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Fluorescence resonance energy transfer melting assays showed that IQcs with a positive charge in the heteroaromatic nucleus and two weakly basic side chains are potent and selective human telomeric (HT) and gene promoter G4 stabilizers. Spectroscopic studies with HT G4 as a model showed that an IQc stabilizing complex involves the binding of two IQc molecules (2,9\u2010bis{[3\u2010(diethylamino)propyl]amino}\u20105\u2010methyl\u201011<jats:italic>H<\/jats:italic>\u2010indolo[3,2\u2010<jats:italic>c<\/jats:italic>]quinolin\u20105\u2010ium chloride, <jats:bold>3\u2009d<\/jats:bold>) per G4 unit, in two non\u2010independent but equivalent binding sites. Molecular dynamics studies suggest that end\u2010stacking of <jats:bold>3\u2009d<\/jats:bold> induces a conformational rearrangement in the G4 structure, driving the binding of a second <jats:bold>3\u2009d<\/jats:bold> ligand to a G4 groove. Modeling studies also suggest that <jats:bold>3\u2009d<\/jats:bold>, with two three\u2010carbon side chains, has the appropriate geometry to participate in direct or water\u2010mediated hydrogen bonding to the phosphate backbone and\/or G4 loops, assisted by the terminal nitrogen atoms of the side chains. Additionally, antiproliferative studies showed that IQc compounds <jats:bold>2\u2009d<\/jats:bold> (2\u2010{[3\u2010(diethylamino)propyl]amino}\u20105\u2010methyl\u201011<jats:italic>H<\/jats:italic>\u2010indolo[3,2\u2010<jats:italic>c<\/jats:italic>]quinolin\u20105\u2010ium chloride) and <jats:bold>3\u2009d<\/jats:bold> are 7\u2010 to 12\u2010fold more selective for human malignant cell lines than for nonmalignant fibroblasts.<\/jats:p>","DOI":"10.1002\/cmdc.201500067","type":"journal-article","created":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T08:49:55Z","timestamp":1427446195000},"page":"836-849","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Indolo[3,2\u2010<i>c<\/i>]quinoline G\u2010Quadruplex Stabilizers: a Structural Analysis of Binding to the Human Telomeric G\u2010Quadruplex"],"prefix":"10.1002","volume":"10","author":[{"given":"Jo\u00e3o","family":"Lavrado","sequence":"first","affiliation":[]},{"given":"Stephan A.","family":"Ohnmacht","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Correia","sequence":"additional","affiliation":[]},{"given":"Clara","family":"Leit\u00e3o","sequence":"additional","affiliation":[]},{"given":"S\u00edlvia","family":"Pisco","sequence":"additional","affiliation":[]},{"given":"Mekala","family":"Gunaratnam","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Moreira","sequence":"additional","affiliation":[]},{"given":"Stephen","family":"Neidle","sequence":"additional","affiliation":[]},{"given":"Daniel J. 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