Infections caused by Candida species have increased significantly in the past decades and are among the leading causes of morbidity and mortality worldwide, resulting in serious public health problems. Currently, conventional antifungals are often ineffective as Candida spp. have developed growing resistance to systemic drugs. Since inorganic metallacarboranes are known to affect cellular events, new derivatives of these abiotic compounds were tested against Candida albicans. Compounds based on cobalt bis-dicarbollide [COSAN] were studied on Candida albicans strains, including a panel of 100 clinical isolates. The presented data prove that metallacarborane derivatives are effective against clinical isolates of Candida albicans, even those resistant to systemic drugs, and show synergistic potential in combination with amphotericin B, and low toxicity against human cells and Danio rerio embryos. This paper is a consequential step in the investigations of the broad spectrum and valuable future medical applications of metallacarboranes, especially in the fight against drug-resistant pathogens.

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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.