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Synthesis, Molecular Docking and Molecular Dynamics Simulation of 2-thioxothiazolidin-4-one derivatives against Gp41

Author(s):

Nahid Tamiz, Tahereh Mostashari-Rad, Aylar Najafipour, Sandra Claes, Dominique Schols and Afshin Fassihi*   Pages 1 - 16 ( 16 )

Abstract:


Introduction: Gp41 and its conserved hydrophobic groove on the N-terminal heptad repeat region are of attractive targets in the design of HIV-1 entry inhibitors. Linearly extended molecules have shown potent anti-HIV-1 activity for their effective interactions with the gp41 binding pocket. Rhodanine ring attached to substituted pyrrole or furan rings has been proved a preferred moiety to be inserted inside the molecular structure of the gp41 inhibitors.

Objectives: Based on the previous findings we are going to describe some rhodanine derivatives in which a substituted imidazole ring is introduced in place of the pyrrole or furan rings. The compounds’ flexibility is increased by inserting methylene groups inside the main scaffold.

Methods: Molecular docking and molecular dynamics simulations approaches were exploited to investigate the chemical interactions and the stability of the designed ligands-gp41 complex. All compounds were synthesized and their chemical structures were elucidated by 1HNMR, 13CNMR, FTIR and Mass spectroscopy. Biological activities of the compounds against HIV-1 and HIV-2 and their cellular toxicities against the T-lymphocyte (MT-4) cell line were determined.

Results: All the designed compounds showed proper and stable chemical interactions with gp41 according to the in silico studies. The results of the biological tests proved none of the compounds active against HIV-1 replication in cell cultures.

Conclusion: Since all the studied compounds were potently toxic for the host cell; it was therefore not possible to assess their anti-HIV activities.

Keywords:

2-thioxothiazolidin-4-one, molecular docking, molecular dynamics simulation, anti-HIV, gp41, synthesis.

Affiliation:

Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan



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