Design, synthesis and biological activities of echinopsine derivatives containing acylhydrazone moiety

Abstract

Based on the broad-spectrum biological activities of echinopsine and acylhydrazones, a series of echinopsine derivatives containing acylhydrazone moieties have been designed, synthesized and their biological activities were evaluated for the first time. The bioassay results indicated that most of the compounds showed moderate to good antiviral activities against tobacco mosaic virus (TMV), among which echinopsine (I) (inactivation activity, 49.5 ± 4.4%; curative activity, 46.1 ± 1.5%; protection activity, 42.6 ± 2.3%) and its derivatives 1 (inactivation activity, 44.9 ± 4.6%; curative activity, 39.8 ± 2.6%; protection activity, 47.3 ± 4.3%), 3 (inactivation activity, 47.9 ± 0.9%; curative activity, 43.7 ± 3.1%; protection activity, 44.6 ± 3.3%), 7 (inactivation activity, 46.2 ± 1.6%; curative activity, 45.0 ± 3.7%; protection activity, 41.7 ± 0.9%) showed higher anti-TMV activity in vivo at 500 mg/L than commercial ribavirin (inactivation activity, 38.9 ± 1.4%; curative activity, 39.2 ± 1.8%; protection activity, 36.4 ± 3.4%). Some compounds exhibited insecticidal activities against Plutella xylostella, Mythimna separate and Spodoptera frugiperda. Especially, compounds 7 and 27 displayed excellent insecticidal activities against Plutella xylostell (mortality 67 ± 6% and 53 ± 6%) even at 0.1 mg/L. Additionally, most echinopsine derivatives exhibited high fungicidal activities against Physalospora piricola and Sclerotinia sclerotiorum.

4-Hydroxybenzoic Acid-Based Hydrazide–Hydrazones as Potent Growth Inhibition Agents of Laccase-Producing Phytopathogenic Fungi That Are Useful in the Protection of Oilseed Crops

“…Some antifungal properties were found for molecules bearing naturally occurring echinospine alkaloid, 1-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide which was combined with substituted phenyl or heterocyclic aldehyde fragments. Two molecules, namely (E)-N ′ -(3,4-dimethoxybenzylidene)-1-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide and (E)-N ′ -((1H-indol-2-yl)methylene)-1-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide, caused more than 80% of S. sclerotiorum growth inhibition [55]. In the screening study, the derivatives of indole diketopiperazine with acyl hydrazones containing 4-substituted trifluoromethylbeznaldehyde and tert-butylbenzaldehyde fragment as well as 3-chloro and 2,3-dichlorobenzaldehyde fragments exhibited more than 80% and 50% of antifungal activity against S. sclerotiorum and B. cinerea, respectively [54].…”

“…An alkaloid from Echinops sphaerocephalus L.-echinopsine and their hydrazide-hydrazone derivative were examined as fungicidal compounds. The 4-hydroxybenzaldehyde derivative VII at a concentration of 50 µg/mL showed very good activity against phytopathogenic fungi: Sclerotinia sclerotiorum and Magnaporthe grisea [55]. The indole derivative diketopiperazine acylhydrazone and 3,5-di-tert-butyl- 4-hydroxybenzaldehyde (VIII) showed high inhibitory activity on tobacco mosaic virus (TMV), comparable to the pesticide ningnanmycin, and moderate activity on diamondback moth (Plutella xylostella) and mosquito (Culex pipiens pallens) larvae [56].…”

“…The above examples demonstrate a broad spectrum of hydrazone activity in different biological areas. Interest in this class of compounds is still growing in plant fungicide development [53][54][55][56].…”

Quinoline Derivatives in Discovery and Development of Pesticides

“…Based on this, compounds 39 and 40 were designed and synthesized, and they both showed good fungicidal activity . In addition, quinolinones 41 – 44 showed good fungicidal activity. − For example, compound 44 showed 89.0% inhibition against Rhizoctonia cerealis at 50 mg/L. Compounds 45 and 46 had the same scaffold structure; however, they had weaker fungicidal activity .…”

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field

“…Cui et al 74 designed and synthesized a series of echinocandin derivatives 68 containing an acylhydrazone moiety and performed antifungal activity assays. The results showed that the compounds exhibited weak to moderate fungicidal activity.…”