Synthesis and anti-hyperlipidemic activity of 3H-benzo [4, 5] thieno [2, 3-d] [1, 2, 3] triazin-4-ones: possible mechanism of altered lipid metabolism

ABSTRACT

The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 [3-[methyl]-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one], CP-2 [3-[ethyl]- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one] and CP-6 [3-[2-chloro phenyl]-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one] against dexamethasone and Triton WR-1339-induced hyper- lipidemia in rats. Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone [10 mg/kg, subcutaneous [s.c.]] and Triton WR-1339 [200 mg/kg, intraperitoneal [i.p]] induced hyperlipidemia in rats. Administration of single dose of Triton WR-1339 [200 mg/kg i.p] and dexamethasone [10 mg/kg s.c.] for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compare to normal control. Pretreatment with Atorvastatin [10 mg/kg, p.o.], CP-1 [25 and 50 mg/kg], CP-2 [25 and 50 mg/kg] and CP-6 [25 and 50 mg/kg] showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2. These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia