An Investigation of Molecular Targeting of MMP-9 for Endometriosis Using Algal Bioactive Molecules

Sulfur-Fluoride Exchange (SuFEx) is the new generation click chemistry transformation exploiting the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx based protocol for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from the corresponding sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new protocol involves the rapid exchange of the S-F bond with trifluoromethyltrimethylsilane (TMSCF3) upon activation with potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative catalytic mechanism is proposed supported by DFT calculations, involving formation of the free trifluoromethyl anion followed by nucleophilic displacement of the S-F through a five-coordinate intermediate. The preparation of a benzothiazole derived bis(trifluoromethyl)sulfur oxyimine with cytotoxic selectivity for MCF7 breast cancer cells demonstrates the utility of this methodology for the late-stage functionalization of bioactive molecules.

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Reductive Cleavage of Secondary Sulfonamides: Converting Terminal Functional Groups into Versatile Synthetic Handles

10.26434/chemrxiv.9925145 ◽

2019 ◽

Author(s):

Patrick Fier ◽

Suhong Kim ◽

Kevin M. Maloney

Keyword(s):

Functional Groups ◽

Late Stage ◽

Reductive Cleavage ◽

Bioactive Molecules ◽

General Method

Sulfonamides are pervasive in drugs and agrochemicals, yet are typically considered as terminal functional groups rather than synthetic handles. To enable the general late-stage functionalization of secondary sulfonamides, we have developed a mild and general method to reductively cleave the N-S bonds of sulfonamides to generate sulfinates and amines, components which can further react in-situ to access a variety of other medicinally relevant functional groups. The utility of this platform is highlighted by the selective manipulation of several complex bioactive molecules.

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Faculty Opinions recommendation of Decreased affinity for efflux transporters increases brain penetrance and molecular targeting of a PI3K/mTOR inhibitor in a mouse model of glioblastoma.

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

10.3410/f.725496471.793507815 ◽

2015 ◽

Author(s):

Susan Bates

Keyword(s):

Mouse Model ◽

Mtor Inhibitor ◽

Molecular Targeting ◽

Efflux Transporters

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Faculty Opinions recommendation of The most common functional groups in bioactive molecules and how their popularity has evolved over time.

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

10.3410/f.738326294.793576699 ◽

2020 ◽

Author(s):

John Lowe

Keyword(s):

Functional Groups ◽

Bioactive Molecules ◽

Over Time

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Antibiotic-anionic Clay Matrix Used for Drug Controlled Release

Revista de Chimie ◽

10.37358/rc.18.2.6098 ◽

2018 ◽

Vol 69 (2) ◽

pp. 321-323

Author(s):

Georgeta Zegan ◽

Elena Mihaela Carausu ◽

Loredana Golovcencu ◽

Alina Sodor Botezatu ◽

Eduard Radu Cernei ◽

...

Keyword(s):

Controlled Release ◽

Layered Double Hydroxides ◽

Bioactive Molecules ◽

Drug Controlled Release ◽

Anionic Clays ◽

Anionic Clay ◽

Toxicological Studies ◽

High Efficient ◽

Clay Matrix ◽

Double Hydroxides

Anionic clay matrix acting as drug controlled release system have shown in last years a great potential for delivery of bioactive molecules and chemical therapeutics. This organic-inorganic nanohybrid system is high efficient offering an excellent protection of intercalated compounds from degradation. Compared to other nanoparticles used in medical area, anionic clays type layered double hydroxides have found to be biocompatible according to toxicological studies. Ampicillin containing MgAlLDHs and ZnAlLDH samples have been prepared following two routes: anion-exchange procedure and reconstruction from calcined layered double hydroxides. Solid samples have been characterized by FTIR and SEM-EDX highlighting the alteration of pristine LDHs structure when the antibiotic is introduced in the interlayer gallery.

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Role of Matrix Metalloproteinases in Degenerative Kidney Disorders

Current Medicinal Chemistry ◽

10.2174/0929867325666171205143441 ◽

2018 ◽

Vol 25 (15) ◽

pp. 1805-1816 ◽

Cited By ~ 6

Author(s):

Shifa Narula ◽

Chanderdeep Tandon ◽

Simran Tandon

Keyword(s):

Matrix Metalloproteinases ◽

Transforming Growth Factor ◽

Kidney Diseases ◽

Transforming Growth Factor Β1 ◽

Bioactive Molecules ◽

Tissue Inhibitors Of Metalloproteinases ◽

Ecm Remodeling ◽

Surface Receptors ◽

Calcium Dependent ◽

Ecm Degradation

Matrix metalloproteinases (MMPs) are members of calcium dependent-zinc containing endopeptidases that play a pivotal role in extracellular matrix (ECM) remodeling. MMPs are also known to cleave non-matrix proteins, including cell surface receptors, TNF-α, angiotensin-II, growth factors, (especially transforming growth factor-β1, ΤGF- β1) plasminogen, endothelin and other bioactive molecules. The tissue inhibitors of metalloproteinases (TIMPs) inhibit the activity of MMPs and decrease ECM degradation. Various patho-physiological conditions have been linked with the imbalance of ECM synthesis and degradation. Numerous studies have reported the significance of MMPs and TIMPs in the progression of kidney pathologies, including glomerulonephritis, diabetic nephropathy, renal cancer, and nephrolithiasis. Although dysregulated activity of MMPs could directly or indirectly lead to pathological morbidities, their contribution in disease progression is still understated. Specifically, MMP activity in the kidneys and it's relation to kidney diseases has been the subject of a limited number of investigations. Therefore, the aim of the present review is to provide an updated insight of the involvement of MMPs and TIMPs in the pathogenesis of inflammatory and degenerative kidney disorders.

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