Design, Synthesis and Bioactivity Evaluation of Novel β-carboline 1,3,4-oxadiazole Derivatives

Zhang, Zhijun; Zhang, Jingjing; Jiang, Zongyong; Zhong, Guohua

doi:10.3390/molecules22111811

Cited by 14 publications

(12 citation statements)

References 33 publications

(37 reference statements)

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“…The 2-thioxo-1,3,4-oxadiazole derivatives with special biological activities have attracted more and more attention and have been widely used in drug and pesticide molecular design in recent years [ 37 , 38 , 39 , 40 ]. Our previous study demonstrated that β-carboline 1,3,4-oxadiazoles which introduced the 2-thioxo-1,3,4-oxadiazole groups into β-carboline scaffolds at the C-3 position also exhibited significant cytotoxicity against Spodoptera frugiperda Sf9 cells [ 41 ]. In the present study, harmine and the novel ZC-14 bearing substituents in positions 1 and 3 of the β-carboline ring have been evaluated insecticides against Sf9 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Harmine was purchased from Sigma (Santa clara, CA, USA) and the derivative ZC-14 [1-(2-naphthyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carboline] was synthesized in our lab ( Figure 1 ). ZC-14 was synthesized using harmine as the lead compound and position 1 replaced with naphthalen and position 3 replaced by 2-thioxo-1,3,4-oxadiazole group [ 41 ]. Dimethyl sulfoxide (DMSO) of analytical reagent purchased from Sigma was used as the solvent for dissolving harmine and ZC-14.…”

Section: Methodsmentioning

confidence: 99%

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Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

Zhang

Shu

et al. 2018

IJMS

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Harmine, one of the natural β-carboline alkaloids extracted from Peganum harmala L., exhibits broad spectrum but limited insecticidal ability against many pests. So there is an urgent need to synthesize novel derivatives with high efficiency. In the present study, a new synthetic compound, [1-(2-naphthyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carboline] (ZC-14), showed a strong proliferation inhibition effect against the Spodoptera frugiperda Sf9 cell line in a dose-dependent manner. Simultaneously, apoptosis induced by 7.5 μg/mL ZC-14 was confirmed with physiological and biochemical evidence, including typical apoptosis characteristics with shrinkage, apoptotic bodies, nuclear condensation/fragmentation, a clear DNA ladder, and a series of apoptotic rates. In addition, mitochondria were confirmed to be involved in apoptosis induced by ZC-14 accompanied with the loss of mitochondrial membrane potential (Δψm), the release of cytochrome c from mitochondria into the cytosol and increased expression of cleaved-caspase-3. However, harmine could not induce apoptosis at the same concentration. In summary, these data indicated that compound ZC-14 has a higher cytotoxicity than harmine against Sf9 cells. Besides, it exhibited an anti-proliferative effect in Sf9 cells via inducing apoptosis in which the mitochondrial apoptotic pathway plays a crucial role.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

Zhang

Shu

et al. 2018

IJMS

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“…Subsequently, rearrangment of this intermediate in various alcohols yielded the substituted indole-2-carbamates 15 -18 [20]. Compound 19 was prepared according to our previously reported procedure [21]. N-benzylation of indole was accomplished using 2-chloro-5-chloromethylpyridine in the presence of sodium hydride, furnishing 1-(6-chloro-3pyridylmethyl)-1H-indole 28.…”

Section: Chemistrymentioning

confidence: 99%

“…Of these compounds, indole (7, EC 50 = 25.56 µg/mL) displayed superior fungicidal activity, and was 7-fold as potent as validamycin A (EC 50 = 183.00 µg/mL). Additionally, it can be seen quite clearly that the structural changes in general were detrimental to activity and no favorable substitution could be found for the 2-or 3-position, even after extensive probing with a variety of diverse groups (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). These findings implied that indole was a potent fungicidal template for further modification and derivatization.…”

Section: Chemistrymentioning

confidence: 99%

Simplification of Natural β-Carboline Alkaloids to Obtain Indole Derivatives as Potent Fungicides against Rice Sheath Blight

et al. 2020

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The increasing resistance of rice sheath blight caused by Rhizoctonia solani highlights the need for highly effective and environmentally benign agents. Natural β-carboline alkaloids were simplified to obtain a series of indole derivatives, and their fungicidal activity and preliminary mode of action against R. solani were also evaluated. The initial hit indole (7) displayed significant fungicidal activity with an EC50 value of 25.56 μg/mL, and was selected for further optimization. Importantly, compound 55, the most active compound, had an EC50 value of 0.62 μg/mL, and approximately 300-fold more potent than validamycin A (EC50 = 183.00 μg/mL). In vivo bioassay also demonstrated that compound 55 showed better fungicidal activities than validamycin A. Moreover, the mechanism studies revealed that compound 55 not only caused remarkable morphological and structural alterations of R. solani hyphae, but also induced the loss of mitochondrial membrane potential and interfered with DNA synthesis. Therefore, compound 55 showed superior fungicidal activity against R. solani, and the elucidated mode of action supported the potential application of compound 55 against rice sheath blight.

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“…The reported biological applications of β-carboline alkaloids include sedative and anxiolytic [ 6 ], antitumor [ 7 , 8 ], antimalarial [ 8 ], antiparasitic [ 9 ], anti-HIV [ 10 ] agents, and other pharmacological activities. As for pest management, the extracts of Peganum harmala L. plant species containing a mixture of harmine, harmaline, and norharman, as well as their derivatives, had been proven to have excellent insecticidal, fungicidal, and plant growth regulatory properties [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. In our previous work [ 18 ], we found that 9-fluorosubstituted-harmine displayed higher fungicidal activities against Rhizoctonia solani , Rape sclerotinia rot, and Alternaria kikuchiana Tanaka.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Antifungal Activity of Novel Aryl-1,2,3-Triazole-β-Carboline Hybrids

et al. 2018

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The copper catalytic azide and terminal alkyne cycloaddition reaction, namely “click chemistry”, gives a new and convenient way to create l,4-disubstitutd-l,2,3-triazoles. In this work, 2-pyrrolecarbaldiminato–Cu(II) complexes were established as efficient catalysts for the three-component 1,3-dipolar cycloaddition reaction of arylboronic acid and sodium azide (NaN3) with terminal alkynes in ethanol at room temperature to 50 °C, 1,4-disubstituted 1,2,3-triazoles were synthesized. Following the optimized protocol, two series of new aryl-1,2,3-triazole-β-carboline hybrids have been designed and synthesized, and the chemical structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS). All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Fusarium oxysporum, Botrytis cinerea Pers., sunflower sclerotinia rot, and rape sclerotinia rot by mycelia growth inhibition assay at 50 μg/mL. The antifungal evaluation of the novel hybrids showed that, among the tested compounds, 5a, 5b, 5c, and 9b showed good antifungal activity against sunflower sclerotinia rot. Specifically, compound 9b also exhibited high broad-spectrum fungicidal against all the tested fungi with inhibition rates of 58.3%, 18.52%, 63.07%, 84.47%, and 81.23%. However, for F. oxysporum, all the target compounds showed no in vitro antifungal activities with an inhibition rate lower than 20%. These results provide an encouraging framework that could lead to the development of potent novel antifungal agents.

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Design, Synthesis and Bioactivity Evaluation of Novel β-carboline 1,3,4-oxadiazole Derivatives

Cited by 14 publications

References 33 publications

Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

Simplification of Natural β-Carboline Alkaloids to Obtain Indole Derivatives as Potent Fungicides against Rice Sheath Blight

Design, Synthesis, and Antifungal Activity of Novel Aryl-1,2,3-Triazole-β-Carboline Hybrids

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