IN SILICO DISCOVERY AND MOLECULAR DOCKING EVALUATION OF NOVEL 3-(TRI FLUORO METHYL) - 5,6,7,8 - TETRA HYDRO –[1,2,4]-TRIAZOLO (4,3-Α)- PYRAZINE (SITAGLIPTIN INTERMIDIATE DERIVATES) INHIBITORS ON E-COLI DNA GYRASE-A

The aim of present investigation is to identify the new potential inhibitors for E. coli DNA Gyrase-A by using in silico and molecular docking. A series of Sitagliptin title compounds were designed and were docked within the “Quinolone Resistance Determining Region” (QRDR) of E. coli DNA Gyrase-A (EcGyr-A) chain (QRDR-A). The obtained docking scores of Sitagliptin intermediate derivatives were compared with score of reference ligand ciprofloxacin and norflaxacin, under identical experimental sets. The Sitagliptin intermediate derivatives (7-(2-Nitrophenylsulfonyl)-3-(trifluoromethyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3,α] pyrazine), showed highest docking score i. e -8.5 kcal.mol-1 , and (7-(4-Chloro-3- nitrophenylsulfonyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo [4,3,α] pyrazine), (7-(4- Flurophenylsulfonyl)-3- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo [4,3,α] pyrazine), (7-(4-Nitrophenylsulfonyl)-3-(trifluoromethyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3,α] pyrazine) and (7-(4-Iodophenylsulfonyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro- [1,2,triazolo[4,3,α] pyrazine) shows moderate docking scores i.e -8.4, -8.0, -7.8 and -7.8 kcal.mol-1 respectively, though the presence of halides at different positions in the parent compound, the sifting position of nitro group from o-p (ortho to para) positions there was great observation of potent inhibitor activity. The results concludes among the tested synthesized analogues selected for docking studies, the compound 6a i.e (7-(2-Nitrophenylsulfonyl)-3-(trifluoromethyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3,α] pyrazine) worked as most potent inhibitor for E. coli DNA Gyrase-A. Keywords: Ciprofloxacin, Docking, DNA Gyrase-A, Norflaxacin, Protein Data Bank, Sitagliptin Intermediate Derivatives