Discovery of novel DprE1 inhibitors via computational bioactivity fingerprints and structure-based virtual screening

Recent Advances of DprE1 Inhibitors against Mycobacterium tuberculosis: Computational Analysis of Physicochemical and ADMET Properties

“…To investigate the molecular diversity and ADMET properties of the DprE1 inhibitors disclosed in this review, we collected a data set of a total of 1519 structurally diverse molecules by reviewing the literature from the year 2009 to April 2022. − ,− …”

“…Numerous scaffolds acting noncovalently also have been investigated for their activity against Mtb and are depicted in Table . These inhibitors include non-nitro BTZ analogues (NC BTZ), − benzothiazoles (BTO), , 1,2,3-triazole-2-mercaptobenzothiazoles (2-S-BTO), 1,4-azaindoles (AZA), − benzimidazoles (BI), pyrazolopyridones (PP), 4-aminoquinolone piperidine amides (4-AQ), 2-carboxyquinoxaline derivatives (2-CQ), pyrrolothiadiazoles (PTD), , morpholine-pyrimidines (MP), N -alkyl-5-hydroxypyrimidinone carboxamides (NAHPC), , hydantoins (HYD), , benzodioxanes (BD), 3,4-dihydrocarbostyril derivatives (CD), − thiophene-arylamide compounds (TPA), N -(4-hydroxy-3-mercaptonaphthalenyl) sulfonamides (NHMS), and avermectins (AVMT) …”

MetalProGNet: a structure-based deep graph model for metalloprotein–ligand interaction predictions

“…1 Computational methods, such as molecular docking and machine learning (ML)-based approaches, provide an effective and low-cost way to identify the potential binding ligands of a protein target. [7][8][9][10][11] To date, versatile docking programs have been accessible, including traditional ones [12][13][14][15][16][17][18][19][20] and deep learning-based ones. [21][22][23] However, only a few of them, such as FlexX, 24 AutoDock Zn , 25 MpsDock Zn 26 and GM-Dock Zn , 27 are specially developed for metalloproteins due to the intricate coordination geometries derived from metal ions, and most of them are predominantly specic to zinc metalloproteins.…”

Discovery of N-(1-(6-Oxo-1,6-dihydropyrimidine)-pyrazole) Acetamide Derivatives as Novel Noncovalent DprE1 Inhibitors against Mycobacterium tuberculosis

“…16 Recently, our group reported a covalent DprE1 inhibitor that could kill Mtb in vitro (H3, MIC Mtb = 1.25 μM) identified through computational bioactivity fingerprints and structure-based VS, which provides a basis for further explorations. 17 In this study, an integrated computer-aided drug design (CADD) strategy, which integrated molecular docking, drug like analysis, and binding free energy calculation, was employed to identify potential DprE1 inhibitors. Msm was used as the model strain to preliminarily evaluate the antimycobacterial activity, and compound LK-33 was successfully identified.…”

“…Compound 50 exhibited anti-TB activity with a MIC Mtb of 9.75 μM in vitro . Recently, our group reported a covalent DprE1 inhibitor that could kill Mtb in vitro ( H3, MIC Mtb = 1.25 μM) identified through computational bioactivity fingerprints and structure-based VS, which provides a basis for further explorations …”