Studies

Induced fit docking studies of the dinitroaniline parent trifluraline and the newly designed dinitroaniline-etherphospholipid hybrids against different potential binding sites in monomeric and multimeric kinetoplastid tubulin receptors.

Sequence and electrostatic potential analyses to identify sites in tubulins that differ between dinitroaniline-sensitive and dinitroaniline-resistant species.

Computational prediction of physicochemical and advanced descriptors related to ADME-Tox and PAINS assessment. Potential correlations of the computed descriptors with experimentally determined anti-parasitic activities and correlations between experimentally determined levels of target protein inhibition (PTR1, DHFR) with the anti-parasitic activity were also studied.

Rigid-body docking studies and induced-fit docking studies of pteridine-based compounds to the target proteins TbPTR1, TbDHFR, LmPTR1, LmDHFR and the off-target hDHFR. For both PTR1 variants and human DHFR, conserved structural water sets were considered. Preparations of compound libraries and docking receptors are also covered.