Synthesis and evaluation of antimicrobial activity of new derivatives of acetylamides formed from substituted aroilacetonitrilas

• Grant number: 17/00666-0
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: May 01, 2018
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Jan Carlo Morais Oliveira Bertassoni Delorenzi
• Grantee: Jan Carlo Morais Oliveira Bertassoni Delorenzi
• Company: Neguebe Química e Biológica Ltda
• City: São Paulo

Abstract

The acetylamides are obtained from substituted aroilacetonitrilas. From these acetylamides the halogenations reactions are conducted to the introduction of one or two halogen atoms on the in the carbon chain and thus increase the antimicrobial potential of these compounds. The acetylamides react with phosphorus oxychloride and dimethylformamide to form the chlorovinylaldeydes, to be processed by Knoevenagel condensation in push-pull butadienes, high reactive and antimicrobial potential. Starting from dihalogenated acetylamides is possible the substitution of a halogen atom by reaction with derivatives of alcohols, thiols and amines, while maintaining the structure of monohalogenated acetylamides , which increases the antimicrobial potential of these new compounds. The purity of the compounds will be evaluated by high-performance liquid chromatography (HLPC). Once pure, they will be sent to the spectroscopic characterization and organic elemental analysis. Biological assessments will be made through a broad screening of the compounds obtained, in order to corroborate the predictions from molecular design. In the antimicrobial evaluation there will be used a panel of 25 strains of Gram-positive and gram-negative bacteria of clinical interest, through the use of the microdilution method with subsequent confirmation in Petri dishes, determining thus the minimum inhibitory concentration (MIC) of 100% of bacterial growth. In silico theoretical evaluations will be preformed. For compounds with higher antimicrobial potency there will be applied in vitro antibacterial assessments and cytotoxicity evaluations. The study will be conducted following the recommendations from International Regulatory Agencies and ANVISA, as well as the Good Laboratory Practices (GLP). It is intended, therefore, to evaluate the antimicrobial potential of innovative molecules within the regulatory standards that allow for a future registration as drugs. The novel compounds planned in this design are not recovered through a search in SciFinder database, which can allow the submission of two patents. (AU)