title: In vitro growth inhibitory efficacy of some target specific novel drug molecules against Theileria equi.
abstract: The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory 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 μM, 14.00 μM, 246.34 μM and 0.279 μM (equivalent to 0.139 μg/ml), respectively (P<0.05). The andrographolide was not effective in inhibiting in vitro growth of T. equi in the present study. Furthermore, the in vitro cytotoxicity of these five drugs was evaluated on horse PBMC. At 2000 μM 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, HHD was having low IC50 value along with least cytotoxicity, as compared to reference drug imidocarb dipropionate. The difference in IC50 value of HDTAB and HHD was significant, but HDTAB was moderately more cytotoxic 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 molecules against T. equi parasite by acting on Hsp90 and choline kinase pathway.
authors.affiliation: National Research Center on Equines, Sirsa Road, Hisar 125 001, Haryana, India; Division of Veterinary Medicine, Indian Veterinary Research Institute, Izatnagar 243 122, Uttra Pradesh, India.
authors.forename: A
authors.initials: A
authors.lastname: Gopalakrishnan
authors.affiliation: National Research Center on Equines, Sirsa Road, Hisar 125 001, Haryana, India.
authors.forename: C
authors.initials: C
authors.lastname: Maji
authors.affiliation: National Research Center on Equines, Sirsa Road, Hisar 125 001, Haryana, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Dahiya
authors.affiliation: National Research Center on Equines, Sirsa Road, Hisar 125 001, Haryana, India; Division of Veterinary Medicine, Indian Veterinary Research Institute, Izatnagar 243 122, Uttra Pradesh, India.
authors.forename: A
authors.initials: A
authors.lastname: Suthar
authors.affiliation: National Research Center on Equines, Sirsa Road, Hisar 125 001, Haryana, India.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.affiliation: National Research Center on Equines, Sirsa Road, Hisar 125 001, Haryana, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Gupta
authors.affiliation: Division of Veterinary Medicine, Indian Veterinary Research Institute, Izatnagar 243 122, Uttra Pradesh, India.
authors.forename: U
authors.initials: U
authors.lastname: Dimri
authors.affiliation: National Research Center on Equines, Sirsa Road, Hisar 125 001, Haryana, India. Electronic address: kumarsanjay66@yahoo.com.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D055808:Drug Discovery; D006736:Horses; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D016794:Theileria / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000981:Antiprotozoal Agents
keywords: Cytotoxicity; Drug molecules; In vitro; MASP; Theileria equi