Cannabis sativa L. chemical compositions as potential plasmodium falciparum dihydrofolate reductase-Thymidinesynthase enzyme inhibitors: An in silico study for drug development

Pham Minh Quan, Le Thi Thuy Huong, Tran Quoc Toan, Nguyen Phi Hung, Pham Hai Nam, Ngo Tuan Kiet, Nguyen Xuan Ha, Dang Thi Thanh Le, Ton Nu Thuy An, Pau Loke Show, Hai Ha Pham Thi

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

This study contributes to anti-malarial research effort by conducting in silico assessment of 125 compounds originated from Cannabis sativa L. against plasmodium falciparum dihydrofolate reductase-Thymidinesynthase (pfDHFR-TS) enzyme for potential inhibition activity. Drug-like and pharmacokinetic criteria were used to assess the drug-like properties of the studied compounds. AutoDock4.2.6 and AutoDock Vina software were used to calculate the possible binding pose of the studied compounds to pfDHFR-TS enzyme. The docking procedure was validated using two known inhibitors cycloguanil and WR99210. 65 out of 125 compounds violated no more than 2 of Lipinski's rule of five and were sorted out as favorable for drug development. Amongst these 65 compounds, pharmacokinetic properties and toxicity evaluation identified 60 compounds that meet the criteria of drug-like properties and were subjected to further docking studies. Docking outcomes identified 10 compounds including compounds 4, 9, 19, 22, 23, 25, 30, 42, 43, and 59 as potential candidates for inhibiting the function of pfDHFR-TS at the active site through hydrogen bonds with Ile14, Asp54, and Ile 164 residues. Compound 9 is considered as the top "hit"with docking energy far more exceeding those of the standard compounds. High correlation coefficient between the docking energy of AutoDock4.2.6 and AutoDock Vina was recorded with the value of R 2 = 0.74.

Original languageBritish English
Pages (from-to)1244-1250
Number of pages7
JournalOpen Chemistry
Volume19
Issue number1
DOIs
StatePublished - 1 Jan 2021

Keywords

  • anti-malarial compounds
  • Cannabis sativa L.
  • molecular docking
  • pfDHFR-TS
  • Plasmodium falciparum
  • virtual screening

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