Indol-3-ylglyoxylamide As Privileged Scaffold in Medicinal Chemistry

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2023 Jul 29

PMID 37513909

Authors

Elisabetta Barresi

Marco Robello

Emma Baglini

Valeria Poggetti

Monica Viviano

Silvia Salerno

Federico Da Settimo

Sabrina Taliani

Affiliations

Soon will be listed here.

Abstract

In recent years, indolylglyoxylamide-based derivatives have received much attention due to their application in drug design and discovery, leading to the development of a wide array of compounds that have shown a variety of pharmacological activities. Combining the indole nucleus, already validated as a "privileged structure," with the glyoxylamide function allowed for an excellent template to be obtained that is suitable to a great number of structural modifications aimed at permitting interaction with specific molecular targets and producing desirable therapeutic effects. The present review provides insight into how medicinal chemists have elegantly exploited the indolylglyoxylamide moiety to obtain potentially useful drugs, with a particular focus on compounds exhibiting activity in in vivo models or reaching clinical trials. All in all, this information provides exciting new perspectives on existing data that can be useful in further design of indolylglyoxylamide-based molecules with interesting pharmacological profiles. The aim of this report is to present an update of collection data dealing with the employment of this moiety in the rational design of compounds that are able to interact with a specific target, referring to the last 20 years.

Citing Articles

Cheminformatics-Guided Exploration of Synthetic Marine Natural Product-Inspired Brominated Indole-3-Glyoxylamides and Their Potentials for Drug Discovery.

Holland D, Prebble D, Calcott M, Schroder W, Ferretti F, Lock A Molecules. 2024; 29(15).

PMID: 39125052 PMC: 11314621. DOI: 10.3390/molecules29153648.

References

Colley H, Muthana M, Danson S, Jackson L, Brett M, Harrison J . An Orally Bioavailable, Indole-3-glyoxylamide Based Series of Tubulin Polymerization Inhibitors Showing Tumor Growth Inhibition in a Mouse Xenograft Model of Head and Neck Cancer. J Med Chem. 2015; 58(23):9309-33. DOI: 10.1021/acs.jmedchem.5b01312. View

Dorababu A . Indole - a promising pharmacophore in recent antiviral drug discovery. RSC Med Chem. 2021; 11(12):1335-1353. PMC: 8126882. DOI: 10.1039/d0md00288g. View

Meanwell N, Wallace O, Wang H, Deshpande M, Pearce B, Trehan A . Inhibitors of HIV-1 attachment. Part 3: A preliminary survey of the effect of structural variation of the benzamide moiety on antiviral activity. Bioorg Med Chem Lett. 2009; 19(17):5136-9. DOI: 10.1016/j.bmcl.2009.07.027. View

Tantak M, Wang J, Singh R, Kumar A, Shah K, Kumar D . 2-(3'-Indolyl)-N-arylthiazole-4-carboxamides: Synthesis and evaluation of antibacterial and anticancer activities. Bioorg Med Chem Lett. 2015; 25(19):4225-31. PMC: 4567476. DOI: 10.1016/j.bmcl.2015.07.105. View

Kuss H, Hoefgen N, Johanssen S, Kronbach T, Rundfeldt C . In vivo efficacy in airway disease models of N-(3,5-dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281), a selective phosphodiesterase 4 inhibitor for inhaled administration. J Pharmacol Exp Ther. 2003; 307(1):373-85. DOI: 10.1124/jpet.103.053942. View

Primofiore G, Da Settimo F, Taliani S, Simorini F, Patrizi M, Novellino E . N,N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodiazepine receptor. J Med Chem. 2004; 47(7):1852-5. DOI: 10.1021/jm030973k. View

Mehand M, Al-Shorbaji F, Millett P, Murgue B . The WHO R&D Blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts. Antiviral Res. 2018; 159:63-67. PMC: 7113760. DOI: 10.1016/j.antiviral.2018.09.009. View

Alves F, Barreiro E, Fraga C . From nature to drug discovery: the indole scaffold as a 'privileged structure'. Mini Rev Med Chem. 2009; 9(7):782-93. DOI: 10.2174/138955709788452649. View

Akopyants N, Kimblin N, Secundino N, Patrick R, Peters N, Lawyer P . Demonstration of genetic exchange during cyclical development of Leishmania in the sand fly vector. Science. 2009; 324(5924):265-8. PMC: 2729066. DOI: 10.1126/science.1169464. View

10.

Conti M, Jin S . The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol. 1999; 63:1-38. DOI: 10.1016/s0079-6603(08)60718-7. View

11.

Morohaku K, Pelton S, Daugherty D, Butler W, Deng W, Selvaraj V . Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis. Endocrinology. 2013; 155(1):89-97. PMC: 3868810. DOI: 10.1210/en.2013-1556. View

12.

Soni J, Reddy G, Rahman Z, Sharma A, Spandana A, Phanindranath R . Synthesis and cytotoxicity evaluation of DNA-interactive β-carboline indolyl-3-glyoxamide derivatives: Topo-II inhibition and in silico modelling studies. Bioorg Chem. 2022; 131:106313. DOI: 10.1016/j.bioorg.2022.106313. View

13.

Kumar A, Katiyar S, Gupta S, Chauhan P . Syntheses of new substituted triazino tetrahydroisoquinolines and beta-carbolines as novel antileishmanial agents. Eur J Med Chem. 2005; 41(1):106-13. DOI: 10.1016/j.ejmech.2005.09.007. View

14.

Clemett D, Markham A . Linezolid. Drugs. 2000; 59(4):815-27; discussion 828. DOI: 10.2165/00003495-200059040-00007. View

15.

Kaptein S, Vincetti P, Crespan E, Armijos Rivera J, Costantino G, Maga G . Identification of Broad-Spectrum Dengue/Zika Virus Replication Inhibitors by Functionalization of Quinoline and 2,6-Diaminopurine Scaffolds. ChemMedChem. 2018; 13(14):1371-1376. DOI: 10.1002/cmdc.201800178. View

16.

Villalonga-Planells R, Coll-Mulet L, Martinez-Soler F, Castano E, Acebes J, Gimenez-Bonafe P . Activation of p53 by nutlin-3a induces apoptosis and cellular senescence in human glioblastoma multiforme. PLoS One. 2011; 6(4):e18588. PMC: 3071734. DOI: 10.1371/journal.pone.0018588. View

17.

Whiting P . GABA-A receptor subtypes in the brain: a paradigm for CNS drug discovery?. Drug Discov Today. 2003; 8(10):445-50. DOI: 10.1016/s1359-6446(03)02703-x. View

18.

Beesetti H, Tyagi P, Medapi B, Krishna V, Sriram D, Khanna N . A quinoline compound inhibits the replication of dengue virus serotypes 1-4 in Vero cells. Antivir Ther. 2018; 23(5):385-394. DOI: 10.3851/IMP3231. View

19.

Draheim S, Bach N, DILLARD R, Berry D, Carlson D, Chirgadze N . Indole inhibitors of human nonpancreatic secretory phospholipase A2. 3. Indole-3-glyoxamides. J Med Chem. 1996; 39(26):5159-75. DOI: 10.1021/jm960487f. View

20.

Windebank A . Chemotherapeutic neuropathy. Curr Opin Neurol. 1999; 12(5):565-71. DOI: 10.1097/00019052-199910000-00010. View