A Combined Chemical, Computational, and In Vitro Approach Identifies SBL-105 as Novel DHODH Inhibitor in Acute Myeloid Leukemia Cells.

ABSTRACT: Inhibition of the dihydroorotate dehydrogenase (DHODH) has been successful at the preclinical level in controlling myeloid leukemia. However, poor clinical trials warrant the search for new potent DHODH inhibitors. Herein we present a novel DHODH inhibitor SBL-105 effective against myeloid leukemia. Chemical characteristics were identified by ¹H NMR, ¹³C NMR, and mass spectroscopy. Virtual docking and molecular dynamic simulation analysis were performed using the automated protocol with AutoDock-VINA, GROMACS program. Human-recombinant (rh) DHODH was used for enzyme inhibition study. THP-1, TF-1, HL-60, and SKM-1 cell lines were used. MTT assay was used to assess cell viability. Flow cytometry was employed for cell cycle, apoptosis, and differentiation analysis. Chemi

SUBMITTER: Kamli H 

PROVIDER: S-EPMC8790134 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature