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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Hologram quantitative structure-activity relationship and comparative molecular interaction field analysis of aminothiazole and thiazolesulfonamide as reversible LSD1 inhibitors

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Author(s):
Maltarollo, Vinicius G. [1] ; Honorio, Kathia M. [2, 3] ; Emery, Flavio S. [4] ; Ganesan, Arasu [5] ; Trossini, Gustavo H. G. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo - Brazil
[3] Fed Univ ABC, Ctr Nat & Human Sci, Sao Paulo - Brazil
[4] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, QHETEM, Sao Paulo - Brazil
[5] Univ E Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk - England
Total Affiliations: 5
Document type: Journal article
Source: Future Medicinal Chemistry; v. 7, n. 11, p. 1381-1394, 2015.
Web of Science Citations: 3
Abstract

Background: LSD-1 is an enzyme that removes methyl groups from lysine residues of histone proteins. LSD-1 inhibition decreases cellular proliferation and therefore represents a therapeutic target for cancer treatment. MAO and LSD-1 are both flavin adenine dinucleotide-dependent MAOs, and the MAO inhibitor, tranylcypromine, is currently undergoing clinical trials for cancer treatment because it acts as an irreversible LSD-1 inhibitor. Materials \& methods: The present study investigated new reversible LSD-1 inhibitors, in order to develop novel selective anticancer agents. We constructed 2 and 3D quantitative structure-activity relationship models by using a series of 54 aminothiazole and thiazolesulfonamide derivatives. Results: The models were validated internally and externally (q(2), 0.691 and 0.701; r(2), 0.894 and 0.937; r(test)(2), 0.785 and 0.644, for 2 and 3D models, respectively). Fragment contribution maps, as well as steric and electrostatic contour maps were generated in order to obtain chemical information related to LSD-1 inhibition. Conclusion: The thiazolesulfonamide group was fundamental to the inhibition of LSD-1 by these compounds and that bulky and aromatic substituents at the thiazole ring were important for their steric and electrostatic interactions with the active site of LSD-1. (AU)

FAPESP's process: 12/20990-2 - Antiinfective compounds: an evolution in the medicinal chemistry of leishmanicidal tiazoles and the search for new tuberculostic agents
Grantee:Flavio da Silva Emery
Support Opportunities: Regular Research Grants