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Tuberculosis (TB) is a global lethal disease caused by Mycobacterium tuberculosis (Mtb). The flavoenzyme decaprenylphosphoryl-β- d -ribose 2′-oxidase (DprE1) plays a crucial part in the biosynthesis of lipoarabinomannan and arabinogalactan for the cell wall of Mtb and represents a promising target for anti-TB drug development. Therefore, there is an urgent need to discover DprE1 inhibitors with novel scaffolds, improved bioactivity and high drug-likeness. Recent studies have shown that artificial intelligence/computer-aided drug design (AI/CADD) techniques are powerful tools in the discovery of novel DprE1 inhibitors. This review provides an overview of the discovery of DprE1 inhibitors and their underlying mechanism of action and highlights recent advances in the discovery and optimization of DprE1 inhibitors using AI/CADD approaches. [ABSTRACT FROM AUTHOR]

Two bianthryl dyads, with the two units connected at either the 2- or 9- positions of the anthryl moiety, were studied to establish the relationship between orientation of the anthryl moieties and the electronic coupling and intersystem crossing (ISC) efficiency. The anthryl moieties in the two dyads adopt a close-to-orthogonal geometry, with dihedral angles of 90° (9,9′-bianthryl) and 106° (2,9′-bianthryl) at the ground state, respectively. The charge transfer (CT) emission efficiency and the fluorescence lifetimes are clearly dependent on the electronic coupling between the two anthryls, and stronger coupling lead to higher fluorescence quantum yields (34% vs. 9%) and shorter luminescence lifetimes (13.9 ns vs. 38.6 ns). The bianthryl with more orthogonal geometry shows higher singlet oxygen quantum yields Φ Δ (9,9′-bianthryl, Φ Δ = 53%) than 2,9′-bianthryl (Φ Δ = 32%). Moreover, highly solvent polarity-dependent fluorescence emission and Φ Δ were observed for the dyads (Φ Δ = 22–53%), which is different from the trend of the monomer anthracene, thus we propose the spin-orbit charge transfer ISC (SOCT-ISC) is responsible for the triplet state productions of the dyads. Interestingly, we found that inducing a heavy atom (Br) does not increase the ISC yield of anthracene. ISC in bianthryls was also confirmed with nanosecond transient absorption spectroscopy, the featured T 1 →T n absorption at ca. 433 nm was observed, and the triplet state lifetime are long (9,9′-bianthryl, τ T = 353 μs; 2,9′-bianthryl, τ T = 493 μs, in acetonitrile). • Efficient solvent-dependent SOCT ISC for bianthryls was observed (Φ Δ = 22%–53%). • Long triplet state lifetime was achieved (τ T = 493 μs). • The triplet states of bianthryls have the feature of charge transfer character. • Orthogonal molecular conformation is beneficial for ISC of bianthryls. [ABSTRACT FROM AUTHOR]