Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 52878675X | ||
| 005 | 20190715031132.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924e20180808xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000290645 |2 doi |
| 024 | 7 | 0 | |a 10.1038/s42004-018-0043-x |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/290645 | ||
| 245 | 0 | 0 | |a Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity |h [Elektronische Daten] |c [Francesca Grisoni, Daniel Merk, Viviana Consonni, Jan Alexander; id_orcid 0000-0003-0559-4330 Hiss, Sara Giani Tagliabue, Roberto Todeschini, Gisbert; id_orcid 0000-0001-6706-1084 Schneider] |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a Natural products offer unexplored molecular frameworks for the development of chemical leads and innovative drugs. However, the structural complexity of natural products compared with synthetic drug-like molecules often limits the scaffold hopping potential of natural-product-inspired molecular design. Here we introduce a holistic molecular representation incorporating pharmacophore and shape patterns, which facilitates scaffold hopping from natural products to isofunctional synthetic compounds. This computational approach captures simultaneously the partial charge, atom distributions and molecular shape. In a prospective application, we use four natural cannabinoids as queries in a chemical database search for novel synthetic modulators of human cannabinoid receptors. Of the synthetic compounds selected by the new method, 35% are experimentally confirmed as active. These cannabinoid receptor modulators are structurally less complex than their respective natural product templates. The results of this study validate this holistic molecular representation for hit and lead finding in drug discovery. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Grisoni |D Francesca |e joint author | |
| 700 | 1 | |a Merk |D Daniel |e joint author | |
| 700 | 1 | |a Consonni |D Viviana |e joint author | |
| 700 | 1 | |a Hiss |D Jan Alexander; id_orcid 0000-0003-0559-4330 |e joint author | |
| 700 | 1 | |a Tagliabue |D Sara Giani |e joint author | |
| 700 | 1 | |a Todeschini |D Roberto |e joint author | |
| 700 | 1 | |a Schneider |D Gisbert; id_orcid 0000-0001-6706-1084 |e joint author | |
| 773 | 0 | |t Communications Chemistry |d London : Macmillan Publishers |g 1 (1), p. 44 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/290645 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/290645 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Grisoni |D Francesca |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Merk |D Daniel |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Consonni |D Viviana |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Hiss |D Jan Alexander; id_orcid 0000-0003-0559-4330 |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Tagliabue |D Sara Giani |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Todeschini |D Roberto |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schneider |D Gisbert; id_orcid 0000-0001-6706-1084 |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t Communications Chemistry |d London : Macmillan Publishers |g 1 (1), p. 44 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||