2. Academic Validation
  3. Synthesis, in vitro antiprotozoal activity, molecular docking and molecular dynamics studies of some new monocationic guanidinobenzimidazoles

Synthesis, in vitro antiprotozoal activity, molecular docking and molecular dynamics studies of some new monocationic guanidinobenzimidazoles

  • Eur J Med Chem. 2021 Oct 5:221:113545. doi: 10.1016/j.ejmech.2021.113545.
Fatima Doganc 1,  Ismail Celik 2,  Gokcen Eren 3,  Marcel Kaiser 4,  Reto Brun 4,  Hakan Goker 5
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100, Tandogan, Ankara, Turkey.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, 38280, Yenidogan, Kayseri, Turkey.
  • 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330, Etiler, Ankara, Turkey.
  • 4 Parasite Chemotherapy Unit, Swiss Tropical and Public Health Institute, Basel, CH, 4002, Switzerland; University of Basel, Basel, CH, 4001, Switzerland.
  • 5 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100, Tandogan, Ankara, Turkey. Electronic address: goker@ankara.edu.tr.
PMID: 34091216 DOI: 10.1016/j.ejmech.2021.113545
Abstract

A series of monocationic new guanidinobenzimidazole derivatives were prepared in a four step process starting from 2-nitro-1,4-phenylendiamine. Their antiparasitic activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani were evaluated in vitro. Two out of 20 tested monocationic compounds (7, 14) showed close activity with reference drug chloroquine against P. Falciparum. To understand the interactions between DNA minor groove and in vitro active compounds (7, 14) molecular docking studies were carried out. Stability and binding energies of DNA-ligand complexes formed by DNA with compounds 7 and 14 were measured by molecular dynamics simulations throughout 200 ns time. Root mean square deviation (RMSD) values of the ligands remained stable below 0.25 mm and root mean square fluctuation (RMSF) values of the active site residues with which it interacted decreased compared to the apo form. All compounds exhibited theoretical absorption, distribution, metabolism and excretion (ADME) profiles conforming to Lipinski's and Ghose's restrictive rules.

Keywords

Antiparasitic activity; Molecular docking; Molecular dynamics; Monocationic guanidinobenzimidazoles.

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