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

Gopalakrishnan, A.; Maji, Chinmoy; Dahiya, Rajesh K.; Suthar, Abhinav; Kumar, Rajender; Gupta, Ashok Kumar; Dimri, Umesh; Kumar, Sanjay

doi:10.1016/j.vetpar.2015.12.024

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…In addition, the IC 50 value for T. equi for Draxxin ® is one fold lower than the IC 50 values for imidocarb dipropionate ( Gopalakrishnan et al, 2016 ). Also, the imidocarb dipropionate IC 50 value calculated for B. bigemina using an in vitro assay and reported for the first time in this study, is lower than the value calculated for B. bovis .…”

Section: Discussionmentioning

confidence: 76%

“…equi at 72 h after treatment with diminazene aceturate, imidocarb dipropionate, clofazimine and Draxxin ® . Species IC 50 (nM) B. bovis B. bigemina T. equi Diminazene aceturate ( Rizk et al, 2015 ) 400 ± 190 200 ± 160 770 ± 280 Imidocarb dipropionate *( Nott et al, 1990 ); $ ( Rodriguez and Trees, 1996 ); # ( Gopalakrishnan et al, 2016 ); @ in this study 8.6* $ 0.08 @ 279 # Clofazimine ( Tuvshintulga et al, 2016 ) 4500 ± 300 3000 ± 200 290 ± 30 Draxxin ® 16.7 ± 0.6 (15.4–17.9) a 6.2 ± 0.2 (5.8–6.6) a 2.4 ± 0.1 (2.2–2.6) a a 95% CI. …”

Section: Resultsmentioning

confidence: 99%

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Assessment of Draxxin® (tulathromycin) as an inhibitor of in vitro growth of Babesia bovis, Babesia bigemina and Theileria equi

Silva

Villarino

Knowles

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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Babesia bovis, Babesia bigemina and Theileria equi are worldwide tick-borne hemoprotozoan that cause diseases characterized by fever, anemia, weight loss and abortion. A common feature of these diseases are transition from acute to chronic phases, in which parasites may persist in the host for life, and becoming a reservoir for tick transmission. The live-attenuated vaccines for B. bovis and B. bigemina are not available for worldwide use due to legal restrictions and other concerns such as potential erythrocyte antigen and pathogen contamination, and a vaccine for T. equi is not available. The use of chemotherapeutics is essential to treat and control these diseases, but several studies have shown the development of drug-resistance by these parasites, and safe and effective alternative drugs are needed. Tulathromycin, a macrolide antibiotic, has proven to be effective against a vast range of bacteria and Plasmodium yoelli, a Babesia and Theileria related intra-erythrocytic apicomplexan. Draxxin® (tulathromycin) is currently licensed to treat infections that cause respiratory diseases in cattle in several countries. In this study, the activity of Draxxin® was tested in vitro on cultured B. bovis, B. bigemina and T. equi. Addition of the drug to in vitro cultures resulted in cessation of parasite replication of the three species tested, B. bovis, B. bigemina and T. equi, with estimated IC50 of 16.7 ± 0.6 nM; 6.2 ± 0.2 nM and 2.4 ± 0.1 nM, respectively, at 72 h. Furthermore, neither parasites nor parasite DNA were detectable in cultures treated with IC100, suggesting Draxxin® is a highly effective anti-Babesia/Theileria drug. Importantly, the IC50 calculated for Draxxin® for the Babesia/Theileria parasites tested is lower that the IC50 calculated for some drugs currently in use to control these parasites. Collectively, the data strongly support in vivo testing of Draxxin® for the treatment of bovine babesiosis and equine piroplasmosis.

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Section: Discussionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Assessment of Draxxin® (tulathromycin) as an inhibitor of in vitro growth of Babesia bovis, Babesia bigemina and Theileria equi

Silva

Villarino

Knowles

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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“…Various other chemotherapeutic agents have been reported to be potentially used against EP, with variable efficacy, mostly in vitro. Among these are anti-malaria compounds [37][38][39], antimicrobial agents [40][41][42][43][44][45], parasite metabolism inhibitors [34,[46][47][48][49][50][51][52][53], replication inhibitors [54,55], pyrimidine synthesis inhibitors [56,57], and various plant-derived compounds [58][59][60][61][62][63]. However, most of these options have never been tested in vivo, and none is widely used.…”

Section: Immunity Treatment and Controlmentioning

confidence: 99%

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

et al. 2020

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Equine piroplasmosis (EP), caused by the hemoparasites Theileria equi, Theileria haneyi, and Babesia caballi, is an important tick-borne disease of equines that is prevalent in most parts of the world. Infection may affect animal welfare and has economic impacts related to limitations in horse transport between endemic and non-endemic regions, reduced performance of sport horses and treatment costs. Here, we analyzed the epidemiological, serological, and molecular diagnostic data published in the last 20 years, and all DNA sequences submitted to GenBank database, to describe the current global prevalence of these parasites. We demonstrate that EP is endemic in most parts of the world, and that it is spreading into more temperate climates. We emphasize the importance of using DNA sequencing and genotyping to monitor the spread of parasites, and point to the necessity of further studies to improve genotypic characterization of newly recognized parasite species and strains, and their linkage to virulence.

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“…In-vitro cytotoxicity assay on equine PBMCs Cytotoxicity of each concentration of drug molecules was analysed on peripheral blood mononuclear cells (PBMCs) by resazurin-based cell viability assay [8]. Brie y, freshly collected equine PBMCs were suspended in 1 ml complete growth medium consisting of RPMI-1640 supplemented with 2 mM Lglutamine, 60 µg/ml penicillin, 100 µg/ml streptomycin and 10% foetal bovine serum (Sigma Aldrich, India).…”

Section: In-vitro Viability Testmentioning

confidence: 99%

Anti-piroplasmic activity of novobiocin as heat shock protein 90 inhibitor against in vitro cultured Theileria equi and Babesia caballi parasites

Suthar

Maji

Gopalkrishnan

et al. 2021

Ticks and Tick-borne Diseases

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Background: Theileria equi and Babesia caballi are the causative agents for equine piroplasmosis (EP). Currently, imidocarb dipropionate (ID) is the only available drug for treating clinical form of EP. Serious side effects and uncompleted clearance of infection is major drawback of ID. Heat-shock proteins (HSP) play a vital role in the life cycle of these haemoprtozoa by way of preventing alteration in protein conformation. These HSPs are activated during transfer of EP sporozoites from tick vector (poikilotherm) to natural host (homeotherm) and helped it for survival. In this present study we have targeted the heat shock protein 90 pathway of T. equi and B. caballi by its inhibitor drug -novobiocin.Methods: Dose-dependent e cacy of novobiocin drug was observed on growth of T. equi and B. caballi in in-vitro culture. Cell cytotoxicity on host peripheral mononuclear cells (PBMCs) was also checked with different concentration of novobiocin. It was also checked for its haemolytic activity on equine erythrocyte (RBCs) by standard technique. In-vivo organ toxicity of novobiocin was also assessed in mice model with identi ed methods. Results: IC 50 (50 % Inhibitory concentration) value of novobiocin against T. equi and B. caballi was 165 µM and 84.85 µM, respectively. Novobiocin signi cantly arrested the in-vitro growth of T. equi and B. caballi parasites at respective 100 μM and 200 μM drug concentration. In-vitro treated parasites become dead with distorted nuclear material and showed no further viability. The drug was found safe on the equine PBMCs and RBCs cell line even at 1000 µM concentration and CC 50 (50 %, cytotoxicity concentration) values were 11.628 mM and 261.97 mM. A very high speci c selective index (SSI) was also observed 70.47 and 1587 for respective equine PBMCs and RBCs. Organ speci c biochemical markers and histopathological examination indicated no adverse effect of the drug at a dose rate of 50 mg/kg of body weight in mice model. Conclusions:The results clearly indicating the growth inhibitory e cacy of novobiocin against T. equi and B. caballi parasites and its safety on host cell lines with very high SI. Hence, it can be inferred that Theileria/Babesia Hsp-90 family are the potential drug targets worthy of further investigation.

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

Cited by 13 publications

References 31 publications

Assessment of Draxxin® (tulathromycin) as an inhibitor of in vitro growth of Babesia bovis, Babesia bigemina and Theileria equi

Assessment of Draxxin® (tulathromycin) as an inhibitor of in vitro growth of Babesia bovis, Babesia bigemina and Theileria equi

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

Anti-piroplasmic activity of novobiocin as heat shock protein 90 inhibitor against in vitro cultured Theileria equi and Babesia caballi parasites

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