Search results for "Medicinal chemistry"

From Ecology to Biotechnology, Study of the Defense Strategies of Algae and Halophytes (from Trapani Saltworks, NW Sicily) with a Focus on Antioxidan…

2019

This study aimed at the characterization of the antioxidant power of polyphenol extracts (PE) obtained from the algae Cystoseira foeniculacea (CYS) (Phaeophyta) and from the halophyte Halocnemum strobilaceum (HAL), growing in the solar saltworks of western Sicily (Italy), and at the evaluation of their anti-microfouling properties, in order to correlate these activities to defense strategies in extreme environmental conditions. The antioxidant properties were assessed in the PE based on the total antioxidant activity test and the reducing power test

Fishing anti-inflammatories from known drugs: In silico repurposing, design, synthesis and biological evaluation of bisacodyl analogues

2017

Herein is described in silico repositioning, design, synthesis, biological evaluation and structure-activity relationship (SAR) of an original class of anti-inflammatory agents based on a polyaromatic pharmacophore structurally related to bisacodyl (BSL) drug used in therapeutic as laxative. We describe the potential of TOMOCOMD-CARDD methods to find out new anti-inflammatory drug-like agents from a diverse series of compounds using the total and local atom based bilinear indices as molecular descriptors. The models obtained were validated by biological studies, identifying BSL as the first anti-inflammatory lead-like using in silico repurposing from commercially available drugs. Several bi…

2017

The side product of the cyclocondensation reaction between ethyl benzimidazole-2-carboxylate and the nitrile imine of the corresponding hydrazonyl chloride, C20H11BrClN5O, crystallized in two crystal forms. Form (1) is a co-crystal of the target compound (without any chlorine substituent) and a side product containing a Cl atom in position 2 of the bromophenyl group, C20H12BrN5O·0.143C20H11BrClN5O. (2) contains the pure side product. The slightly different conformation of the ring systems leads to a different packing of (1) and (2), but both crystal structures are dominated by π–π interactions.

Bacterial Biofilm Inhibition in the Development of Effective Anti-Virulence Strategy

2018

There is an urgent need for new therapeutic strategies to counteract the global threat of antibiotic resistance, which has become, in recent years, one of the major public health concern. An important contribution to the microbial survival in hostile environments has been given by the capability of pathogens to form sessile communities able to adhere to biotic or abiotic surfaces, known as biofilms.

On the Antibacterial Activity of Azacarboxylate Ligands: Lowered Metal Ion Affinities for Bis-amide Derivatives of EDTA do not mean Reduced Activity.

2018

EDTA is widely used as an inhibitor of bacterial growth, affecting the uptake and control of metal ions by microorganisms. We describe the synthesis and characterisation of two symmetrical bis-amide derivatives of EDTA, featuring glycyl or pyridyl substituents: AmGly2 and AmPy2 . Metal ion affinities (logK) have been evaluated for a range of metals (Mg2+ , Ca2+ , Fe3+ , Mn2+ , Zn2+ ), revealing less avid binding compared to EDTA. The solid-state structures of AmGly2 and of its Mg2+ complex have been determined crystallographically. The latter shows an unusual 7-coordinate, capped octahedral Mg2+ centre. The antibacterial activities of the two ligands and of EDTA have been evaluated against …

Quadruplex detection in human cells

2020

Abstract The precise detection of both DNA and RNA quadruplexes in human cells remains challenging. Efforts are being invested to design, synthesize and operate molecular tools to track and detect quadruplexes in cells. Such probes now have sufficient molecular specificity and suitable spectroscopic properties to shed light on quadruplexes in their cellular context, thus providing reliable details about their existence in cells. Herein, the most important steps in this line of development are summarized, from the very first attempts with organometallic complexes to the development of immunodetection technologies; and from in vitro to live-cell investigations performed with cell-permeable qu…

The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties.

2020

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here, we report its unique compact structure on the basis of four intramolecular thioether bridges introduced post-translationally by a specific radical-SAM sactisynthase. This structure con…

Lipoproteins LDL versus HDL as nanocarriers to target either cancer cells or macrophages

2020

free open access article 31 p.; International audience; In this work, we have explored natural unmodified low- and high-density lipoproteins (LDL and HDL) as selective delivery vectors in colorectal cancer therapy. We show in vitro in cultured cells and in vivo (NanoSPECT/CT) in the CT-26 mice colorectal cancer model that LDLs are mainly taken up by cancer cells, while HDLs are preferentially taken up by macrophages. We loaded LDLs with cisplatin and HDLs with the heat shock protein-70 inhibitor AC1LINNC, turning them into a pair of “Trojan horses” delivering drugs selectively to their target cells as demonstrated in vitro in human colorectal cancer cells and macrophages, and in vivo. Coupl…

Disclosing the actual efficiency of G-quadruplex-DNA–disrupting small molecules

2020

AbstractThe quest for small molecules that avidly bind to G-quadruplex-DNA (G4-DNA, or G4), so called G4-ligands, has invigorated the G4 research field from its very inception. Massive efforts have been invested to i- screen or design G4-ligands, ii- evaluate their G4-interacting properties in vitro through a series of now widely accepted and routinely implemented assays, and iii- use them as unique chemical biology tools to interrogate cellular networks that might involve G4s. In sharp contrast, only uncoordinated efforts at developing small molecules aimed at destabilizing G4s have been invested to date, even though it is now recognized that such molecular tools would have tremendous appl…

DNA folds threaten genetic stability and can be leveraged for chemotherapy

2020

International audience; Damaging DNA is a current and efficient strategy to fight against cancer cell proliferation. Numerous mechanisms exist to counteract DNA damage, collectively referred to as the DNA damage response (DDR) and which are commonly dysregulated in cancer cells. Precise knowledge of these mechanisms is necessary to optimise chemotherapeutic DNA targeting. New research on DDR has uncovered a series of promising therapeutic targets, proteins and nucleic acids, with application notably via an approach referred to as combination therapy or combinatorial synthetic lethality. In this review, we summarise the cornerstone discoveries which gave way to the DNA being considered as an…