Lipid reducing activity of novel cholic acid (CA) analogs: Design, synthesis and preliminary mechanism study

Luo, Guoshun; Qian, Zhouyang; Qiu, Rongmao; Qin, You

doi:10.1016/j.bioorg.2018.07.002

Cited by 3 publications

(7 citation statements)

References 48 publications

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“…In vitro , cholesterol efflux increased 379 , 381 and intracellular cholesterol as well as lipid content were reduced, 336 , 352 while plasma and liver triglycerides levels were reduced in vivo in high fat diet-fed C57BL/6 mice. 271 Interestingly, 14b induced farnesoid-X-receptor (FXR) transcription ( Fxr ), 336 and CL2-57 inhibited RXR-β, PPAR-γ, and PPAR-δ, 271 …”

Section: Part I: Status Quomentioning

confidence: 90%

“… 205 , 250 , 279 , 282 , 310 , 319 , 322 , 324 , 326 , 328 , 330 - 335 , 337 - 340 , 342 , 343 In addition, an induction of SREBP1C / Srebp1c has also been observed. 336 , 342 Functionally, TO901317 increased cholesterol efflux, 250 , 259 , 260 , 262 , 264 , 282 , 319 , 324 , 329 , 331 , 342 decreased intracellular Aβ content, and increased Aβ secretion from different murine brain cells. 126 , 345 Further, it reduced Aβ 25-35 -mediated toxicity toward cells by induction of Abca1 .…”

Section: Part I: Status Quomentioning

confidence: 98%

“… 271 , 336 , 352 , 379 - 382 The cholic acid analog 14b, 336 the thiophene derivative CL2-57, 271 as well as derivatives of N-benzothiazolyl-2-benzenesulfonamide, 379 ginsenoside, 352 and rutaecarpine, 367 all induced ABCA1 / Abca1 mRNA 336 , 352 , 381 and ABCA1 protein 271 , 336 , 379 , 381 content in vitro 271 , 336 , 379 and in vivo , 271 targeting the LXR-α/LXR-β pathway 352 by activation 271 or induction 336 of LXR-α/ LXRA / Lxra and/or LXR-β/ LXRB / Lxrb . In vitro , cholesterol efflux increased 379 , 381 and intracellular cholesterol as well as lipid content were reduced, 336 , 352 while plasma and liver triglycerides levels were reduced in vivo in high fat diet-fed C57BL/6 mice. 271 Interestingly, 14b induced farnesoid-X-receptor (FXR) transcription ( Fxr ), 336 and CL2-57 inhibited RXR-β, PPAR-γ, and PPAR-δ, 271 …”

Section: Part I: Status Quomentioning

confidence: 99%

“…Such synthetic approaches should be highlighted, 271 , 336 , 352 , 379 - 382 as chemical derivatization of ABCA1 inducers and elucidation of their structure-activity relationships (SAR) have not yet been comprehensively assessed. More reports are needed to gain innovative molecules that can be considered clinically for the treatment of various ABCA1-related diseases.…”

Section: Part I: Status Quomentioning

confidence: 99%

See 3 more Smart Citations

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Pahnke

Bascuñana

Brackhan

et al. 2021

Free Neuropathology

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Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer’s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited, and most of the 49 human ABC transporters have been largely neglected as potential targets for novel small-molecule drugs. This is especially true for the ABCA subfamily, which contains several members known to play a role in AD initiation and progression. This review provides up-to-date information on the proposed functional background and pathological role of ABCA transporters in AD. We also provide an overview of small-molecules shown to interact with ABCA transporters as well as potential in silico , in vitro , and in vivo methodologies to gain novel templates for the development of innovative ABC transporter-targeting diagnostics and therapeutics.

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Section: Part I: Status Quomentioning

confidence: 90%

Section: Part I: Status Quomentioning

confidence: 98%

Section: Part I: Status Quomentioning

confidence: 99%

Section: Part I: Status Quomentioning

confidence: 99%

See 2 more Smart Citations

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Pahnke

Bascuñana

Brackhan

et al. 2021

Free Neuropathology

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“…For instance, BA sulphonamides and cholic acid derivatives, containing amino acid or triazolyl fragments, show pronounced carbonic anhydrase inhibitory and anti-tuberculosis activities, respectively [16,17]. The particular attention of researchers in this field is also attracted to aminoalcohol moieties—it was shown that introduction of such fragments in BA molecules enhanced antifungal and lipid reducing activities [18,19] and improved gel-forming properties [20]. However, to the best of our knowledge, the anti-proliferative effects of aminoalcohol-containing BA derivatives have not been yet investigated.…”

Section: Introductionmentioning

confidence: 99%

Novel Derivatives of Deoxycholic Acid Bearing Linear Aliphatic Diamine and Aminoalcohol Moieties and their Cyclic Analogs at the C3 Position: Synthesis and Evaluation of Their In Vitro Antitumor Potential

et al. 2019

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A series of novel deoxycholic acid (DCA) derivatives containing aliphatic diamine and aminoalcohol or morpholine moieties at the C3 position were synthesized by 3,26-epoxide ring-opening reactions. These compounds were investigated for their cytotoxicity in four human tumor cell lines and murine macrophages and for inhibitory activity against macrophage-mediated NO synthesis in vitro. Obtained data revealed that: (i) all amine-containing substituents significantly increased the cytotoxicity of the novel compounds (IC502–10 = 1.0–36.0 μM) in comparison with DCA (IC50DCA ≥ 82.9 μM); (ii) aminoalcohol moieties were more preferable than diamine moieties due to the fact they imparted better selectivity for tumor cells of the novel derivatives; (iii) the susceptibility of tested cell lines to derivatives diminished in the following order: HuTu-80 (duodenal carcinoma) ≈ HepG2 (hepatocarcinoma) > KB-3-1 (cervical carcinoma) > RAW264.7 (macrophages) > A549 (lung carcinoma); (iv) compounds 8 and 9, bearing aminoethanol and aminopropanol moieties, respectively, exhibited high cytotoxic selectivity indexes (SIHuTu-80 = 7.9 and 8.3, respectively) and good drug-likeness parameters; (v) the novel compounds do not display anti-NO activity. Mechanistic study revealed that compound 9 induces ROS-dependent cell death by activation of intrinsic caspase-dependent apoptosis and cytodestructive autophagy in HuTu-80 cells and vitamin D receptor can be considered as its primary target.

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Aerobic Oxidation Reactions Using Metal-based Homogeneous Systems

Urgoitia

Herrero

SanMartı́n

2020

Catalytic Aerobic Oxidations

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Molecular oxygen is the reagent of choice for many organic reactions, including the oxidation of a variety of substrates. The importance of carbonyl and carboxylic compounds has boosted research on alternative approaches based on more sustainable reagents. To this end, aerobic oxidative approaches have emerged as a promising option to other entries involving Friedel-–Crafts acylation, Claisen condensation, esterification or amidation reactions. In comparison with the use of heterogeneous catalysts and organocatalysts, homogeneous catalysts provide considerably higher substrate : catalyst ratios and selectivities. This chapter summarizes the most remarkable reports on the use of homogeneous catalysts for the molecular oxygen-mediated oxidation of alcohols, active methylene compounds and oxidative cleavage of unsaturated hydrocarbons, with a focus on palladium, copper and ruthenium catalysts. Special attention will be paid to aspects such as catalyst amounts, the need for co-catalysts, the pressure of oxygen or air required and reaction media.

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Lipid reducing activity of novel cholic acid (CA) analogs: Design, synthesis and preliminary mechanism study

Cited by 3 publications

References 48 publications

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Novel Derivatives of Deoxycholic Acid Bearing Linear Aliphatic Diamine and Aminoalcohol Moieties and their Cyclic Analogs at the C3 Position: Synthesis and Evaluation of Their In Vitro Antitumor Potential

Aerobic Oxidation Reactions Using Metal-based Homogeneous Systems

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