Abstract Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 μg/mL and MFC 62.5 μg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 μg/mL), and C. tropicalis (MIC 31.2 μg/mL and MFC 125 μg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained.

The emergence of antibiotic resistance among microbial pathogens is a serious public health problem, resulting in a constant need of discovering new antibiotics. For this purpose, we synthetized and determined the antimicrobial activity of copper (Cu), cobalt (Co), and tin (Sn) complexes coordinated with scorpionate ligand in a tridentate mode against microorganisms of clinical importance. New complexes with the sodium hydrotris(2-mercaptothiazolyl)borate ligand were characterized by physicochemical and spectroscopic techniques (UV-vis, IR, 1H and 13C NMR). Moreover, their antimicrobial activity was evaluated using microdilution broth method. Cytotoxicity was determined in Vero cells and the selectivity index (SI) was calculated. The coordination with metals increased the ligand antimicrobial activity, which showed no activity when evaluated alone (MIC>1,080 µM). Cu-complex (1) had activity against Candida albicans and C. krusei, with MICs of 130 and 66 µM, respectively. The compounds had low toxicity on Vero cells and chemo-informatics assays corroborated a low systemic toxic effect. The SI revealed that the compound 1 was 16 times more selective for C. krusei and 8 times more selective for C. albicans in relation to Vero cells. The Cu-complex stands out as a potential prototype for the development of new antifungal agents.

Abstract: Four novel Cr (III), Co (II) and Ni (II) complexes with 2-thiazoline-2-tiol derivative ligands were synthesized and characterized using elemental, physiochemical, and spectroscopy analytical methods. The results showed the formation of ligands coordinated by sulfur atoms of the C = S bond to the L1 ligand and by the sulfur atom of the C-S bond and/or nitrogen of the intra C-ring bond of the L2 ligand. The activity of the complexes against Gram-negative, Gram-positive bacteria and yeasts of clinical importance was evaluated by broth microdilution method. The best result was obtained to L2-Ni compound against E. cloacae (Minimal Inhibitory Concentration (MIC) = 62.5 µg/mL). Additionally, the compounds showed anti-Candida activity (MIC values ranging from 250 to 500 µg/mL), except the L1-Cr that was not active against any tested microorganism.

ABSTRACT The antibacterial activity of plant extracts of the Lamiaceae family was evaluated against clinical isolates of multi-resistant Gram-negative bacteria by broth microdilution technique. Promising results were obtained considering that all extracts were active for at least two bacterial species with MIC ranging from 0.5 to 2.0 mg/mL.