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

• Published in: Veterinary parasitology Vol. 217; pp. 1 - 6
• Main Authors: Gopalakrishnan, A., Maji, C., Dahiya, R.K., Suthar, A., Kumar, R., Gupta, A.K., Dimri, U., Kumar, S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2016
• Subjects: Animals; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Cell Line; Cytotoxicity; Drug Discovery; Drug molecules; Horses; In vitro; In Vitro Techniques; Inhibitory Concentration 50; Leukocytes, Mononuclear - drug effects; MASP; Theileria - drug effects; Theileria - growth & development; Theileria equi; Cytotoxicity; MASP; Drug molecules; Theileria equi; In vitro
• ISSN: 0304-4017; 1873-2550
• DOI: 10.1016/j.vetpar.2015.12.024

•Four target specific drug molecules were tested for Theileria equi in vitro growth inhibitory efficacy.•Harmaline hydrochloride dehydrate specific to Hsp 90 was most effective with IC50 value of 17.42μM.•Hesparidin methyl chalcone and andrographolide anti-oxidatant and nuclear transcription factor-kappaβ inhibitor were least/non-effective.•Hexadecyltrimethylammonium bromide, hesparidin methyl chalcone, andrographolide were more cytotoxic than harmaline hydrochloride dehydrate and imidocarb dipropionate. 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 17.42μM, 14.00μM, 246.34μM and 0.279μM (equivalent to 0.139μg/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 2000μM 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.