Abiotic Main Group Pharmacophore Renders a New Class of Antimicrobial Agents

Wang, Yueying; Spokoyny, Alexander M.

doi:10.1021/acscentsci.2c00187

Cited by 7 publications

(10 citation statements)

References 9 publications

(28 reference statements)

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“…properties of all synthetized compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and parent unmodified clusters (1 and 2). Among the tested compounds, we identified several metallacarborane derivatives with good activity against S. aureus, while none showed activity against P. aeruginosa.…”

Section: Table 1 Contains Results Obtained From Initial Screening Of ...mentioning

confidence: 99%

“…A promising source of new pharmacophores for antimicrobial therapy are boron clusters. 2,3 Courtesy of boron self-catenation, boron clusters constitute a large family of abiotic, polyhedral boron hydrides and their heteroatom derivatives. [4][5][6] This structural diversity can be further combined with the ease of modification of boron clusters with organic substituents, resulting in an almost infinite number of derivatives.…”

Section: Introductionmentioning

confidence: 99%

“…3 cells/well density for the A-549 and UM-UC-3 cell lines and 2×103 cells/well for the MCF-10A and Balb/3T3 cell lines. After overnight incubation, compounds were applied at various concentrations (ranging from 50 µM to 0.01 nM).…”

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confidence: 99%

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Structural patterns enhancing the antibacterial activity of metallacarborane-based antibiotics

Cebula

Fink

Goldeman

et al. 2023

Preprint

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Each year, the number of infections caused by multidrug-resistant bacteria is increasing, making new public health crises likely in the future. To prevent this, novel drugs capable of overcoming current resistances are needed. Boron cluster-based antibiotics offer a valuable possibility to create a new class of antibiotics and expand antibiotic's chemical space beyond conventional carbon-based molecules. In this work, we identified the two most promising structural patterns providing cobalta bis(dicabrollide)(COSAN)-based compounds with potent and selective activity toward Staphylococcus aureus (including clinical strains): introduction of the -amino acid amide to the molecule and the addition of iodine directly to the metallacarborane cage. Furthermore, we found that proper hydrophobic-hydrophilic balance is crucial for the selective activity of the tested compounds toward S. aureus over mammalian cells. The patterns proposed in this paper can be useful in the development of metallacarborane-based antibiotics with potent antibacterial properties and low cytotoxicity.

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Section: Table 1 Contains Results Obtained From Initial Screening Of ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural patterns enhancing the antibacterial activity of metallacarborane-based antibiotics

Cebula

Fink

Goldeman

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…3 cells/well density for the A-549 and UM-UC-3 cell lines and 2×103 cells/well for the MCF-10A and Balb/3T3 cell lines.…”

mentioning

confidence: 99%

Structural patterns enhancing the antibacterial activity of metallacarborane-based antibiotics

Cebula

Fink

Goldeman

et al. 2022

Preprint

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Newly developed antibiotics are supposed to treat infections caused by drug-resistant bacteria. To increase the likelihood of overcoming resistance, antibiotic candidates should be based on structures that are unknown to bacteria. This is why boron-based antibiotics offer an interesting alternative to carbon-based drugs. This work is devoted to the development of a new group of antibiotics based on abiotic metallacarborane, cobalta bis(dicabrollide) (COSAN). We managed to identify the two most promising structural patterns that cause COSAN-based compounds to be selectively active toward S. aureus: the introduction of α-amino acid amide in the organic part of the molecule and the addition of iodine directly to the metallacarborane cage. The first modification provided selective activity of the tested compounds toward S. aureus over mammalian cells through proper hydrophobic-hydrophilic balance. The second modification increased all observed biological activities. The patterns proposed in this paper can be used in the development of metallacarborane-based antibiotics that have potent antibacterial properties and low cytotoxicity.

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Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport

Salluce,

Folgar‐Cameán,

Barba‐Bon

et al. 2024

Angewandte Chemie

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Perhalogenated closo‐borates represent a new class of membrane carriers. They owe this activity to their chaotropicity, which enables the transport of hydrophilic molecules across model membranes and into living cells. The transport efficiency of this new class of cluster carriers depends on a careful balance between their affinity to membranes and cargo, which varies with chaotropicity. However, the structure‐activity parameters that define chaotropic transport remain to be elucidated. Here, we have studied the modulation of chaotropic transport by decoupling the halogen composition from the boron core size. The binding affinity between perhalogenated decaborate and dodecaborate clusters carriers was quantified with different hydrophilic model cargos, namely a neutral and a cationic peptide, phalloidin and (KLAKLAK)2. The transport efficiency, membrane‐lytic properties, and cellular toxicity, as obtained from different vesicle and cell assays, increased with the size and polarizability of the clusters. These results validate the chaotropic effect as the driving force behind the membrane transport propensity of boron clusters. This work advances our understanding of the structural features of boron cluster carriers and establishes the first set of rational design principles for chaotropic membrane transporters.

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Abiotic Main Group Pharmacophore Renders a New Class of Antimicrobial Agents

Abstract: A boron cluster is used to template a hybrid molecular scaffold capable of killing multiple pathogenic and antibiotic-resistant bacterial strains.

Cited by 7 publications

References 9 publications

Structural patterns enhancing the antibacterial activity of metallacarborane-based antibiotics

Structural patterns enhancing the antibacterial activity of metallacarborane-based antibiotics

Structural patterns enhancing the antibacterial activity of metallacarborane-based antibiotics

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport

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