive control 5-FU with mean GI₅₀, 22.60?µM. On the other hand, compounds 6 and 10 yielded selective activities toward CNS, renal and breast cancer cell lines, whereas compound 9 showed selective activities towards leukemia cell lines. Molecular docking methodology was performed for compounds 7 and 8 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib, while compound 11 into ATP binding site of B-RAF kinase inhibited the growth of melanoma cell lines through inhibition of B-RAF kinase, similar to PLX4032.     

Cunninghamella echinulata a new biosorbent of metal ions from polluted water in Egypt

Thirty-two fungal species were isolated from a polluted watercourse near the Talkha fertilizer plant, Mansoura Province, Egypt. Aspergillus niger, A. flavus, Cunninghamella echinulata and Trichoderma koningii were isolated frequently. On the basis of its frequency, Cunninghamella echinulata was chosen for biosorption studies. Free and immobilized biomass of C. echinulata sequestered ions in this decreasing sequence is: Pb >Cu >Zn. The effects of biomass concentration, pH and time of contact were investigated. The level of ion uptake rose with increasing biomass. The maximum uptake for lead (45 mg/g), copper (20 mg/g) and zinc (18.8 mg/g) occurred at 200 mg/L biomass. The uptake rose with increasing pH up to 4 in the case of Pb and 5 in the case of Cu and Zn. Maximum uptake for all metals was achieved after 15 min. Ion uptake followed the Langmuir adsorption model, permitting the calculation of maximum uptake and affinity coefficients. Treatment of C. echinulata biomass with NaOH improved biosorbent capacity, as did immobilization with alginate. Immobilized biomass could be regenerated readily by treatment with dilute HCl. The biomass-alginate complex efficiently removed Pb, Zn and Cu from polluted water samples. Therefore,Cunninghamella echinulata could be employed either in free or immobilized form as a biosorbent of metal ions in waste water.     

Melatonin Protects Against Diazinon-Induced Neurobehavioral Changes in Rats

Diazinon is an organophosphorous pesticide with a prominent toxicity on many body organs. Multiple mechanisms contribute to diazinon-induced deleterious effects. Inhibition of acetyl-cholinesterase, cholinergic hyperstimulation, and formation of reactive oxygen species may play a role. On the other hand, melatonin is a pineal hormone with a well-known potent antioxidant activity and a remarkable modulatory effect on many behavioral processes. The present study revealed that oral diazinon administration (25 mg/kg) increased anxiety behavior in rats subjected to elevated plus maze and open-field tests possibly via the induction of changes in brain monoamines levels (dopamine, norepinephrine, and serotonin). Additionally, brain lipid peroxides measured as malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) levels were elevated, while the activity of brain glutathione peroxidase enzyme was reduced by diazinon. Co-administration of oral melatonin (10 mg/kg) significantly attenuated the anxiogenic activity of diazinon, rebalanced brain monoamines levels, decreased brain MDA and TNF-α levels, and increased the activity of brain glutathione peroxidase enzyme.