The effects of coumaric acid and its analogues on melanin growth and biosynthesis in the opportunistic pathogen Cryptococcus neoforms

• Grant number: 22/02622-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: August 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Renata Castiglioni Pascon
• Grantee: Vivian Jugni Silva
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The yeast Cryptococcus neoformans is an opportunistic fungal pathogen that can cause meningitis and pneumonia in immunocompromised individuals, especially patients with AIDS/HIV, transplanted and undergoing chemotherapy. In general, Invasive Fungal Infections (IFIs) are difficult to treat, because the antifungals used in the clinic, in addition to being scarce, do not have a high selective toxicity and are used in high doses, being hepatotoxic and nephrotoxic in patients who need treatment with these drugs. One of the ways to overcome the disadvantages of antifungal therapy is through the combination of drugs that make it possible to reduce the doses of classic antifungals such as fluconazole and amphotericin B. This combined therapy strategy targets the virulence factors that allow the colonization of the pathogen in the host and the escape mechanisms of the immune system. Data previously obtained by our group showed that inhibition of melanin biosynthesis by the use of coumaric acid derivatives leads to greater sensitivity of C. neoformans to amphotericin B. The combined use of two analogues reduced the minimum inhibitory concentration of this substance by up to 6 times. antifungal, demonstrating the potential of this strategy. For this reason, in this work, we will evaluate other compounds analogous to coumaric acid and their interaction with drugs such as Amphotericin B and Fluconazole, in addition to the inhibition of yeast growth and melanization capacity