Antifungal activity of natural and synthetic amides from Piper species

Abstract

Extrato de folhas de Piper scutifolium apresentou atividade antifúngica significativa contraCladosporium cladosporioides e C. sphaerospermum e seus principais componentes ativos, piperina, piperlonguminina e corcovadina foram isolados por meio de purificação biomonitorada, apresentando limites de detecção de 1 µg. Foi realizado um estudo da relação estrutura-atividade baseado na síntese de doze análogos com variações no número de insaturações, no padrão de substituição no anel aromático e no grupo amídico. As amidas sem substituintes no anel aromático e com apenas uma ligação dupla foram as mais ativas e os derivados N,N-dietil-substituídos apresentam maior dose-dependência.The antifungal leaves extract from Piper scutifolium was submitted to bioactivity-guided chromatographic separation against Cladosporium cladosporioides and C. sphaerospermum yielding piperine, piperlonguminine and corcovadine as the active principles which displayed a detection limit of 1 µg. Structure-activity relationships were investigated with the preparation of twelve analogs having differences in the number of unsaturations, aromatic ring substituents and in the amide moiety. Analogs having a single double-bond and no substituent in the aromatic ring displayed higher activity, while N,N,-diethyl analogs displayed higher dose-dependent activity. Keywords: Piper, antifungal, analogs, amides IntroductionPiper (Piperaceae) are commonly herbs, shrubs or infrequently trees with over 1000 species described so far mostly on tropical regions. 1 In addition to the high economical value of black pepper (P. nigrum) as a spice, there are several medicinal uses described for different Piper species, including anti-inflammatory, analgesic and treatment of snake-bite. 2,3 Several Piper species have been phytochemicaly investigated 4-6 and a plethora of secondary metabolites has been found including kavalactones, 7,8 lignoids, 9-11 chromenes, 12,13 terpenes, 14,15 prenylated benzoic acids 13,16,17 and also amides as the most characteristic classes of compounds. 18,19 The most prominent example of a Piper amide is piperine, the pungent principle of black pepper (P. nigrum). It was the first natural product isolated from Piper species back in 1819. Piperine and several other amides have shown a variety of biological activity, e.g., antitumoral, [20][21][22] efflux-pump inhibitor, 23-25 insecticidal 19,26-36 and antifungal activity. [37][38][39] The importance of insecticidal activity of Piper amides is considerable and thus several studies have been addressed to investigate possible structureactivity relationships. For instance, isobutylamides have shown high activity against different insects including Musca domestica, 40 Aedes aegypti 36 and A. togoi 41 and compounds bearing methylenedioxyphenyl substituents can act in some cases as synergists for other compounds by interfering with cytochrome P450-mediated detoxifications of insecticides. 34,42,43 In spite of the occurrence of several antifungal amides in plants, 37,38,44,45 the data concerning the m...

Chemical ecology of fruit defence: synergistic and antagonistic interactions among amides from Piper

“…; Marques et al . ; Morandim et al . ), and thus may provide defence against a variety of fruit antagonists.…”

“…In particular, many Piper species are rich in amides, a group of secondary metabolites that play an important ecological role in the defence of leaves against herbivores (Dyer et al 2001Fincher et al 2008;Richards et al 2010), but have not been examined in the context of fruit-frugivore interactions. In laboratory studies, amides have a broad range of bioactivity against insects, fungi and molluscs (Bernard et al 1995;da Silva et al 2002;Yang et al 2002;Navickiene et al 2003;Siddiqui et al 2005;Marques et al 2010;Morandim et al 2010), and thus may provide defence against a variety of fruit antagonists. In a recent study describing the amides in different plant parts of Piper reticulatum (Fig.…”

Chemical similarity and local community assembly in the species rich tropical genus Piper

“…Piper secondary metabolite diversity has been extensively studied and there is an important body of published methods for compound isolation, chemical profiling, and artificial synthesis (Parmar et al 1997, 1998, Kato and Furlan 2007. Furthermore, the effects of their secondary chemistry on herbivores, pathogens, and seed dispersal are well documented (Dyer et al 2001, Mikich et al 2003, Fincher et al 2008, Marques et al 2010, Richards et al 2015.…”

Chemometric analysis of ESIMS and NMR data from Piper species

“…[22][23][24][25][26][27][28] Several Piper species are pioneer, and can be found in forest borders and for such reason they are also under risk of depletion by anthropic activities. Thus, the preservation of germplasm is highly desirable but the development of methodology for analyzing and recording the chemical profile of large number of species is also urgently required.…”