Synthesis, Molecular Docking and Biological Evaluation As HDAC Inhibitors of Cyclopeptide Mimetics by a Tandem Three-component Reaction and Intramolecular [3+2] Cycloaddition

Overview

Journal Mol Divers

Date 2009 May 29

PMID 19475493

Citations 6

Authors

Tracey Pirali

Valeria Faccio

Riccardo Mossetti

Ambra A Grolla

Simone Di Micco

Giuseppe Bifulco

Armando A Genazzani

Gian Cesare Tron

Affiliations

Soon will be listed here.

Abstract

Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide-alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.

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References

Stote R, Karplus M . Zinc binding in proteins and solution: a simple but accurate nonbonded representation. Proteins. 1995; 23(1):12-31. DOI: 10.1002/prot.340230104. View

Janvier P, Sun X, Bienayme H, Zhu J . Ammonium chloride-promoted four-component synthesis of pyrrolo[3,4-b]pyridin-5-one. J Am Chem Soc. 2002; 124(11):2560-7. DOI: 10.1021/ja017563a. View

Paris M, Porcelloni M, Binaschi M, Fattori D . Histone deacetylase inhibitors: from bench to clinic. J Med Chem. 2008; 51(6):1505-29. DOI: 10.1021/jm7011408. View

Pirali T, Tron G, Zhu J . One-pot synthesis of macrocycles by a tandem three-component reaction and intramolecular [3+2] cycloaddition. Org Lett. 2006; 8(18):4145-8. DOI: 10.1021/ol061782p. View

Biel M, Wascholowski V, Giannis A . Epigenetics--an epicenter of gene regulation: histones and histone-modifying enzymes. Angew Chem Int Ed Engl. 2005; 44(21):3186-216. DOI: 10.1002/anie.200461346. View

Sanner M, Olson A, Spehner J . Reduced surface: an efficient way to compute molecular surfaces. Biopolymers. 1996; 38(3):305-20. DOI: 10.1002/(SICI)1097-0282(199603)38:3%3C305::AID-BIP4%3E3.0.CO;2-Y. View

El Fangour S, Guy A, Despres V, Vidal J, Rossi J, Durand T . Total synthesis of the eight diastereomers of the syn-anti-syn phytoprostanes F1 types I and II. J Org Chem. 2004; 69(7):2498-503. DOI: 10.1021/jo035638i. View

Finnin M, Donigian J, Cohen A, Richon V, Rifkind R, Marks P . Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature. 1999; 401(6749):188-93. DOI: 10.1038/43710. View

Nare B, Allocco J, Kuningas R, Galuska S, Myers R, Bednarek M . Development of a scintillation proximity assay for histone deacetylase using a biotinylated peptide derived from histone-H4. Anal Biochem. 1999; 267(2):390-6. DOI: 10.1006/abio.1998.3038. View

10.

Marks P, Breslow R . Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol. 2007; 25(1):84-90. DOI: 10.1038/nbt1272. View

11.

Park H, Lee S . Homology modeling, force field design, and free energy simulation studies to optimize the activities of histone deacetylase inhibitors. J Comput Aided Mol Des. 2005; 18(6):375-88. DOI: 10.1007/s10822-004-2283-3. View

12.

Wang D, Helquist P, Wiech N, Wiest O . Toward selective histone deacetylase inhibitor design: homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases. J Med Chem. 2005; 48(22):6936-47. DOI: 10.1021/jm0505011. View

13.

Govoni M, Lim H, El-Atmioui D, Menge W, Timmerman H, Bakker R . A chemical switch for the modulation of the functional activity of higher homologues of histamine on the human histamine H3 receptor: effect of various substitutions at the primary amino function. J Med Chem. 2006; 49(8):2549-57. DOI: 10.1021/jm0504353. View

14.

Di Micco S, Terracciano S, Bruno I, Rodriquez M, Riccio R, Taddei M . Molecular modeling studies toward the structural optimization of new cyclopeptide-based HDAC inhibitors modeled on the natural product FR235222. Bioorg Med Chem. 2008; 16(18):8635-42. DOI: 10.1016/j.bmc.2008.08.003. View

15.

Driggers E, Hale S, Lee J, Terrett N . The exploration of macrocycles for drug discovery--an underexploited structural class. Nat Rev Drug Discov. 2008; 7(7):608-24. DOI: 10.1038/nrd2590. View

16.

Sternson S, Wong J, Grozinger C, Schreiber S . Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin. Org Lett. 2002; 3(26):4239-42. DOI: 10.1021/ol016915f. View

17.

Somoza J, Skene R, Katz B, Mol C, Ho J, Jennings A . Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure. 2004; 12(7):1325-34. DOI: 10.1016/j.str.2004.04.012. View

18.

Cafici L, Pirali T, Condorelli F, Del Grosso E, Massarotti A, Sorba G . Solution-phase parallel synthesis and biological evaluation of combretatriazoles. J Comb Chem. 2008; 10(5):732-40. DOI: 10.1021/cc800090d. View

19.

Yoo C, Jones P . Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov. 2006; 5(1):37-50. DOI: 10.1038/nrd1930. View

20.

Maulucci N, Chini M, Di Micco S, Izzo I, Cafaro E, Russo A . Molecular insights into azumamide e histone deacetylases inhibitory activity. J Am Chem Soc. 2007; 129(10):3007-12. DOI: 10.1021/ja0686256. View