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.

I n canine practice, many drugs are employed for their anti-inflammatory properties. These drugs might have an impact on hemato-biochemical and hormonal status in the body. Thyroid hormone status is known to be impacted by several factors among them drugs. These drugs working through modification of synthesis/secretion or have a direct influence on "hypothalamic-pituitary-thyroid Axis"; GCs -Exogenous or Endogenous-were known to influence thyroid hormones in dogs (Daminet and Ferguson, 2003; Nelson and Maggiore, 2020). Glucocorticoids (GCs), an anti-inflammatory and immunosuppressive drug, used extensively in veterinary settings (Andrade et al., 2018). They were classified according to their effect on inflammation into rapid, intermediate, and long-acting (Torres et al., 2005). Numerous conditions benefit from GCs; either as an acute therapy, for instance: allergies, asthma, dermatologic conditions (allergic dermatoses, pemphigus) or as a chronic therapy: adrenal insufficiency, acquired thrombocytopenia, many inflammatory and neoplastic conditions (Plumb, 2018; Narang and Singh Preet, 2019). GCs have minimal effect on hematology (Bhavani et al., 2015) and varied hepatic enzymes activities alterations (Hinson et al., 2010).Dexamethasone, a synthetic GCs, is known for its potency which was approximated to be about 5-10 times the potency of prednisolone (Derendorf et al., 1993; Andrade et al., 2018). Several studies showed the effect of anti-in-research Article Abstract | Veterinary drug formulary includes many anti-inflammatory drugs, among them Glucocorticoids (GCs). This study evaluated the influence of dexamethasone parenterally (IM) on hematology, biochemistry, thyroid function in normal healthy dogs. Ten mongrel dogs were enrolled in this study, each dog received dexamethasone at a dose of 0.1 mg/kg once daily for 7 days then on an alternate day for 14 days. Blood samples were taken at day 0, day 7, and day 21 of the experiment for determination of CBC, ALT, ALP, Cholesterol, Serum total thyroxine (T4), free T4 (fT4), and thyroid-stimulating hormone (TSH). No significant changes in hematology were recorded throughout the experimental period. Elevation of ALT and ALP was recorded on day 7 and continue on day 21. Total T4 decreased significantly at day 7 and day 21. Free T4 showed a non-significant decrease at day 7 and day 21 compared to day 0 values, TSH showed a non-significant decrease at day 7, however, at day 21, TSH values were elevated to the level of day 0. Dexamethasone administration has an impact on the enzymatic activities of the liver. Administration of dexamethasone at a dosage of 0.1 mg /kg once daily for 7 days decreased total T4, while fT4 was unchanged, suggesting that fT4 may be less affected by daily dexamethasone administration. Administration of dexamethasone every other day meddled with TT4 but its effect on FT4 was minimum. Dexamethasone in this administrated dose has a little effect on serum TSH value.

Microbial DNA gyrase is regarded as an outstanding microbial target. Hence, 15 new quinoline derivatives (5–14) were designed and synthesized. The antimicrobial activity of the afforded compounds was pursued via in vitro approaches. The investigated compounds displayed eligible MIC values, particularly against G-positive Staphylococcus aureus species. Consequently, an S. aureus DNA gyrase supercoiling assay was performed, using ciprofloxacin as a reference control. Obviously, compounds 6b and 10 unveiled IC50 values of 33.64 and 8.45 μM, respectively. Alongside, ciprofloxacin exhibited an IC50 value of 3.80 μM. Furthermore, a significant docking binding score was encountered by compound 6b (−7.73 kcal/mol), surpassing ciprofloxacin (−7.29 kcal/mol). Additionally, both compounds 6b and 10 revealed high GIT absorption without passing the blood brain barrier. Finally, the conducted structure−activity relationship study assured the usefulness of the hydrazine moiety as a molecular hybrid for activity either in cyclic or opened form.

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