Dicaffeoyltartaric Acid and Dicaffeoylquinic Acid HIV Integrase Inhibitors

Crosby, David C.; Robinson, William E.

doi:10.1002/9781118015377.ch23

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…The first drug using integrase inhibitor (Raltegravir) was approved by the US Food and Drug Administration (FDA) in 2007 while still others are being actively tested in clinical trials [10]. The focus on integrase inhibitors, especially L-chicoric acid for developing successful anti-HIV drug therapy, has been a promising area of study [3,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Organic Crop Management Enhances Chicoric Acid Content in Lettuce

Rajashekar

Oh²,

Carey³

2012

FNS

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L- chicoric acid is a dominant phenolic compound in lettuce (Lactuca sativa L.) and has been shown to accumulate in response to many abiotic stresses and crop management practices. It is a potent inhibitor of human immunodeficiency virus (HIV-1) integrase needed for the replication of this virus and for the productive infection of the host cell. L- chicoric acid has been found to act synergistically in combination with anti-HIV drugs used for treating acquired immuno-deficiency disorder (AIDS). We show in this study that organic management practices increase the chicoric acid content by nearly 2-fold compared to conventional management practices while they did not have a significant effect on the overall accumulation of phenolic compounds and antioxidants. Similar increase was observed in quercetin-3-O-glucoside under organic management. In addition, pre-plant fertilization decreased the levels of many phenolic compounds including chicoric acid under organic management unlike under conventional management. However, organically managed crop without pre-plant fertilization had better growth and produced about 2.5 times higher yield and higher chicoric acid content than did the conventionally managed crop. Thus, the results show that long term organic crop management practices, but avoiding pre-plant fertilization, can significantly enhance the yield of antiretroviral agent chicoric acid in lettuce

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Section: Introductionmentioning

confidence: 99%

Organic Crop Management Enhances Chicoric Acid Content in Lettuce

Rajashekar

Oh²,

Carey³

2012

FNS

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Mutagenesis of Lysines 156 and 159 in Human Immunodeficiency Virus Type 1 Integrase (IN) Reveals Differential Interactions between these Residues and Different IN Inhibitors

Crosby

Lei

Gibbs

et al. 2015

Natural Product Communications

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Human immunodeficiency virus (HIV) type 1 integrase (IN) active site, and viral DNA-binding residues K156 and K159 are predicted to interact both with strand transfer-selective IN inhibitors (STI), e.g. L-731,988, Elvitegravir (EVG), and the FDA-approved IN inhibitor, Raltegravir (RGV), and strand transfer non-selective inhibitors, e.g. dicaffeoyltartaric acids (DCTAs), e.g. L-chicoric acid (L-CA). To test posited roles for these two lysine residues in inhibitor action we assayed the potency of L-CA and several STI against a panel of K156 and K159 mutants. Mutagenesis of K156 conferred resistance to L-CA and mutagenesis of either K156 or K159 conferred resistance to STI indicating that the cationic charge at these two viral DNA-binding residues is important for inhibitor potency. IN K156N, a reported polymorphism associated with resistance to RGV, conferred resistance to L-CA and STI as well. To investigate the apparent preference L-CA exhibits for interactions with K156, we assayed the potency of several hybrid inhibitors containing combinations of DCTA and STI pharmacophores against recombinant IN K156A or K159A. Although K156A conferred resistance to diketo acid-branched bis-catechol hybrid inhibitors, neither K156A nor K159A conferred resistance to their monocatechol counterparts, suggesting that bis-catechol moieties direct DCTAs toward K156. In contrast, STI were more promiscuous in their interaction with K156 and K159. Taken together, the results of this study indicate that DCTAs interact with IN in a manner different than that of STI and suggest that DCTAs are an attractive candidate chemotype for development into drugs potent against STI-resistant IN.

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Dicaffeoyltartaric Acid and Dicaffeoylquinic Acid HIV Integrase Inhibitors

Cited by 2 publications

References 35 publications

Organic Crop Management Enhances Chicoric Acid Content in Lettuce

Organic Crop Management Enhances Chicoric Acid Content in Lettuce

Mutagenesis of Lysines 156 and 159 in Human Immunodeficiency Virus Type 1 Integrase (IN) Reveals Differential Interactions between these Residues and Different IN Inhibitors

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