scholarly journals Scaffold hopping from synthetic RXR modulators by virtual screening and de novo design

MedChemComm ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 1289-1292 ◽  
Author(s):  
Daniel Merk ◽  
Francesca Grisoni ◽  
Lukas Friedrich ◽  
Elena Gelzinyte ◽  
Gisbert Schneider
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
De Novo ◽  
De Novo Design ◽  
Scaffold Hopping ◽  
Bioactive Natural Products

The concept of virtual screening and automated de novo design has been corroborated as a viable strategy for scaffold hopping from bioactive natural products to isofunctional, synthetically accessible mimetics.

scholarly journals Structure-Based Virtual Screening and De Novo Design of PIM1 Inhibitors with Anticancer Activity from Natural Products

2021 ◽  
Vol 14 (3) ◽  
pp. 275
Author(s):  
Hwangseo Park ◽  
Jinwon Jeon ◽  
Kewon Kim ◽  
Soyeon Choi ◽  
Sungwoo Hong
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Binding Free Energy ◽  
De Novo Design ◽  
Breast Cancer Cell Lines ◽  
Free Energy Function ◽  
Pim1 Kinase ◽  
Starting Point

Background: the proviral insertion site of Moloney murine leukemia (PIM) 1 kinase has served as a therapeutic target for various human cancers due to the enhancement of cell proliferation and the inhibition of apoptosis. Methods: to identify effective PIM1 kinase inhibitors, structure-based virtual screening of natural products of plant origin and de novo design were carried out using the protein–ligand binding free energy function improved by introducing an adequate dehydration energy term. Results: as a consequence of subsequent enzyme inhibition assays, four classes of PIM1 kinase inhibitors were discovered, with the biochemical potency ranging from low-micromolar to sub-micromolar levels. The results of extensive docking simulations showed that the inhibitory activity stemmed from the formation of multiple hydrogen bonds in combination with hydrophobic interactions in the ATP-binding site. Optimization of the biochemical potency by chemical modifications of the 2-benzylidenebenzofuran-3(2H)-one scaffold led to the discovery of several nanomolar inhibitors with antiproliferative activities against human breast cancer cell lines. Conclusions: these new PIM1 kinase inhibitors are anticipated to serve as a new starting point for the development of anticancer medicine.

scholarly journals In Silico De Novo Curcuminoid Derivatives From the Compound Library of Natural Products Research Laboratories Inhibit COVID-19 3CLpro Activity

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2095326
Author(s):  
Jai-Sing Yang ◽  
Jo-Hua Chiang ◽  
Shih‑Chang Tsai ◽  
Yuan-Man Hsu ◽  
Da-Tian Bau ◽  
...  
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
Binding Affinity ◽  
High Throughput ◽  
In Silico ◽  
De Novo ◽  
Compound Library ◽  
Therapeutic Success ◽  
High Throughput Virtual Screening

The coronavirus disease 2019 (COVID‐19) outbreak caused by the 2019 novel coronavirus (2019-nCOV) is becoming increasingly serious. In March 2019, the Food and Drug Administration (FDA) designated remdesivir for compassionate use to treat COVID-19. Thus, the development of novel antiviral agents, antibodies, and vaccines against COVID-19 is an urgent research subject. Many laboratories and research organizations are actively investing in the development of new compounds for COVID-19. Through in silico high-throughput virtual screening, we have recently identified compounds from the compound library of Natural Products Research Laboratories (NPRL) that can bind to COVID-19 3Lpro polyprotein and block COVID-19 3Lpro activity through in silico high-throughput virtual screening. Curcuminoid derivatives (including NPRL334, NPRL339, NPRL342, NPRL346, NPRL407, NPRL415, NPRL420, NPRL472, and NPRL473) display strong binding affinity to COVID-19 3Lpro polyprotein. The binding site of curcuminoid derivatives to COVID-19 3Lpro polyprotein is the same as that of the FDA-approved human immunodeficiency virus protease inhibitor (lopinavir) to COVID-19 3Lpro polyprotein. The binding affinity of curcuminoid derivatives to COVID-19 3Lpro is stronger than that of lopinavir and curcumin. Among curcuminoid derivatives, NPRL-334 revealed the strongest binding affinity to COVID-19 3Lpro polyprotein and is speculated to have an anti-COVID-19 effect. In vitro and in vivo ongoing experiments are currently underway to confirm the present findings. This study sheds light on the drug design for COVID-19 3Lpro polyprotein. Basing on lead compound development, we provide new insights on inhibiting COVID-19 attachment to cells, reducing COVID-19 infection rate and drug side effects, and increasing therapeutic success rate.

Virtual Screening for Bioactive Molecules by Evolutionary De Novo Design

2000 ◽  
Vol 39 (22) ◽  
pp. 4130-4133 ◽  
Author(s):  
Gisbert Schneider ◽  
Odile Clément-Chomienne ◽  
Laurence Hilfiger ◽  
Petra Schneider ◽  
Stefan Kirsch ◽  
...  
Keyword(s):  
Virtual Screening ◽  
De Novo ◽  
De Novo Design ◽  
Bioactive Molecules

The use of ligand-based de novo design for scaffold hopping and sidechain optimization: Two case studies

2008 ◽  
Vol 16 (1) ◽  
pp. 422-427 ◽  
Author(s):  
Miklos Feher ◽  
Yinghong Gao ◽  
J. Christian Baber ◽  
William A. Shirley ◽  
John Saunders
Keyword(s):  
Case Studies ◽  
De Novo ◽  
De Novo Design ◽  
Scaffold Hopping

Scaffold-Hopping Potential of Fragment-Based De Novo Design: The Chances and Limits of Variation

2009 ◽  
Vol 12 (4) ◽  
pp. 383-396 ◽  
Author(s):  
Bjoern Krueger ◽  
Axel Dietrich ◽  
Karl-Heinz Baringhaus ◽  
Gisbert Schneider
Keyword(s):  
De Novo ◽  
De Novo Design ◽  
Scaffold Hopping

scholarly journals De Novo Design of Potent, Insecticidal Synthetic Mimics of the Spinosyn Macrolide Natural Products

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gary D. Crouse ◽  
David A. Demeter ◽  
Geno Samaritoni ◽  
Casandra L. McLeod ◽  
Thomas C. Sparks
Keyword(s):  
Natural Products ◽  
De Novo ◽  
De Novo Design
Sign in / Sign up

Export Citation Format

Share Document