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

2021 ◽  
pp. 101696
Author(s):  
A. Suthar ◽  
C. Maji ◽  
A. Gopalkrishnan ◽  
S.H. Raval ◽  
R. Kumar ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Theileria Equi ◽  
Babesia Caballi

scholarly journals Anti-piroplasmic Activity of Novobiocin as Heat Shock Protein 90 Inhibitor Against in-vitro Cultured Theileria Equi and Babesia Caballi Parasites

2020 ◽  
Author(s):  
Abhinav Suthar ◽  
Chinmoy Maji ◽  
A. Gopalakrishnan ◽  
S. H. Raval ◽  
Rajender Kumar ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Haemolytic Activity ◽  
Mice Model ◽  
Theileria Equi ◽  
Babesia Caballi ◽  
Imidocarb Dipropionate ◽  
Very High

Abstract 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 efficacy 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 identified methods. Results: IC50 (50 % Inhibitory concentration) value of novobiocin against T. equi and B. caballi was 165 µM and 84.85 µM, respectively. Novobiocin significantly 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 CC50 (50 %, cytotoxicity concentration) values were 11.628 mM and 261.97 mM. A very high specific selective index (SSI) was also observed 70.47 and 1587 for respective equine PBMCs and RBCs. Organ specific 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 efficacy 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.

In Vitro Formation of Estrogen Receptor-Heat Shock Protein 90 Complexes1

1992 ◽  
Vol 112 (4) ◽  
pp. 535-540 ◽  
Author(s):  
Koichi Inano ◽  
Takehiko Ishida ◽  
Saburo Omata ◽  
Tsuneyoshi Horigome
Keyword(s):  
Estrogen Receptor ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90

scholarly journals A Brain Penetrating Heat-Shock Protein 90 Inhibitor NXD30001 Inhibits Glioblastoma as a Monotherapy or in Combination With Radiation

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Hao Chen ◽  
Jialiang Wang ◽  
Hengli Tian
Keyword(s):  
Stem Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Median Survival ◽  
Therapeutic Potential ◽  
Heat Shock Protein 90 ◽  
Tumor Bearing ◽  
Client Proteins

Abstract INTRODUCTION It has been increasingly recognized that glioblastoma multiforme (GBM) is a highly heterogeneous disease, which is initiated and sustained by molecular alterations in an array of signal transduction pathways. Heat-shock protein 90 (Hsp90) is a molecular chaperone to be critically implicated in folding and activation of a diverse group of client proteins, many of which are key regulators of important glioblastoma biology. METHODS To determine the therapeutic potential of targeting Hsp90 in glioblastoma, we assessed the anti-neoplastic efficacy of NXD30001, a brain-penetrating Hsp90 inhibitor as a monotherapy or in combination with radiation, both in Vitro and in Vivo. RESULTS Our results demonstrated that NXD30001 potently inhibited neurosphere formation, growth and survival of CD133 + glioblastoma stem cells (GSCs) with the half maximal inhibitory concentrations (IC50) at low nanomolar concentrations. At suboptimal concentrations, inhibition of Hsp90 did not exert cytotoxic activity but rather increased radiosensitivity in GSCs. CD133- GBM cells were less sensitive and not radiosensitized by NXD30001. In lines with its cytotoxic and radiosensitizing effects, NXD30001 dose-dependently decreased phosphorylation protein levels of multiple Hsp90 client proteins, including those playing key roles in GSCs, such as EGFR, Akt, c-Myc, and Notch1. In addition, combining NXD30001 with radiation could impair DNA damage response and ER stress response to induce apoptosis of GSCs. Treatment of orthotopic glioblastoma tumors with NXD30001 extended median survival of tumor-bearing mice by approximately 20% (treated 37 days vs vehicle 31 d, P = .0026). Radiation alone increased median survival of tumor-bearing mice from 31 to 38 d, combination with NXD30001 further extended survival to 43 d (P = .0089). CONCLUSION Our results suggest that GBM stem cells (CD133+) are more sensitive to NXD30001 than non-stem GBM cells (CD133-). Furthermore, combination NXD30001 with radiation significantly inhibits GBM progression than use it as a monotherapy by targeting GSCs.

scholarly journals Potent Antitrypanosomal Activities of Heat Shock Protein 90 Inhibitors In Vitro and In Vivo

2013 ◽  
Vol 208 (3) ◽  
pp. 489-499 ◽  
Author(s):  
Kirsten J. Meyer ◽  
Theresa A. Shapiro
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90

6-alkylsalicylic acid analogues inhibit in vitro ATPase activity of heat shock protein 90

2010 ◽  
Vol 33 (12) ◽  
pp. 1997-2001 ◽  
Author(s):  
Cheng-Zhu Wu ◽  
An Na Moon ◽  
Oksik Choi ◽  
Sun-Young Kang ◽  
Jung Joon Lee ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Atpase Activity ◽  
Heat Shock Protein 90 ◽  
Alkylsalicylic Acid
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