In this work, design, synthesis, and screening of thiophene carboxamides 4–13 and 16–23 as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic inhibitors was reported. All compounds were screened against two gastrointestinal solid cancer cells, HepG-2 and HCT-116 cell lines. The most active cytotoxic derivatives 5 and 21 displayed 2.3- and 1.7-fold higher cytotoxicity than Sorafenib against HepG-2 cells. Cell cycle and apoptosis analyses for compounds 5 and 21 showed cells accumulation in the sub-G1 phase, and cell cycle arrest at G2/M phase. The apoptotic inducing activities of compounds 5 and 21were correlated to the elevation of p53, increase in Bax/Bcl-2 ratio, and increase in caspase-3/7.Compounds 5 and 21 showed potent inhibition againstVEGFR-2 (IC50 = 0.59 and 1.29 μM) and β-tubulin polymerization (73% and 86% inhibition at their IC50 values).Molecular docking was performed with VEGFR-2 and tubulin binding sites to explain the displayed inhibitory activities.

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A new series of pyridine and pyrimidine derivatives is designed and synthesized as potential antitumor molecules. The tested compounds show promising in vitro cytotoxic activity against HL-60 cell line as eight compounds: 4, 6, 11, 13, 14, 15, 18 and 21 exhibit potent cytotoxic activity in sub-micromolar concentration higher than the combretastatin A4 (CA-4). Compound 21 shows a cytotoxic activity 5-fold more potent than CA-4 on HL-60 cells. DNA-Flow cytometry cell cycle analysis and annexin-V assay on HL-60 cells show that compounds 4, 18 and 21 exhibit potent cell growth inhibition, cell cycle arrest at G/M phase and pro-apoptotic inducing activities. The percentage inhibition assay of β-tubulin polymerization on HL-60 cells shows that the antitumor activity of the tested compounds appears to correlate well with its ability to inhibit β-tubulin polymerization. In addition, enzyme-linked immunosorbene assay (ELlSA) measurement for compound 21 shows apoptotic inducing activities through significant up regulation of p53, Bax/Bcl-2 ratio and caspase-3 proteins parallel to down regulation of the level of survivin proteins.

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Background: Benzo[a]anthracene (BAA), also known as "tetraphene" belongs to the polycyclic aromatic hydrocarbons (PAHs) which are considered as an important class of environmental genotoxins. The present work focused on the evaluation of the efficiency of the biodegradation of the BAA by Bacillus amyloliquefaciens using animal bioassays, which include micronucleus (MN) and DNA fragmentation as end point of genotoxicity of the resulting metabolites from BAA biodegradation. Results: B. amyloliquefaciens was exposed to different doses of γ radiation (0.5, 1.0, 1.5, and 2.0 kGy) kGy. The colonies for the wild strain and its variants obtained after radiation were counted. The final counts for variant 3 (V3), variant 4 (V4), and variant 5 (V5) have been increased from its initial count by (0.3, 0.48, and 0.1 log cycle) respectively at 1 mg/ 100 ml (BAA). For animal bioassay, male mice were divided into seven groups; control group received vehicle only, groups II and III were injected with 5 and 10 mg/kg b.wt (BAA) respectively, and groups IV, V, VI, and VII were injected with the residues of BAA after biodegradation with wild type, V3, V4, and V5 of B. amyloliquefaciens respectively. Conclusions: Results of the micronucleus test and the DNA fragmentation as end point of genotoxicity of (BAA) indicated that B. amyloliquefaciens have the efficiency in biodegradation of (BAA) to nongenotoxic metabolites where (V3) and (V4) are more efficient than the wild type and (V5). So B. amyloliquefaciens could solve the problem of soil and water contamination by oil spill or industrial petroleum waste by ecofriendly manner.

P UNICA granatum (Pg) is an edible fruit known as pomegranate, which is a rich source of polyphenolic compounds and has antioxidant activity. Many studies have been conducted on extracts of various parts of Pg which may have genotoxic effects. However, the purpose of the present study is to assess, for the first time, the radio-protective effect of Pg juice, the safest part of the fruit, against γ-irradiation-induced biochemical and cytogenetic damage in rats by modulating the lipid profile, and the esterases (acetylcholinesterase AchE, carboxylesterase CarE and paraoxonase PON) activity as biomarkers that provide information on the nervous system's integrity, metabolism, and anti-oxidative defenses respectively. Male rats were divided into six groups, group I is the control, group II received Pg juice (400 mg/kg/day) divided into two equal doses twice daily (with 12 h interval) for 30 days, group III and V received 4 Gy and 8 Gy of γ-radiation respectively, group IV and VI received Pg juice for 30 days before being irradiated with 4 and 8Gy of γ-radiation respectively. Radiation altered the levels of CarE and PON activity in plasma and liver, as well as plasma total cholesterol, triglycerides, high-density lipoprotein HDL, low-density lipoprotein LDL, and very low-density lipoprotein VLDL. In comparison to the control group, Pretreatment with Pg juice significantly improves these values and reduced DNA fragmentation significantly. It is possible to conclude that Pg juice protects against ionizing irradiation, which causes biochemical and cytogenetic damage, by modulating anti-oxidative defenses and metabolism.

Four different cytokines (IL1-β, IL-6, IL-10 and TNF-α) and the cytokinesis-block micronucleus (CBMN) cytome assay investigations were evaluated in six human blood samples. They were divided into the control (nonirradiated) and five gamma-irradiated groups which were exposed to five different doses (0.5, 1, 2, 4 and 8 Gy). Blood groups were cultured in triplets for 72 h following 1 h of irradiation. Immunological and cytogenetics were investigated parallelly at different irradiation doses to understand the connection between them. Our aim is anchoring the active proliferation action of cytokines by presence of binucleated cells and resting immune system by mononuclear cell. Also, cell death by increasing necrotic cell count and TNF-α concentration. When compared with the control group, 0.5, 1, 2 and 4 Gy irradiation groups recorded a gradual increase in the cytokines levels, an increase in the total micronucleated cells (binucleated and mononucleated cells), an increase in necrotic and apoptotic cells counts. While 8 Gy irradiation leads to depletion in TNF-α concentration, although the number of necrotic cells was high.