Synthesis, antimicrobial and cytotoxicity studies of some novel modified Strobilurin derivatives

Abstract

Uma série de novas 3-isoxazolinas substituídas, derivadas do metil-3-metóxi-2-(4-oxo-3,4-diidroftalazin-1-il)prop-2-enoato foram estudadas e sintetizadas a partir do metil-(4-oxo-3,4-diidroftalazin-1-il)acetato, o qual foi preparado a partir do anidrido ftálico. As estruturas dos novos compostos sintetizados foram caracterizadas por dados espectrais e suas atividades antimicrobianas e citotóxicas estudadas. Vários desses compostos mostraram boa atividade antimicrobiana.A series of some new 3-isoxazoline substituted methyl-3-methoxy-2-(4-oxo-3,4-dihydrophthalazin-1-yl)prop-2-enoate derivatives were designed and synthesized from methyl-(4-oxo-3,4-dihydrophthalazin-1-yl)acetate, which in turn was prepared from phthalic anhydride. The structures of synthesized new compounds were characterized by spectral data and studied for their antimicrobial activities and cytotoxicity. Several of these compounds showed good antimicrobial activity.Keywords: phthalazin-1(2H)-one, β-methoxyacrylate, strobilurins, isoxazoline IntroductionNitrogen-containing heterocyclic molecules constitute the largest portion of chemical entities, which are part of many natural products, fine chemicals, and biologically active pharmaceuticals. Strobilurins and their analogues constitute a large group of compounds that represent a new class of plant-protecting agents 1 that meet all the demands that are made nowadays for pesticides. They exhibit efficacy against a broad-spectrum of fungal diseases, possess significant post-infective activity, and have a unique mode of action. 2 Intensive studies aimed at a search for novel biologically active methoxyacrylate fungicides are currently under way by different manufacturers. 3 Studies on the structure of natural methoxyacrylates have made possible to create a novel class of synthetic fungicides with enhanced stability, high activity, and a broad spectrum of action. β-Methoxyacrylate which is a critical and common structural element of strobilurins, fund use in agrochemical agents, 4 antivirals, 5 antimalarials, 6 and fungicides. 7 There has been extensive industrial development of these compounds and their analogues. 8,9 In finding new β-methoxyacrylate derivatives, we observed that, phthalazines attached to these pharmacophore were not studied. Phthalazin-1(2H)-one derivatives are of considerable interest due to their antidiabetic, 10 antiallergic, 11 vasorelaxant, 12 PDE4 inhibitor, 13 VEGF (vascular endothelial growth factor) receptor tyrosine kinase (for the treatment of cancer), 14 The diverse biological activities of β-methoxyacrylate, phthalazin-1(2H)-one, and isoxazoline pharmacophores envisaged us to plan a new lead compounds that may exhibit wide pharmacological activities. By combining these pharmacophore components in a molecule to give a compact system, we designed and synthesized a series of phthalazin-1(2H)-one derivatives containing β-methoxyacrylate and isoxazoline moieties. Figure 1 reveals a framework of these three important biological active pharmacophore component systems.The synth...

Synthesis, Bioevaluation and Structural Study of Substituted Phthalazin-1(2H)-ones Acting as Antifungal Agents

“…In the course of our on-going screening program for new and selective antifungal compounds, we have previously reported several series of antifungal compounds obtained from natural and synthetic sources [4,5,6,7,8,9]. Considering that some phthalazine derivatives, including some polybrominated compounds [10], 4-benzyl substituted ones [11] and others [12,13,14,15] have been evaluated for their antimicrobial and particularly antifungal activities against yeasts ( Candida and Cryptococcus strains) and Aspergillus spp., we have prepared a series of twenty five differently substituted phthalazin-1-ones to evaluate their antifungal activities against a panel of representative clinically important fungal species. Then, taking into account the antifungal results, conformational and electronic studies on the most interesting compound of the series were carried out.…”

Synthesis and Bio-Evaluation of Natural Butenolides-Acrylate Conjugates

“…The growth inhibition rates were calculated by means of the following equation: I = [(D 0 − D t )/D 0 ] × 100%, where I is the growth inhibition rate (%), D 0 is the blank control colony growth diameter (mm) and D t is the pharmacy treatment colony growth diameter (mm) [21,22,23].…”

Comprehensive Overview of β-Methoxyacrylate Derivatives as Cytochrome bc1 Inhibitors for Novel Pesticide Discovery

“…β-Methoxyacrylate derivatives bind the Qo site of cytochrome bc 1 and block electron transfer between cytochrome b and cytochrome c , which prevents oxidation of NADH and synthesis of ATP, resulting in the inhibition of energy production and thus leading to fungal death (Figure ). On the other hand, as the mitochondrial respiratory chain also widely exists in eukaryotes, the research extends to other types of pesticides, such as acaricides, , insecticides, − and herbicides, − and, drugs such as antitumor, − antimalarial, − and antimicrobial agents. , In addition, some β-methoxyacrylate derivatives could even be used as antiviral agents against plant viruses. − …”