title: Synthesis, Antifungal Evaluation and In Silico Study of N-(4-Halobenzyl)amides.
abstract: A collection of 32 structurally relatedN-(4-halobenzyl)amides were synthesized from cinnamic and benzoic acids through coupling reactions with 4-halobenzylamines, using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling agent. The compounds were identified by spectroscopic methods such as infrared, ¹H- and13C- Nuclear Magnetic Resonance (NMR) and high-resolution mass spectrometry. The compounds were then submitted to antimicrobial tests by the minimum inhibitory concentration method (MIC) and nystatin was used as a control in the antifungal assays. The purpose of the tests was to evaluate the influence of structural changes in the cinnamic and benzoic acid substructures on the inhibitory activity against strains ofCandida albicans,Candida tropicalis, andCandida krusei. A quantitative structure-activity relationship (QSAR) study with KNIME v. 3.1.0 and Volsurf v. 1.0.7 softwares were realized, showing that descriptors DRDRDR, DRDRAC, L4LgS, IW4 and DD2 influence the antifungal activity of the haloamides. In general, 10 benzamides revealed fungal sensitivity, especially a vanillic amide which enjoyed the lowest MIC. The results demonstrate that a hydroxyl group in theparaposition, and a methoxyl at themetaposition enhance antifungal activity for the amide skeletal structure. In addition, the double bond as a spacer group appears to be important for the activity of amide structures.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil. ricsony_79@yahoo.com.br.
authors.forename: Ricardo Carneiro
authors.initials: RC
authors.lastname: Montes
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil. analuiza_perez@yahoo.com.br.
authors.forename: Ana Luiza A L
authors.initials: AL
authors.lastname: Perez
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil. cassioism@hotmail.com.
authors.forename: Cássio Ilan S
authors.initials: CI
authors.lastname: Medeiros
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil. marianninhaoliveira@yahoo.com.br.
authors.forename: Marianna Oliveira de
authors.initials: MO
authors.lastname: Araújo
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil. edelolima@yahoo.com.br.
authors.forename: Edeltrudes de Oliveira
authors.initials: EO
authors.lastname: Lima
authors.affiliation: Departamento de Química, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil. mtscotti@gmail.com.
authors.forename: Marcus Tullius
authors.initials: MT
authors.lastname: Scotti
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil. damiao_desousa@yahoo.com.br.
authors.forename: Damião Pergentino de
authors.initials: DP
authors.lastname: Sousa
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D003198:Computer Simulation; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D066244:Proton Magnetic Resonance Spectroscopy; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000577:Amides; D000935:Antifungal Agents
keywords: Candida; antimicrobial activity; halogenated amides; vanillic acid derivatives