Structure based design and anti-breast cancer evaluation of some novel 4-anilinoquinazoline derivatives as potential epidermal growth factor receptor inhibitors.

Quinazoline is one of the most widespread scaffolds amongst natural and synthetic bioactive compounds. Recently the quinazoline derivatives and in particular the 4-anilinoquinazolines have attracted much attention for their anticancer properties due to their capability to stabilize the kinase activity of epidermal growth factor receptor (EGFR). A series of fifteen previously designed and synthesized 4-anilinoquinazoline analogs (4-18) were evaluated for cytotoxic activity on two breast cancer cell lines (MCF-7 and MDA-MB-468). Ligand efficiency and binding mode studies were also done and evaluated for their potentially EGFR inhibitory effects in comparison with imatinib and erlotinib as reference drugs. Among the tested 4-anilinoquinazolines, compound 11 , which contains diethoxy at phenyl ring and morpholino pendants at positions 5 and 7 of the quinazoline ring, demonstrated the most potent biological activity on both cell lines. Our new quinazoline derivatives with different substituents such as cyclic or linear ethers and flour groups may be a promising cytotoxic lead compounds for further anti-breast cancer research.

Evaluation of two Iranian domestic ovine breeds for their pathological findings to gastrointestinal infection of Haemonchus contortus.

The generally warm, moist environmental conditions in the Northwestern Iran are ideal for survival and growth of the egg and larval stages of Haemonchus contortus and other gastrointestinal nematodes (GIN) of sheep and goats.A total of 2,421 animals were slaughtered and examined from July 2010 to July 2011 in Urmia abattoir. In case of sheep, 225 out of 2,421 were positive and prevalence of H. contortus infestation was 9.3 %. Sex wise prevalence of H. contortus in sheep was 33.08 % (76/229) in male and 66.22 % (149/225) in female. The females indicated significantly (P < 0.05) higher prevalence (66.22 %) as compared to males (33.08 %). The highest prevalence was recorded in the spring (April) and the lowest was in summer (July), respectively. On microscopic examination, infiltration of mononuclear cells and eosinophils in gastric glands, periglandular hyperemia and hemorrhage, mucous gland hyperplasia, connective tissue proliferation and necrosis was observed. Also, in mixed abomasal infection with Haemonchus and Ostertagia species, mucosal hyperplasia and increased mucous glands and sometimes cystic glands were seen. Statistical analysis using SPSS software, and Chi-square test, demonstrated a non-significant difference between ages and abomasal PH values of infected and healthy sheep (P < 0.05). But the difference between sexes, seasons and abomasal lesions was significant (P > 0.05).

An overall assessment of circumanal gland adenoma in a terrier mix breed dog.

In September 2012, a 10-year-old, intact male, terrier mix breed dog was evaluated because of multiple, 0.5 to 1.2 cm in diameter, round, intradermal nodules around the anus. It had surgery to excise a firm, painful swelling in the left ventrolateral perianal region and the excision part was observed under light microscopy. The mass spreading in to sub acute was of left hind leg out from the ventro-lateral of anus, 1.2 cm×1 cm/ 0 cm×0.5 cm in size and 125 g in weight. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Significant laboratory data demonstrated microcytic anemia (hemoglobin of 6.4 mg/dL) and normal coagulation times. No remarkable abnormalities were found in the complete blood count and an ionized calcium of 1.91 mmol/L (reference range, 1.1-1.3 mmol/L) was confirmed hypercalcemia. On cytologic and histopathologic examinations, evaluation of the aspirate revealed a prominent population of round-to-polygonal nucleated cells arranged as cohesive groups with isolated individual cells. A mild degree of anisocytosis and anisokaryosis was observed. In addition, smaller reserve type cells, with darker cytoplasm and a higher nucleocytoplasmic ratio. The adenomas generally retain the lobular architecture, but some may contain focal areas of cellular pleomorphism. These changes may suggest malignant transformation and have led to discordant interpretations, the well-developed stroma surrounding the lobules and hepatoid cells was noted. Ulceration, hemorrhage, necrosis and secondary infection with inflammatory cell infiltrates are common. These cytology and histopathology features are consistent with hepatoid gland adenoma.

An overall assessment of circumanal gland adenoma in a terrier mix breed dog

In September 2012, a 10-year-old, intact male, terrier mix breed dog was evaluated because of multiple, 0.5 to 1.2 cm in diameter, round, intradermal nodules around the anus. It had surgery to excise a firm, painful swelling in the left ventrolateral perianal region and the excision part was observed under light microscopy. The mass spreading in to sub acute was of left hind leg out from the ventro-lateral of anus, 1.2 cmí1 cm/ 0 cmí0.5 cm in size and 125 g in weight. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Significant laboratory data demonstrated microcytic anemia (hemoglobin of 6.4 mg/dL) and normal coagulation times. No remarkable abnormalities were found in the complete blood count and an ionized calcium of 1.91 mmol/L (reference range, 1.1-1.3 mmol/L) was confirmed hypercalcemia. On cytologic and histopathologic examinations, evaluation of the aspirate revealed a prominent population of round-to-polygonal nucleated cells arranged as cohesive groups with isolated individual cells. A mild degree of anisocytosis and anisokaryosis was observed. In addition, smaller reserve type cells, with darker cytoplasm and a higher nucleocytoplasmic ratio. The adenomas generally retain the lobular architecture, but some may contain focal areas of cellular pleomorphism. These changes may suggest malignant transformation and have led to discordant interpretations, the well-developed stroma surrounding the lobules and hepatoid cells was noted. Ulceration, hemorrhage, necrosis and secondary infection with inflammatory cell infiltrates are common. These cytology and histopathology features are consistent with hepatoid gland adenoma.