The Gramine Route to Pyrido[4,3-b]indol-3-ones - Identification of a New Cytotoxic Lead

Overview

Journal Sci Pharm

Publisher MDPI

Specialty Pharmacology

Date 2011 May 28

PMID 21617772

Citations 3

Authors

Uwe Wollein

Franz Bracher

Affiliations

Soon will be listed here.

Abstract

A novel approach to 3-oxo-γ-carbolines was worked out starting from methyl indol-2-ylacetate via a gramine derivative. After quaternization, ammonia and 4-methoxybenzylamine could be inserted giving appropriate 3-oxo-γ-carbolines. Condensation with 2-chlorobenzaldehyde under microwave irradiation gave a 4-(2-chlorobenzyl)-3-oxo-γ-carboline. N-methylation lead to a product with very promising antifungal and cytotoxic activities.

Citing Articles

Recent Developments of Gramine: Chemistry and Biological Activity.

Zhang J, Jia Q, Li N, Gu L, Dan W, Dai J Molecules. 2023; 28(15).

PMID: 37570664 PMC: 10419902. DOI: 10.3390/molecules28155695.

Design of a new method for the synthesis of novel 2-aryl/alkyl-3H-indol-3-ones.

Akbari A, Seyedi N, Faryabi M Mol Divers. 2022; 28(1):3-9.

PMID: 35715624 DOI: 10.1007/s11030-022-10464-y.

7-Aza-des-A-steroids with Antimicrobial and Cytotoxic Activity.

Krojer M, Keller M, Bracher F Sci Pharm. 2013; 81(2):329-38.

PMID: 23833707 PMC: 3700069. DOI: 10.3797/scipharm.1303-03.

References

Huber K, Schemies J, Uciechowska U, Wagner J, Rumpf T, Lewrick F . Novel 3-arylideneindolin-2-ones as inhibitors of NAD+ -dependent histone deacetylases (sirtuins). J Med Chem. 2009; 53(3):1383-6. DOI: 10.1021/jm901055u. View

Larsen L, Moore R, Patterson G . beta-Carbolines from the blue-green alga Dichothrix baueriana. J Nat Prod. 1994; 57(3):419-21. DOI: 10.1021/np50105a018. View

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

Newman D, Cragg G . Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007; 70(3):461-77. DOI: 10.1021/np068054v. View

Wu J, Wang J, Abeywardane A, Andersen D, Emmanuel M, Gautschi E . The discovery of carboline analogs as potent MAPKAP-K2 inhibitors. Bioorg Med Chem Lett. 2007; 17(16):4664-9. DOI: 10.1016/j.bmcl.2007.05.101. View

Kieburtz K, McDermott M, Voss T, Corey-Bloom J, Deuel L, Ray Dorsey E . A randomized, placebo-controlled trial of latrepirdine in Huntington disease. Arch Neurol. 2010; 67(2):154-60. PMC: 4134015. DOI: 10.1001/archneurol.2009.334. View

Cincinelli R, Cassinelli G, Dallavalle S, Lanzi C, Merlini L, Botta M . Synthesis, modeling, and RET protein kinase inhibitory activity of 3- and 4-substituted beta-carbolin-1-ones. J Med Chem. 2008; 51(24):7777-87. DOI: 10.1021/jm8007823. View

Sun L, Tran N, Tang F, App H, Hirth P, McMahon G . Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J Med Chem. 1998; 41(14):2588-603. DOI: 10.1021/jm980123i. View

Waitzinger J, Lenders H, Pabst G, Reh C, Ulbrich E . Three explorative studies on the efficacy of the antihistamine mebhydroline (Omeril). Int J Clin Pharmacol Ther. 1995; 33(7):373-83. View

10.

Balfour J, Goa K, Perry C . Alosetron. Drugs. 2000; 59(3):511-8; discussion 519-20. DOI: 10.2165/00003495-200059030-00008. View

11.

Ivachtchenko A, Frolov E, Mitkin O, Kysil V, Khvat A, Okun I . Synthesis and biological evaluation of novel gamma-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists. Bioorg Med Chem Lett. 2009; 19(12):3183-7. DOI: 10.1016/j.bmcl.2009.04.128. View

12.

Pezzuto J, Moore P, Hecht S . Metabolic activation of 1-methyl-3-amino-5H-pyrido[4,3-b]indole and several structurally related mutagens. Biochemistry. 1981; 20(2):298-305. DOI: 10.1021/bi00505a011. View

13.

Cao R, Peng W, Wang Z, Xu A . beta-Carboline alkaloids: biochemical and pharmacological functions. Curr Med Chem. 2007; 14(4):479-500. DOI: 10.2174/092986707779940998. View

14.

Wang S, Dong Y, Wang X, Hu X, Liu J, Hu Y . 3-Aryl beta-carbolin-1-ones as a new class of potent inhibitors of tumor cell proliferation: synthesis and biological evaluation. Org Biomol Chem. 2005; 3(5):911-6. DOI: 10.1039/b412921k. View