Metal-binding cyclodextrins: Synthesis and complexation with Zn2+ and Ga3+ cations towards antimicrobial applications

carbohydrates,

The latest paper of our CSO, Milo Malanga resulted from a great collaboration with Marco Agnes, Gábor Benkovics, Georgios Miliotis, Dina Yannakopoulou, and several others, is just out!
We have prepared a family of cyclodextrins substituted with iminodiacetic acid (IDA) on their narrow side, while the wider side is either unmodified or per-2,3-O-methylated. The molecules form strong coordination complexes with Zn2+ or Ga3+ cations in aqueous solution. 50 μΜ of the compounds achieve complete re-sensitization of metallo-β-lactamase-producing Gram-negative clinical bacterial strains resistant to the carbapenems imipenem and meropenem.

Metal-binding cyclodextrins: Synthesis and complexation with Zn2+ and Ga3+ cations towards antimicrobial applications – ScienceDirect

Antibiotics in the clinical pipeline as of December 2022

drug discovery,

Do you think we are putting enough effort in developing novel antibiotics?
The need for new antibacterial drugs to treat the increasing global prevalence of drug-resistant bacterial infections has clearly attracted global attention, with a range of existing and upcoming funding, policy, and legislative initiatives designed to revive antibacterial R&D. Despite the promising early-stage antibacterial pipeline, it is essential to maintain funding for antibacterial R&D and to ensure that plans to address late-stage pipeline issues succeed.

See the full article here:

Antibiotics in the clinical pipeline as of December 2022 | The Journal of Antibiotics (nature.com)

The microbiome and human cancer

carbohydrates, ,

A review in Science Magazine by Greg Sepich-Poore, Ph.D. et al. looked at research that shows how bacteria, viruses and fungi of the microbiome are pervasive among human cancers, are key actors in cancer immunotherapy, and are potentially engineerable to treat metastases. Advances in microbiome research are improving our understanding of immuno-oncology and driving new diagnostic and therapeutic approaches.

Check out the article at the following link.


Carbohydrate derivatives fight against the malaria parasite as anti-plasmodial agents

carbohydrates,

Carbohydrate derivatives fight against the malaria parasite as anti-plasmodial agents.
In this review, the importance of carbohydrate derivatives of different classes of compounds as possible antimalarials with emphasis on mode of action, rational design, and SAR with improved efficacy are discussed. The new candidates with novel modes of action are potent antimalarial drug candidates without any parasitic resistance.

See the full article here!

Hydroxypropyl-β-Cyclodextrin Depletes Membrane Cholesterol and Inhibits SARS-CoV-2 Entry into HEK293T-ACEhi Cells

carbohydrates, , ,

Vaccination has drastically decreased mortality due to coronavirus disease 19 (covid19), but not the rate of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alternative strategies, such as inhibition of virus entry by interference with angiotensin-I-converting enzyme 2 (ACE2) receptors could be warranted. Cyclodextrins (CDs) are cyclic oligosaccharides that are able to deplete cholesterol from membrane lipid rafts, causing ACE2 receptors to relocate to areas devoid of lipid rafts. To explore the possibility of reducing SARS-CoV-2 entry, hydroxypropyl-β-cyclodextrin (HPβCD) was tested in a HEK293T-ACE2hi cell line stably overexpressing human ACE2 and Spike-pseudotyped SARS-CoV-2 lentiviral particles. Exposure of HEK293T-ACEhi cells to concentrations of HPβCD starting from 2.5 mM to 10 mM showed a concentration-dependent reduction of approximately 50% of the membrane cholesterol content. In addition, incubation of HEK293T-ACEhi cells with HIV-S-CoV-2 pseudotyped particles in the presence of increasing concentrations of HPβCD (from 0.1 to 10 mM) displayed a concentration-dependent effect on SARS-CoV-2 entry efficiency. These data indicate that HPβCD is a candidate for use as a SARS-CoV-2 prophylactic agent.

Silvia Alboni, Valentina Secco, Bianca Papotti, Antonietta Vilella, Maria Pia Adorni, Francesca Zimetti, Laurent Schaeffer, tascedda fabio, Michele Zoli, Pascal Leblanc, Erica Villa

See the full article here: Hydroxypropyl-β-Cyclodextrin Depletes Membrane Cholesterol and Inhibits SARS-CoV-2 Entry into HEK293T-ACEhi Cells

Veklury® (remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content

carbohydrates, drug delivery,

It has always been a bit of a mystery that given the antiviral effect of certain cyclodextrin, we can attribute all the antiviral effect of Veklury to remdesivir, which takes 3% of the formulation or maybe SBECD (97% of the formulation) also has some role. Researchers from University of Debrecen explore those questions.
Veklury® and different cholesterol-depleting cyclodextrins (CDs) reduced the binding of the spike receptor binding domain to ACE2 and spike trimer internalization for Wuhan-Hu-1, Delta, and Omicron variants. Correlations of these effects with cholesterol-dependent changes in membrane structure and decreased, lipid raft-dependent ACE2-TMPRSS2 interaction establish that SBECD is not simply a vehicle but also an effector in Veklury® due to its cholesterol-depleting potential.
Gyorgy Panyi, Florina Zakany et al.

See the full article here.

Synthesis of an amphiphilic vancomycin aglycone derivative inspired by polymyxins: overcoming glycopeptide resistance in Gram-positive and Gram-negative bacteria in synergy with teicoplanin in vitro

carbohydrates, ,

A fascinating journey in the world of novel glycopeptide antibiotics with stops such as overcoming resistance in Gram-positive and Gram-negative bacteria and combined antiviral and antibiotic effects guided by  Anikó Borbás and her group at University of Debrecen supported by several international KOLs in the field (Ilona Bakai-Bereczki, Ferenc Fenyvesi, Pal Herczegh, Eszter Ostorhazi, Henrietta Papp, Batta Gyula, Ana Mitrović, Janko Kos, István Hajdu, Dávid Bajusz, György Keseru, et al)

See the corresponding articles on nature.com:

Synthesis of an amphiphilic vancomycin aglycone derivative inspired by polymyxins: overcoming glycopeptide resistance in Gram-positive and Gram-negative bacteria in synergy with teicoplanin in vitro

Semisynthetic teicoplanin derivatives with dual antimicrobial activity against SARS-CoV-2 and multiresistant bacteria


Synthetic biomarkers for differential serological diagnosis of Cutaneous Leishmaniasis (CL) caused by various Leishmania species

carbohydrates, ,

Great patent on neoglycoconjugates and/or glycosides containing glycan selected from Galpα1,3Galfβ, Galpα1,6Galpα1,3Galfβ, or Galpα1,3Galfβ1,3Manpα and their use as diagnostic or prognostic biomarkers, vaccines, treating or detecting parasitic diseases, such as cutaneous leishmaniasis are disclosed.
The University of Texas at El Paso – Igor Almeida, Rosa Amelia Maldonado, Alvaro Acosta-Serrano, Susana Portillo et al.

See the full patent on Espacenet

Targeting bacterial virulence as a novel treatment against AMR infections

drug development, ,

Have you known that Arivin Therapeutics uses cyclodextrin for targeting bacterial virulence as a novel treatment against AMR infections? Among their MoA claims, the following are listed:
– Targeting virulence factors is effective, also against extensively resistant isolates
– Targeting virulence avoids rapid resistance
– Direct reduction in inflammatory responses
– Potentiates the function of antibiotics
Also, there is a spectacular video about how CDs develop their effect as antibacterials.

https://arivintx.com/our-science