In vitro growth inhibitory efficacy of some target specific novel drugmolecules against Theileria equi

Abstract

The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated inin vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system wasestablished for propagation of T. equi parasites. This in vitro culture system was used to assess the growthinhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide(HDTAB), hesparidin methyl chalcone (HMC), andrographolide and imidocarb dipropionate against T.equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and imidocarb dipropionate for T.equi growth were 17.42 M, 14.00 M, 246.34 M and 0.279 M (equivalent to 0.139 g/ml), respec-tively (P < 0.05). The andrographolide was not effective in inhibiting in vitro growth of T. equi in thepresent study. Furthermore, the in vitro cytotoxicity of these five drugs was evaluated on horse PBMC. At2000 M concentration of HHD, HDTAB, HMC, andrographolide and imidocarb dipropionate were 8.34,46.44, 58.53, 31.06, 15.14% cytotoxic on PBMC, respectively. Out of our four tested drug molecules, HHDwas having low IC50value along with least cytotoxicity, as compared to reference drug imidocarb dipro-pionate. The difference in IC50value of HDTAB and HHD was significant, but HDTAB was moderately morecytotoxic on PBMC cell lines. HHD and HDTAB are selective inhibitor for heat shock protein 90 (Hsp90)and choline kinase pathway. It can be concluded that HHD and HDTAB are potential drug moleculesagainst T. equi parasite by acting on Hsp90 and choline kinase pathway.