Molecular Dynamics Simulation and Docking Studies of Selenocyanate Derivatives as Anti-Leishmanial Agents.
BACKGROUND
Selenocyanate derivatives have been recently presented as potent anti-leishmanial agents.


OBJECTIVE
In this research, thirty five selenocyanate and diselenide compounds were subjected to docking studies and compared to Edelfosine and Miltefosine as reference drugs and then molecular dynamics (MD) simulation analysis.


METHODS
Desired Selenocyanates were built using the HyperChem program and docking calculations were performed on the crystal structure of trypanothione reductase from Leishmania infantum. Then, MD simulation analysis was performed to explore the interaction stability of selected compound during structural motions of the interacting molecules.


RESULTS
Based on the binding energy, all of the aryl rings were more potent than Edelfosine and Miltefosine as reference drug. The best compound base on hydrogen bonding, π-π interactions and orientation within the active site with high binding energy was selected for MD simulation analysis. The selected compound is known as high-affinity selective inhibitor for trypanothione reductase.


CONCLUSIONS
These results can be used for future synthesis of new antileishmanial agents with better potency.
Maryam
M
Iman
Hamid Bakhtiari
HB
Kaboutaraki
Rahim
R
Jafari
Seyed Ayoub
SA
Hosseini
Abolghasem
A
Moghimi
Ali
A
Khamesipour
Asghar Beigi
AB
Harchegani
Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran 19419, Iran; Postal address: No 99, Yakhchal ave. Shariatie Street, Tehran 19419, Iran.. Iran, Islamic Republic of.
Asghar
A
Davood
D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D003485:Cyanates / Q000737:chemistry* / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D018036:Selenium Compounds / Q000737:chemistry* / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D003485:Cyanates; D018036:Selenium Compounds; C053721:selenocyanic acid
Selenocyanate; anti-leishmanial agents; diselenide; docking; molecular dynamics simulations.