Synthesis, anti-inflammatory, and structure antioxidant activity relationship of novel 4-quinazoline
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Med Chem Res (2013) 22:4641–4653 DOI 10.1007/s00044-013-0468-9
ORIGINAL RESEARCH
Synthesis, anti-inflammatory, and structure antioxidant activity relationship of novel 4-quinazoline Mohammed Abdalla Hussein
Received: 10 August 2012 / Accepted: 3 January 2013 / Published online: 17 January 2013 Springer Science+Business Media New York 2013
Abstract The practice of medicinal chemistry is devoted to the discovery and development of new agents for treating disease. A new derivative of methyl 2-((E)-3-(3,4dihydroxyphenyl)acrylamido)benzoate 2 was synthesized by reacting the amino group of methyl anthranilate 1 with caffeic acid in the presence of PCl3. Cyclcondensation of 2 with hydrazine hydrate afforded the corresponding 2,3-dihydro-2-(3,4-dihydroxyphenyl) pyrazolo[5,1-b]quinazolin-9(1H)-one 3. The median lethal doses (LD50s) of compounds 2 and 3 in mice were 1,135 and 495 mg/kg b.w., respectively. The anti-inflammatory, reducing power, chelating activity on Fe2?, free radical-scavenging, and total antioxidant activities were more pronounced in compound 2 compared to compound 3. On the other hand, antipyretic activity was more pronounced in compound 3 compared to compound 2. Antioxidant activity of compounds 2 and 3 increased with increased concentrations. Total antioxidant activity of compounds 2, 3 and both standards decreased in the order of a-tocopherol [ compound 2 [ trolox [ BHA [ BHT [ compound 3. Administration of compounds 2 and 3 orally to the rats at dose of 50, 100, and 150 mg/kg b.w., for 10 days showed non-significant changes in serum level of GOT, GPT, ALP, c-GT, and LDH as compared with the control group. In addition, oral administration of the compound 2 at a concentration of 100 and 150 mg/kg b.w. and compound 3 at a concentration of 150 mg/kg b.w. daily to normal rats for 10 days showed a significant increase in liver GSH, GPx,
M. A. Hussein (&) Department of Biochemistry, Faculty of Pharmacy, October 6th University, 6th of October City, Egypt e-mail: [email protected]; [email protected] URL: www.Scitopics.com
GR, and GST activities and significant decrease in TBARS level. But, administration of diclofenac sodium (30 mg/kg b.w.) orally to the rats daily for 10 days to rats showed significant increase in serum SGOT, SGPT, ALP, c-GT, and LDH and significant decrease in liver GSH, GPx, GR, and GST activities. These findings suggest that compounds 2 and 3 exhibited good antioxidant and anti-inflammatory activity and also showed effects on liver enzymes. Keywords Quinazolines Caffeic acid Antioxidant Anti-inflammatory Oxidative stress biomarkers
Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of acute and chronic inflammation, pain, and fever. In medicinal chemistry, quinazolines have been very well known for their therapeutic applications. Quinazolin-ones with 2,3-substitution are reported to possess significant analgesic, anti-inflammatory (AbdelRahman et al., 2003; Chambhare et al., 2003), and anticonvulsan
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