scholarly journals Computational study to discover potent phytochemical inhibitors against drug target, squalene synthase from Leishmania donovani

Heliyon ◽  
2021 ◽  
pp. e07178
Author(s):  
Padmika Madushanka Wadanambi ◽  
Uthpali Mannapperuma
Keyword(s):  
Drug Target ◽  
Leishmania Donovani ◽  
Computational Study ◽  
Squalene Synthase

scholarly journals Cloning, overexpression and characterization of Leishmania donovani squalene synthase

2010 ◽  
Vol 311 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Prachi Bhargava ◽  
Kishore Kumar ◽  
Shailendra S. Chaudhaery ◽  
Anil K. Saxena ◽  
Uma Roy
Keyword(s):  
Leishmania Donovani ◽  
Squalene Synthase

scholarly journals N-Myristoyltransferase from Leishmania donovani: Structural and Functional Characterisation of a Potential Drug Target for Visceral Leishmaniasis

2010 ◽  
Vol 396 (4) ◽  
pp. 985-999 ◽  
Author(s):  
James A. Brannigan ◽  
Barbara A. Smith ◽  
Zhiyong Yu ◽  
Andrzej M. Brzozowski ◽  
Michael R. Hodgkinson ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Drug Target ◽  
Leishmania Donovani ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Functional Characterisation

scholarly journals The Qi Site of Cytochrome b is a Promiscuous Drug Target in Trypanosoma cruzi and Leishmania donovani

2020 ◽  
Vol 6 (3) ◽  
pp. 515-528 ◽  
Author(s):  
Richard J. Wall ◽  
Sandra Carvalho ◽  
Rachel Milne ◽  
Juan A. Bueren-Calabuig ◽  
Sonia Moniz ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cytochrome B ◽  
Drug Target ◽  
Leishmania Donovani

scholarly journals Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase

2020 ◽  
Vol 1 ◽  
Author(s):  
Padmika Wadanambi
Keyword(s):  
Leishmania Donovani ◽  
Neglected Tropical Diseases ◽  
Homology Model ◽  
Leishmania Species ◽  
Vital Role ◽  
Squalene Synthase ◽  
Antileishmanial Activity ◽  
Causative Agents ◽  
Parasite Viability ◽  
Ucsf Chimera

AbstractLeishmania species are the causative agents for Leishmaniasis which is one of the neglected tropical diseases causing 70,000 deaths worldwide each year. Squalene synthase enzyme plays a vital role in sterol metabolism which is essential for Leishmania parasite viability. Therefore squalene synthase of Leishmania donovani is a therapeutic target to inhibit growth of parasite. The 3D model of Leishmania donovani Squalene Synthase (LdSQS) was generated by homology modeling and validated through PROCHECK, ERRAT, VERIFY3D and PROSA tools. Virtual screening of the protein was performed by AutoDock with reported inhibitor, E5700 and two natural alkaloids. Molecular interactions were explored to understand the nature of intermolecular bonds between active ligand and the protein binding site residues using UCSF Chimera and PLIP server. The reported inhibitor showed the best binding affinity (-9.75 kcal/mol) closely followed by Ancistrotanzanine B (-9.55 kcal/mol) and Holamine (-8.79 kcal/mol). Ancistrotanzanine B showed low binding energy and permissible ADMET properties. Based on the present study, homology model of LdSQS and Ancistrotanzanine B can be used to design inhibitors with antileishmanial activity.

Cloning, expression, characterization and inhibition studies on trypanothione synthetase, a drug target enzyme, from Leishmania donovani

2011 ◽  
Vol 392 (12) ◽  
pp. 1113-1122 ◽  
Author(s):  
Prakash Saudagar ◽  
Vikash Kumar Dubey
Keyword(s):  
Gene Cloning ◽  
Drug Target ◽  
Leishmania Donovani ◽  
Redox Homeostasis ◽  
Substrate Inhibition ◽  
Leishmanicidal Activity ◽  
High Substrate ◽  
Glutathione Concentration ◽  
Expression Characterization ◽  
Inhibition Studies

Abstract Trypanothione synthetase, a validated drug target, synthesizes trypanothione from glutathione and spermidine. Here we report the gene cloning, expression, characterization and inhibition studies of trypanothione synthetase from Leishmania donovani (LdTryS). The purified recombinant LdTryS enzyme obeyed Michaelis-Menten kinetics. High substrate inhibition was observed with glutathione (Km=33.24 μm, kcat=1.3 s-1, Ki=866 μm). The enzyme shows simple hyperbolic kinetics with fixed glutathione concentration and with other substrates limiting Km values for Mg. ATP and spermidine of 14.2 μm and 139.6 μm, respectively. LdTryS was also screened for inhibitors. Tomatine, conessine, uvaol and betulin were identified as inhibitors of the enzyme and were tested for leishmanicidal activity. Finally, the effect of LdTryS inhibitors on redox homeostasis of the parasite gives a broader picture of their action against leishmaniasis.

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