A common mechanism links activities of butyrate in the colon

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation) demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup> in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.

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Enriching the Arsenal of Pharmacological Tools against MICAL2

Molecules ◽

10.3390/molecules26247519 ◽

2021 ◽

Vol 26 (24) ◽

pp. 7519

Author(s):

Ivana Barravecchia ◽

Elisabetta Barresi ◽

Camilla Russo ◽

Francesca Scebba ◽

Chiara De Cesari ◽

...

Keyword(s):

Human Cancer ◽

Biological Activities ◽

Microvascular Endothelial Cells ◽

The Novel ◽

Invasive Front ◽

Structure Activity ◽

Molecule Inhibitor ◽

Cancer Types ◽

Cytoskeleton Dynamics ◽

New Compounds

Molecule interacting with CasL 2 (MICAL2), a cytoskeleton dynamics regulator, are strongly expressed in several human cancer types, especially at the invasive front, in metastasizing cancer cells and in the neo-angiogenic vasculature. Although a plethora of data exist and stress a growing relevance of MICAL2 to human cancer, it is worth noting that only one small-molecule inhibitor, named CCG-1423 (1), is known to date. Herein, with the aim to develop novel MICAL2 inhibitors, starting from CCG-1423 (1), a small library of new compounds was synthetized and biologically evaluated on human dermal microvascular endothelial cells (HMEC-1) and on renal cell adenocarcinoma (786-O) cells. Among the novel compounds, 10 and 7 gave interesting results in terms of reduction in cell proliferation and/or motility, whereas no effects were observed in MICAL2-knocked down cells. Aside from the interesting biological activities, this work provides the first structure–activity relationships (SARs) of CCG-1423 (1), thus providing precious information for the discovery of new MICAL2 inhibitors.

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Advances in studies on histone deactylase inhibitors as anticancer drugs

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0012.7749 ◽

2018 ◽

Vol 72 ◽

pp. 1018-1031 ◽

Cited By ~ 1

Author(s):

Katarzyna Lipska ◽

Agata A. Filip ◽

Anna Gumieniczek

Keyword(s):

Anticancer Drugs ◽

Histone Deacetylases ◽

Cyclic Peptides ◽

Chemical Structure ◽

Chromatin Condensation ◽

Short Chain Fatty Acids ◽

Structure Activity ◽

The Usa ◽

Therapeutic Properties ◽

Naphthol Derivatives

Inhibitors of histone deacetylases (HDIs), by affecting the process of histone acetylation, lead to changes in chromatin condensation, and in consequence, to changes in the expression of numerous genes responsible for the cell cycle and differentiation. Therefore, they can be effective in the treatment of cancer. The antitumor activity for over 15 HDIs has been confirmed so far, and some of them have been approved in the USA and Europe, mainly in combination with cytostatics or radiotherapy. For several HDIs, large clinical trials are being carried out to estimate their effectiveness, in monotherapy and new combinations. Other synthetic and natural compounds with HDI activity are tested in preclinical studies. HDIs differ in terms of chemical structure, biological activity and specificity in relation to individual HDACs. The compounds active against classic HDACs (Zn2+-dependent metalloproteins) are usually characterized by the presence the Zn2+ binding group, the linker part and the capping group. Taking into account the type of Zn2+ binding group, classic HDIs are classified as short-chain fatty acids, hydroxamic acids, cyclic peptides and benzamides. In turn, the nicotinamide adenine dinucleotide-dependent SIRTs inhibitors are small molecules, mostly nicotinamide and β-naphthol derivatives. The presented paper summarizes the most important information regarding the use of HDIs as anticancer drugs, regarding their diversified chemical structure, activity against HDACs, additional therapeutic properties and side effects. The review was made taking into account the literature from the last five years (2013-2017).

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Derivatives and Analogues of Resveratrol: Recent Advances in Structural Modification

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190128093840 ◽

2019 ◽

Vol 19 (10) ◽

pp. 809-825 ◽

Cited By ~ 6

Author(s):

Qing-Shan Li ◽

Yao Li ◽

Girdhar Singh Deora ◽

Ban-Feng Ruan

Keyword(s):

Structural Modification ◽

Biological Activities ◽

Biological Properties ◽

Synthetic Analogues ◽

Pharmacological Activities ◽

The Past ◽

Structure Activity ◽

Clinical Drugs ◽

New Compounds ◽

Reliable Basis

Resveratrol is a non-flavonoid polyphenol containing a terpenoid backbone. It has been intensively studied because of its various promising biological properties, such as anticancer, antioxidant, antibacterial, neuroprotective and anti-inflammatory activities. However, the medicinal application of resveratrol is constrained by its poor bioavailability and stability. In the past decade, more attention has been focused on making resveratrol derivatives to improve its pharmacological activities and pharmacokinetics. This review covers the literature published over the past 15 years on synthetic analogues of resveratrol. The emphasis is on the chemistry of new compounds and relevant biological activities along with structure-activity relationship. This review aims to provide a scientific and reliable basis for the development of resveratrol-based clinical drugs.

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A comparative analysis of cultivation techniques of epithelial stem cells of cornea and creation of biomedical cell product (biocomposite) on the basis biocompatible matrix and stem cells

Genes and Cells ◽

10.23868/201912029 ◽

2019 ◽

Vol XIV (4) ◽

Author(s):

Z. Kvacheva ◽

I. Vasilevich ◽

A. Chekina ◽

L. Marchenko ◽

M. Dzhumova ◽

...

Keyword(s):

Stem Cells ◽

Comparative Analysis ◽

Epithelial Stem Cells ◽

Cell Product ◽

Cultivation Techniques

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Faculty Opinions recommendation of Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732001680.793540994 ◽

2017 ◽

Author(s):

Suzanne Watt

Keyword(s):

Stem Cells ◽

Tissue Damage ◽

Epithelial Stem Cells

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Characterization of Human Mammary Epithelial Stem Cells

10.21236/ada501896 ◽

2008 ◽

Author(s):

Peter D. Eirew

Keyword(s):

Stem Cells ◽

Mammary Epithelial ◽

Epithelial Stem Cells ◽

Human Mammary Epithelial

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Characterization of Human Mammary Epithelial Stem Cells

10.21236/ada516902 ◽

2007 ◽

Author(s):

Peter D. Eirew

Keyword(s):

Stem Cells ◽

Mammary Epithelial ◽

Epithelial Stem Cells ◽

Human Mammary Epithelial

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Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics

Current Medicinal Chemistry ◽

10.2174/0929867324666171009122612 ◽

2018 ◽

Vol 25 (5) ◽

pp. 636-658 ◽

Cited By ~ 22

Author(s):

Jan Pokorny ◽

Lucie Borkova ◽

Milan Urban

Keyword(s):

Biological Activities ◽

Synthetic Approach ◽

Clinical Use ◽

New Approach ◽

Click Reactions ◽

Drug Candidates ◽

The Past ◽

Low Toxicity ◽

New Compounds ◽

Potential Therapeutics

Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates.

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