Small molecule libraries for virtual screening are becoming a well-established tool for the identification of new hit compounds. As for experimental assays, the library quality, defined in terms of structural complexity and diversity, is crucial to increase the chance of a successful outcome in the screening campaign. In this context, Diversity-Oriented Synthesis has proven to be very effective, as the compounds generated are structurally complex and differ not only for the appendages, but also for the molecular scaffold. In this work, we automated the design of a library of lactams by applying a Diversity-Oriented Synthesis strategy called Build/Couple/Pair. We evaluated the novelty and diversity of these compounds by comparing them with lactam moieties contained in approved drugs, natural products, and bioactive compounds from ChEMBL. Finally, depending on their scaffold we classified them into β-, γ-, δ-, ε-, and isolated, fused and spiro- lactam groups and we assessed their drug-like and lead-like properties, thus providing the valence of this novel in silico designed library for medicinal chemistry applications.

Computational-aided design of a library of lactams through a Diversity-Oriented Synthesis strategy / Saldívar-González, Fernanda I.; Lenci, Elena; Calugi, Lorenzo; Medina-Franco, José L.; Trabocchi, Andrea. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - ELETTRONICO. - 28(2020), pp. 115539-115539. [10.1016/j.bmc.2020.115539]

Computational-aided design of a library of lactams through a Diversity-Oriented Synthesis strategy

Lenci, Elena;Calugi, Lorenzo;Trabocchi, Andrea
2020

Abstract

Small molecule libraries for virtual screening are becoming a well-established tool for the identification of new hit compounds. As for experimental assays, the library quality, defined in terms of structural complexity and diversity, is crucial to increase the chance of a successful outcome in the screening campaign. In this context, Diversity-Oriented Synthesis has proven to be very effective, as the compounds generated are structurally complex and differ not only for the appendages, but also for the molecular scaffold. In this work, we automated the design of a library of lactams by applying a Diversity-Oriented Synthesis strategy called Build/Couple/Pair. We evaluated the novelty and diversity of these compounds by comparing them with lactam moieties contained in approved drugs, natural products, and bioactive compounds from ChEMBL. Finally, depending on their scaffold we classified them into β-, γ-, δ-, ε-, and isolated, fused and spiro- lactam groups and we assessed their drug-like and lead-like properties, thus providing the valence of this novel in silico designed library for medicinal chemistry applications.
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115539
115539
Goal 3: Good health and well-being
Saldívar-González, Fernanda I.; Lenci, Elena; Calugi, Lorenzo; Medina-Franco, José L.; Trabocchi, Andrea
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1193268
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