Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids.

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.

Synthesis and Evaluation of the in vitro Antimicrobial Activity of Triazoles, Morpholines and Thiosemicarbazones.

BACKGROUND: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones. METHODS: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method. RESULTS: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli. CONCLUSION: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs.

Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents.

Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to first and second line therapies has boosted the search for new and effective antifungal agents. In this study, we show the in vitro anti-Candida activity of fifteen synthetic chalcone analogs and their antifungal potential in an in vivo model of VVC. Chalcone 12 showed potent antifungal effects, being able to inhibit the growth of Candida spp. at a concentration of 15.6 µg mL-1. In addition, mechanism of action studies have indicated the ergosterol fungal membrane as the target of this compound. Despite a considerable antifungal activity, the chalcone 12 showed high cytotoxicity in kidney cells lineages. Moreover, this compound was able to reduce Candida-associated virulence, impairing yeast-hyphal transition in C. albicans. An in vivo model of VVC showed that chalcone 12 significantly reduces the fungal load. Taken together, these findings showed that the chalcone 12 is a potent anti-Candida agent in vitro beyond of contribute to improve the fungal infection in a model of CVV. However, it showed low selectivity and high toxicity, suggesting molecular modifications to minimize these proprieties.

Antibacterial activity of Lamiaceae plant extracts in clinical isolates of multidrug-resistant bacteria.

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.