Síntese, caracterização e estudo da atividade fungicida e antitumoral de novas dialquilfosfonilacilidrazonas

Abstract

In This work is shown the synthesis of novel dialkylphosphorylacylhydrazones that occurs in 3 reaction steps: the first step consisted in the synthesis of different dialkyl acetate phosphonoacetates obtained by the reaction of the ethyl bromoacetate with the trialkyl phosphite of interest. The second step was the synthesis of acetic diethoxyphosphonylhydrazides which occured by reaction between dialkyl phosphonoacetates synthesized and hydrazine. The third and final ones occured by the condensation of acetic diethoxyphosphonylhydrazides with different heterocyclic aldehydes. The compounds obtained were fullycharacterized by 1-H and 13-C and 31-P NMR, infrared (IR) and mass spectrometry (MS). In total, 17 novel compounds, namely one to 17, respectively, were obtained with diastereoisomeric mixture of preferential conformation E. The fungicidal activity of the molecule synthesized was performed against plant pathogens responsible for postharvest diseases of economic importance such as Pilidium sp., Alternaria sp., Penicilium sp. and Colletotrichum gloeosporioides, however, they did not present fungicidal activity in the evaluated fungi. The compounds were further tested agaist melanoma cells, for the purpose of verify whether they have any activity in tumor growth of melanoma cells with only compounds 2 and 10 showed some biological activity, although relatively low. After synthesis and purification of the synthesized compounds, they are checked against the acetylcholinesterase enzyme activity, used as indicator of toxicity of organophosphorus compounds. The AChE enzyme inhibition assay has shown that compound 2 does not inhibit the enzyme along with compounds 3, 7, 8 and 16 while compound 13 in addition to compound 9 strongly inhibits AChE and showing even hight inhibitory activity than the standard used, the Propoxur