G-quadruplexes are special secondary structures adopted in some guanine-rich DNA sequences. As guanine-rich sequences are present in important regions of the eukaryotic genome, such as telomeres and the regulatory regions of many genes, such structures may play important roles in the regulation of biological events in the body. G-quadruplexes have become valid targets for new anticancer drugs in the past few decades. Many leading compounds that target these structures have been reported, and a few of them have entered preclinical or clinical trials. Nonetheless, the selectivity of this kind of antitumor compound has yet to be improved in order to suppress the side effects caused by nonselective binding. As drug design targets, the topology and structural characteristics of quadruplexes, their possible biological roles, and the modes and sites of small-ligand binding to these structures should be understood clearly. Herein we provide a summary of published research that has set out to address the above problem to provide useful information on the design of small ligands that target G-quadruplexes. This review also covers research methodologies that have been developed to study the binding of ligands to G-quadruplexes.

A series of 5-N-methyl quindoline (cryptolepine) derivatives (2a- x) as telomeric quadruplex ligands was synthesized and evaluated. The designed ligands possess a positive charge at the 5- N position of the aromatic quindoline scaffold. The quadruplex binding of these compounds was evaluated by circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, nuclear magnetic resonance (NMR), and molecular modeling studies. Introduction of a positive charge not only significantly improved the binding ability but also induced the selectivity toward antiparallel quadruplex, whereas the nonmethylated derivatives tended to stabilize hybrid-type quadruplexes. NMR and molecular modeling studies revealed that the ligands stacked on the external G-quartets and the positively charged 5- N atom could contribute to the stabilizing ability. Long-term exposure of human cancer cells to 2r showed a remarkable cessation in population growth and cellular senescence phenotype and accompanied by a shortening of the telomere length.

Four isaindigotone derivatives (5a,b and 6a,b) designed as telomeric G-quadruplex ligands have been synthesized and characterized. The unfused aromatic rings in these compounds allow a flexible and adaptive conformation in G-quadruplex recognition. The interaction of human telomeric G-quadruplex DNA with these designed ligands was explored by means of FRET melting, fluorescence titration, CD spectroscopy, continuous variation, and molecular modeling studies. Our results showed that the adaptive scaffold might not only allow the ligands to well occupy the G-quartet but also perfectly bind to the grooves of the G-quadruplex. The synergetic effect of the multiple binding modes might be responsible for the improved binding ability and high selectivity of these ligands toward G-quadruplex over duplex DNA. Long-term exposure of HL60 and CA46 cancer cells to compound 5a showed a remarkable decrease in population growth, cellular senescence phenotype, and shortening of the telomere length, which is consistent with the behavior of an effective telomeric G-quadruplex ligand and telomerase inhibitor.

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Key aroma compounds in Chinese popular fried food of youtiao were characterized by solvent assisted flavor evaporation combined with gas chromatography‐mass spectrometry (GC‐MS) and aroma extract dilution analysis of gas chromatography‐olfactometry (AEDA/GC‐O), quantitation, and aroma recombination and omission. Four samples of youtiao fried with sunflower oil, soybean oil, rapeseed oil, and palm oil, respectively, differing in fatty acid composition, were selected to be investigated. A total of thirty‐five odorants were identified, among which twenty‐two odorants were quantitated by aid of authentic chemicals and with correction of recovery coefficients. Differences in odorants composition and aroma profile were observed among the four samples of youtiao fried with different oils. However, it was demonstrated in common thirteen compounds; that is, 3‐hydroxy‐2‐butanone, 3‐methylbutanal, furfural, 3‐(methylthio)propanal, 2‐furfurylthiol, phenylacetaldehyde, 2,5‐dimethyl‐4‐hydroxy‐3(2H)‐furanone, 2‐ethyl‐3,5‐dimethylpyrazine, 3‐ethyl‐2,5‐dimethylpyrazine, (E,E)‐2,4‐decadienal, 1‐octen‐3‐ol, (E,Z)‐2,6‐nonadienal, and (E)‐2‐nonenal contributed significantly to youtiao aroma. The work can provide some guidance to maintain the preferred youtiao flavor when modifying its preparation technology for safety concerns.

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