L.Sutharson
Department of Pharmacology Aditya Bangalore Institute Of Pharmacy Education And Research,12-Kogilu Main Road,Yelahanka,Bangalore-64,India

Abstract:

Oxazolone play a vital role in the manufacturing of various biologically active drugs like analgesic, anti-inflammatory, anti-depressant, anti-cancer, anti-microbial, anti-diabetic and anti-obesity drugs. Hence in this research we have screened acute and sub-acute toxicity studies of some newer synthetic 2-phenyl oxazol-5-one derivatives which were obtained from the Department of Pharmaceutical chemistry, Himalayan Pharmacy Institute, Sikkim, INDIA.

OXZ1:4-[3-chloro-benzylidine]-2-phenyl oxazol-5-one, OXZ2: 4-[2-nitro-benzylidine]-2-phenyl oxazol-5-one, OXZ3: 4-[furfurylidine]-2-phenyl oxazol-5-one, OXZ4: 4-[3, 4-dimethoxy-benzylidine]-2-phenyl oxazol-5-one and OXZ5: 4-[2-hydroxy-3-methoxy-benzylidine]-2-phenyl oxazol-5-one are the newer synthetic derivatives under taken for Toxicity studies. OXZ derivatives were shown LD50 >5000mg/kg in the acute oral toxicity studies by OECD guideline-425. Anti-inflammatory activity was performed by carrageenan (0.1ml of 1%w/v) induced paw edema on rats and the paw volume was measured with the help of Digital Paw edema meter ( Model 521 IITC Life sciences, USA) at 1hr interval up to 4hrs after drug administration. OXZ derivatives were administered at the doses of 200 and 400mg/kg p.o before 30 minutes of phlogistc induction. OXZ3 was shown to have potent (**P<0.01compared to vehicle control) anti-inflammatory activity compared to other derivatives. Therefore OXZ3 was chosen for sub-acute toxicity study by OECD TG 407 [Repeated Dose 28-day oral toxicity study in rodents] guideline. Hematological parameter of OXZ3 treated rats have not shown any significant changes compared to control. In biochemical analysis the level of AST, ALT and serum glucose were slightly elevated in 1000mg/kg treated rats. Histo-pathological studies revealed OXZ3 1000mg/kg,p.o treated rats shown slight elongation of sinusoids and nucleatic vacuolation in liver and slight destruction of tubular cells and atrophied glomeruli of kidney where as cardiac tissue had not shown any pathological changes.

In nutshell, this preclinical research work provided the outcome of OXZ3:4-[furfurylidine]-2-phenyl oxazol-5-one is a source of anti-inflammatory drug with minimal toxicities. Profound toxicological studies are required in animals to assess the safety of this molecule before entering clinical research