Background: Thiazole and thiosemicarbazone derivatives are known to have potential anticancer activity with a mechanism of action related to inhibition of matrix metalloproteinases, kinases and anti-apoptotic BCL2 family proteins. Materials and Methods: A novel three series of 5-(1-(2-(thiazol-2-yl)hydrazono)ethyl) thiazole derivatives were prepared in a one-pot three-component reaction using 2-(2-benzylidene hydrazinyl)-4-methylthiazole as a starting precursor. MS, IR, 1 H-NMR and 13 C-NMR were used to elucidate the structures of the synthesized compounds. Most of the synthesized products were evaluated for their in vitro anticancer screening against HCT-116, HT-29 and HepG2 using the MTT colorimetric assay. Results: The results indicated that compounds 4c, 4d and 8c showed growth inhibition activity against HCT-116 with IC 50 values of 3.80 ± 0.80, 3.65 ± 0.90 and 3.16 ± 0.90 μM, respectively, compared to harmine (IC 50 = 2.40 ± 0.12 μM) and cisplatin (IC 50 = 5.18 ± 0.94 μM) reference drugs. Also, compounds 8c, 4d and 4c showed promising IC 50 values of 3.47 ± 0.79, 4.13 ± 0.51 and 7.24 ± 0.62 μM, respectively, against the more resistant human colorectal cancer (HT-29) cell line compared with harmine (IC 50 = 4.59 ± 0.67 μM) and cisplatin (IC 50 = 11.68 ± 1.54 μM). On the other hand, compounds 4d, 4c, 8c and 11c were the most active (IC 50 values of 2.31± 0.43, 2.94 ± 0.62, 4.57 ± 0.85 and 9.86 ± 0.78 μM, respectively) against the hepatocellular carcinoma (HepG2) cell line compared with harmine (IC 50 = 2.54 ± 0.82 μM) and cisplatin (IC 50 = 41 ± 0.63 μM). The study also suggested that the mechanism of the anticancer action exerted by the most active compounds (4c, 4d and 8c) inside HCT-116 cells was apoptosis through the Bcl-2 family. Conclusion: Thiazole scaffolds 4c, 4d and 8c showed anticancer activities in the micromolar range and are appropriate as a candidate for cancer treatment.

This study aimed to elucidate whether quercetin treatment could modulate acrylamide (ACR)‐induced DNA damage and oxidative changes in rat brain, liver, kidneys and testes tissues. Fifty adult albino rats were divided into five groups. The first group served as normal control, second group received 50 mg/kg quercetin (QTN) and third group received 20 mg/kg ACR. Fourth and fifth groups received dose of ACR along with 25 or 50 mg/kg QTN, respectively. ACR and QTN were given by oral administrations for 30 days. The results showed that, ACR administration induced significant elevation of alanine transferase, aspartate transferase activities, urea, creatinine and Malondialdehyde levels in serum, whereas, Acetylcholine esterase and testosterone levels were reduced after ACR administration. Moreover, ACR treatment increased Glutathione‐S‐transferase, Myeloperoxidase, Glutathione peroxidase activity, 8‐hydroxy deoxyguanosine, tumor necrosis factor‐α and nitric oxide contents in all tissues. QTN significantly improved the previous parameters. It played a role in ameliorating toxic effects of ACR in rats by reducing oxidative stress. Practical Applications Acrylamide was found in various fried, deep fried and oven‐baked foods that are regularly consumed like chips, crisps and bread, also biscuits, crackers and breakfast cereals. Acrylamide exposure led to increase of alanine transferase, aspartate transferase activities, urea, creatinine and Malondialdehyde levels in serum, whereas, Acetylcholine esterase and testosterone levels were reduced. Moreover, ACR treatment increased Glutathione‐S‐transferase, Myeloperoxidase, Glutathione peroxidase activity, 8‐hydroxy deoxyguanosine, tumor necrosis factor‐α and nitric oxide contents in all tissues. Our study revealed the protective role of quercetin on acrylamide‐induced oxidative stress in rats. Quercetin regulate the generation of inflammatory markers and increasing antioxidant enzyme activity in rat liver, kidneys, brain and testes tissues.

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Carvedilol (CRV) is a non-selective third generation beta-blocker used to treat hypertension, congestive heart failure and angina pectoris. Oral administration of CRV showed poor bioavailability (25%), which might be ascribed to its extensive first-pass metabolism. Buccal delivery is known to boost drugs bioavailability. The aim of this study is to investigate the efficacy of bilosomes-based mucoadhesive carvedilol nanosponge for enhancing the oral bioavailability of CRV. The bilosomes were prepared, optimized and characterized for particle size, surface morphology, encapsulation efficiency and ex-vivo permeation studies. Then, the optimized formula was incorporated into a carboxymethyl cellulose/hydroxypropyl cellulose (CMC/HPC) composite mixture to obtain buccal nanosponge enriched with CRV bilosomes. The optimized bilosome formula (BLS9), showing minimum vesicle size, maximum entrapment, and highest cumulative in vitro release, exhibited a spherical shape with 217.2 nm in diameter, 87.13% entrapment efficiency, and sustained drug release for up to 24 h. In addition, ex-vivo drug permeation across sheep buccal mucosa revealed enhanced drug permeation with bilosomal formulations, compared to aqueous drug suspension. Consecutively, BLS9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain bilosomal nanosponge to enhance CRV buccal delivery. Morphological analysis of the prepared nanosponge revealed improved swelling with a porosity of 67.58%. The in vivo assessment of rats indicated that CRV-loaded nanosponge efficiently enhanced systolic/diastolic blood pressure, decreased elevated oxidative stress, improved lipid profile and exhibited a potent cardio-protective effect. Collectively, bilosomal nanosponge might represent a plausible nanovehicle for buccal delivery of CRV for effective management of hypertension.

Imidacloprid may induce oxidative stress leading to generate free radicals and alternate oxygen free radical scavenging enzyme system. This study aims to investigate the hepatoprotective effect of broccoli water extract and ferulic acid on imidacloprid induced oxidative stress and DNA damage in male albino rats. Rats were co-treated with broccoli water extract (200 mg/kg) or ferulic acid (20 mg/kg) with imidacloprid (80 mg/kg) orally for 28 days.The results revealed that imidacloprid induced high serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). However, administration of broccoli and ferulic acid reduced these parameters. Broccoli and ferulic acid significantly (P<0.05) attenuated the imidacloprid-induced increases in lipid peroxidation (LPO), tumor necroses factor α (TNF-α) and nitric oxide (NO) contents and meyloperoxidase (MPO), glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD) activities. Imidacloprid decreased reduced glutathione (GSH) while co-treatment with broccoli and ferulic acid significantly (P<0.05) improved the level of GSH. DNA damage as assessed by comet assay was increased in imidacloprid-treated group. However, DNA damage was decreased in M ahgoub M . A hm ed1 and Saw san A . N asr ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ ‫ــــــــــــــــــــــــــــــــــ‬ ‫ـــــــــــــــــــــــ‬ ‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ 2 broccoli and ferulic acid treated groups. The possible mechanism of broccoli and ferulic acid extract on imidacloprid might be due to decreasing oxidative stress (LPO, NO and DNA damage) and increasing GSH content. Thus, broccoli and ferulic acid was suggested to protected rat's liver against imidacloprid-induced oxidative stress and DNA damage in liver. : Unifying mechanism for eye toxicity, Electron transfer, reactive oxygen species, antioxidant benefits, cell Signaling and cell Membranes. Cell Membrane Free Radical Research 2: 56-69. Lowry O.H., Roseborough N.J., Farr A.L., and Randall R.L. (1951): Protein measurement with phenol reagent. Journal of Biological Chemistry. 193 (1): 265-275. Marks P.A. (1961): Enzymes of the pentose phosphate pathway. Methods Med. Res. 9: 24-35. Moreno D.A., Carvaja M., López-Berenguer C. and García-Viguera N. (2006): Chemical and biological characterisation of nutraceutical compounds of broccoli. J Pharm Biomed Anal. 41: 1508-1522. Olsen R.L. and Little C. (1983): Purification and some properties of myeloperoxidase and eosinophil peroxidase from human blood. Biochem. J. 209 (3): 781-787. Ou S. and Kwok K. C. (2004): Ferulic acid: pharmaceutical functions, preparation and applications in foods. J Sci. Food and Agric. 84 (11): 1261-1269. Podsedek A. (2007): Natural antioxidants and antioxidant capacity of Brassica vegetables: a review. LWT 40: 1-11. Rukkumani R., Aruna K., Suresh Varma P., Padmanabhan L. and Me...