Lipophilic phenolic antioxidants: Correlation between antioxidant profile, partition coefficients and redox properties

Roleira, Fernanda M.F.; Siquet, Christophe; Orrù, Elizabeta; Garrido, Eduardo; Garrido, Jorge; Milhazes, Nuno; Podda, Gianni; Paiva‐Martins, Fátima; Reis, Salette; Carvalho, Rui A.; Silva, E. J. Tavares da; Borges, Fernanda

doi:10.1016/j.bmc.2010.06.090

Cited by 101 publications

(90 citation statements)

References 43 publications

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“…Our SAR studies on a set of synthesized HCAs including caffeic acid, ferulic and related compounds have shown that derivatives with higher antioxidant efficacy (including caffeic acid and related compounds) have lower redox potential and those with lower antioxidant capacity (including ferulic acid and related derivatives) are associated with higher redox potentials [147]. We have also observed that methoxylation of ferulic acid leads to an increase in redox potential and a decrease in the antioxidant activity [82].…”

Section: [183] Cape and 5 Of Its Derivativesmentioning

confidence: 67%

“…Lipophilic antioxidants can penetrate cell membranes and may prevent oxidative damage to cells through membrane-related partitioning effects that supplement their chemical activities [121]. Compounds possessing sufficient lipophilic character would also be able to cross the blood-brain barrier (BBB) and hence act as potential radical scavenging agents for protection against oxidative stress in the central nervous system [147]. On the other hand, inefficiency of dietary HCAs in relieving neuronal oxidative stress has been related mainly to their inability to pass through BBB [149].…”

Section: Lipid Solubilitymentioning

confidence: 99%

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Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships

Razzaghi‐Asl¹,

Garrido²,

Khazraei³

et al. 2013

CMC

172

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Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxi-dant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the car-boxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activ-ity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimiza-tion of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be use-ful for management of oxidative stress-related diseases.Keywords: Antioxidant, hydroxycinnamic acids, in vitro, ROS, structure-activity relationships. OXIDATIVE STRESS AND ANTIOXIDANTSReactive oxygen species (ROS) are oxygen derived molecules that readily react with other compounds and macromolecules and oxidize them. Some representative exam-ples of these species include superoxide (O2•-), hydroxy (HO • ) and peroxy (ROO • ) radicals, hydrogen peroxide (H2O2) and singletROS are involved in important physiological processes such as immune response, gene expression, signal transduc-tion and growth regulation [5,6]; however if they are not kept under tight control by physiological antioxidant systems they will be able to oxidize and damage various biological molecules leading to a condition called oxidative stress [1,7,8]. In this regard, oxidative stress has been reported to be in-volved in the pathogenesis of diseases such as cancer [9], neurodegenerative diseases [10], stroke [11], and others [12,13].Since an important source of ROS comes from environment [14], with the industrial development and the change in life style, oxidative stress related diseases need a special attention [15].Antioxidants operate by preventing or slowing the progression of oxidative damage reactions [16,17]. An antioxidant has been defined as "any substance that delays, p...

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Section: [183] Cape and 5 Of Its Derivativesmentioning

confidence: 67%

Section: Lipid Solubilitymentioning

confidence: 99%

Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships

Razzaghi‐Asl¹,

Garrido²,

Khazraei³

et al. 2013

CMC

172

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“…Especially, p-coumaric acid or 4-hydroxy-trans-cinnamic acid presents antioxidant activity, involving direct scavenger of reactive oxygen species (ROS) by minimizing the oxidation of low-density lipoprotein (LDL) [16]. Lipophilic hexylamides and hexylesters of cinnamic and hydrocinnamic acids as well as the corresponding acid precursors, have been recently studied for their antioxidant profile and found to play important role in neurodegenerative diseases (ND) due to their ability to cross the blood-brain barrier [17]. Additionally, 2'-hydroxycinnamaldehyde and the analogue 2'-benzoyloxycinnamaldehyde induce apoptosis in cancer cells via the induction of cellular reactive oxygen species (ROS) [18].…”

Section: Introductionmentioning

confidence: 99%

Novel Cinnamic Acid Derivatives as Antioxidant and Anticancer Agents: Design, Synthesis and Modeling Studies

et al. 2014

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Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX inhibitor. Phenylsubstituted acids showed better inhibitory activity against soybean LOX, and it must be noted that compounds 4i and 3i with higher lipophilicity values resulted less active than compounds 2i and 1i. The compounds have shown very good activity in different antioxidant assays. The antitumor properties of these derivatives have been assessed by their 1/IC 50 inhibitory values in the proliferation of HT-29, A-549, OAW-42, MDA-MB-231, HeLa and MRC-5 normal cell lines. The compounds presented low antitumor activity considering the IC 50 values attained for the cell lines, with the exception of compound 4ii. Molecular docking studies were carried out on cinnamic acid derivative 4ii and were found to be in accordance with our experimental biological results.

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“…The amides 3, 4 and 5 (Scheme 1) were obtained in 69%, 54% and 35% yield, respectively, by reacting acid 1 with tert-butylamine, npropylamine or n-hexylamine, in dimethylformamide and dichloromethane, using triethylamine and the coupling agent BOP [28] probably through the intermediate 7. In spite of amide 3 has already been prepared in 89% [20] and in 95% [29] using thionyl chloride followed by tert-butylamine, in this work we present a one-step reaction using milder conditions.…”

Section: Chemistrymentioning

confidence: 99%

New steroidal 17β-carboxy derivatives present anti-5α-reductase activity and anti-proliferative effects in a human androgen-responsive prostate cancer cell line

et al. 2013

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a b s t r a c tThe androgens testosterone (T) and dihydrotestosterone (DHT), besides playing an important role in prostate development and growth, are also responsible for the development and progression of benign prostate hyperplasia (BPH) and prostate cancer. Therefore, the actions of these hormones can be antagonized by preventing the irreversible conversion of T into DHT by inhibiting 5a-reductase (5a-R). This has been a useful therapeutic approach for the referred diseases and can be achieved by using 5a-reductase inhibitors (RIs). Steroidal RIs, finasteride and dutasteride, are used in clinic for BPH treatment and were also proposed for chemoprevention of prostate cancer. Nevertheless, due to the increase in bone and muscle loss, impotency and occurrence of high-grade prostate tumours, it is important to seek for other potent and specific molecules with lower side effects. In the present work, we designed and synthesized steroids with the 3-keto-D 4 moiety in the A-ring, as in the 5a-R substrate T, and with carboxamide, carboxyester or carboxylic acid functions at the C-17b position. The inhibitory 5a-R activity, in human prostate microsomes, as well as the anti-proliferative effects of the most potent compounds, in a human androgen-responsive prostate cancer cell line (LNCaP cells), were investigated. Our results showed that steroids 3, 4 and 5 are good RIs, which suggest that C-17b lipophylic amides favour 5a-R inhibition. Moreover, these steroids induce a decrease in cell viability of stimulated LNCaP cells, in a 5a-R dependent-manner, similarly to finasteride.

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Lipophilic phenolic antioxidants: Correlation between antioxidant profile, partition coefficients and redox properties

Cited by 101 publications

References 43 publications

Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships

Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships

Novel Cinnamic Acid Derivatives as Antioxidant and Anticancer Agents: Design, Synthesis and Modeling Studies

New steroidal 17β-carboxy derivatives present anti-5α-reductase activity and anti-proliferative effects in a human androgen-responsive prostate cancer cell line

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