Synthesis Of Indole Derivatives And Antifungal Activity And Mechanism Against Candida Albicans

Candida Albicans is one of the most common fungal pathogens of human mucosal skin and invasive fungal infections.Candida albicans plays a key role in human health and disease status,and is the fourth most common cause of hospital acquired infections.With the increasing infection rate of C.albicans,the prevention and treatment of candida albicans has become a hot field of pharmacochemistry and clinical therapeutics.Although there are a variety of anti-candida albicans drugs,but with the continuous emergence of drug-resistant strains and adverse reactions brought by drugs,there is an urgent need for new antifungal drugs or effective treatment strategies.Indole and its derivatives are a class of very important benzoprazole heterocyclic compounds.Recent studies have found that indole derivatives can inhibit the formation of C.albicans biofilm and the development of mycelia,and have good antifungal activity.Based on this,indoles derivatives were designed and synthesized in this paper,and their anti-Candida activity and mechanism were studied,so as to find active lead compounds with further research value,which has very important research significance.In the first chapter,using indole and methyl acrylate as raw materials,20 novel indole and indoline derivatives(S1-S20)were designed and synthesized,and the antifungal activity of compounds S11,S12,S17,S18 and S20 showed good antifungal activity against ATCC10231 FR.In particular,S18 showed strong antifungal activity against FLC-sensitive strains SC5314,ATCC10231,FLC-resistant strains and SC5314 FR.Mechanism studies have shown that S18 can inhibit the growth and development of Candida albicans mycelia and the formation of biofilms through Ras-c AMP-PKA pathway.In Chapter 2,Indole and salicylaldehyde with different substituents are used as raw materials,17 bis(indolyl)methanes derivatives(BI-1-17)with novel structure of phenol were designed and synthesized.Antifungal activity tests showed that most of the derivatives showed good synergistic antifungal effects on sensitive and resistant strains of Candida albicans when combined with FLC.Mechanism studies showed that BI-10 combined with FLC could stimulate ROS production,lead to ROS accumulation,reduce MMP,and change membrane permeability.In Chapter 3,we summarizes the results and characteristics of the work,analyzes the problems in the process of research,and puts forward the prospect of future research.In Chapter 4,the synthesis methods and antibacterial activities of indole derivatives in recent years were reviewed.