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8 pages, 1636 KiB

Open AccessCommunication

Synthesis and Oxidative Degradation of Leucine-Based Poly(diacylhydrazine)

by Kanda Wongwailikhit, Ratha Suwannakeeree and Nobuhiro Kihara

Polymers 2024, 16(9), 1222; https://doi.org/10.3390/polym16091222 - 27 Apr 2024

Viewed by 1469

Diacylhydrazine is thermally and chemically stable, and it remains inert to oxygen even at high temperatures. However, it is rapidly oxidized by sodium hypochlorite, leading to its decomposition into carboxylic acid and nitrogen gas. In the synthesis of a novel poly(diacylhydrazine) as an [...] Read more.

Diacylhydrazine is thermally and chemically stable, and it remains inert to oxygen even at high temperatures. However, it is rapidly oxidized by sodium hypochlorite, leading to its decomposition into carboxylic acid and nitrogen gas. In the synthesis of a novel poly(diacylhydrazine) as an oxidatively degradable polymer, L-leucine methyl ester is acylated by terephthaloyl chloride. Subsequent hydrazination yields a bishydrazide monomer. The oxidative coupling polymerization of this monomer produces poly(diacylhydrazine). The molecular structures of the products are confirmed by an ¹H NMR analysis. A polymodal molecular weight distribution and a large polydispersity index are observed by GPC in all cases. A 10% weight loss temperature is noted at 286 °C in air by TGA. The obtained polymer is not oxidized by oxygen. No glass transition is observed below the decomposition temperature. Upon the treatment of the poly(diacylhydrazine) with sodium hypochlorite solution, decomposition occurs rapidly, resulting in monomeric carboxylic acid and nitrogen gas. The L-leucine-based poly(diacylhydrazine) serves as a novel on-demand degradable polymer with high levels of thermal and chemical stability during usage. Full article

(This article belongs to the Collection Design and Synthesis of Polymers)

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23 pages, 5853 KiB

Open AccessArticle

Synthesis of 2-Amino-N′-aroyl(het)arylhydrazides, DNA Photocleavage, Molecular Docking and Cytotoxicity Studies against Melanoma CarB Cell Lines

by Achilleas Mitrakas, Maria-Eleni K. Stathopoulou, Chrysoula Mikra, Chrystalla Konstantinou, Stergios Rizos, Stella Malichetoudi, Alexandros E. Koumbis, Maria Koffa and Konstantina C. Fylaktakidou

Molecules 2024, 29(3), 647; https://doi.org/10.3390/molecules29030647 - 30 Jan 2024

Cited by 1 | Viewed by 2036

Abstract

Diacylhydrazine bridged anthranilic acids with aryl and heteroaryl domains have been synthesized as the open flexible scaffold of arylamide quinazolinones in order to investigate flexibility versus rigidity towards DNA photocleavage and sensitivity. Most of the compounds have been synthesized via the in situ [...] Read more.

Diacylhydrazine bridged anthranilic acids with aryl and heteroaryl domains have been synthesized as the open flexible scaffold of arylamide quinazolinones in order to investigate flexibility versus rigidity towards DNA photocleavage and sensitivity. Most of the compounds have been synthesized via the in situ formation of their anthraniloyl chloride and subsequent reaction with the desired hydrazide and were obtained as precipitates, in moderate yields. All compounds showed high UV-A light absorption and are eligible for DNA photocleavage studies under this “harmless” irradiation. Despite their reduced UV-B light absorption, a first screening indicated the necessity of a halogen at the p-position in relation to the amine group and the lack of an electron-withdrawing group on the aryl group. These characteristics, in general, remained under UV-A light, rendering these compounds as a novel class of UV-A-triggered DNA photocleavers. The best photocleaver, the compound 9, was active at concentrations as low as 2 μΜ. The 5-Nitro-anthranilic derivatives were inactive, giving the opposite results to their related rigid quinazolinones. Molecular docking studies with DNA showed possible interaction sites, whereas cytotoxicity experiments indicated the iodo derivative 17 as a potent cytotoxic agent and the compound 9 as a slight phototoxic compound. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential II)

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15 pages, 1403 KiB

Open AccessArticle

Microwave-Assisted Synthesis of Unsymmetrical 5-Phenyl-1,3,4-oxadiazoles Containing Bis(carboxymethyl)amino Group

by Marcin Łuczyński and Agnieszka Kudelko

Appl. Sci. 2023, 13(22), 12427; https://doi.org/10.3390/app132212427 - 17 Nov 2023

Cited by 1 | Viewed by 1947

Abstract

New derivatives of 5-phenyl-1,3,4-oxadiazole substituted at position 2 with (bromomethyl)phenyl or bromoalkyl groups were obtained via microwave-assisted cyclodehydration of unsymmetrical N,N′-diacylhydrazines. Then, bromine-containing oxadiazoles were substituted with diisopropyl iminodiacetate, yielding the corresponding ester derivatives, which were subsequently hydrolyzed in an aqueous methanol [...] Read more.

New derivatives of 5-phenyl-1,3,4-oxadiazole substituted at position 2 with (bromomethyl)phenyl or bromoalkyl groups were obtained via microwave-assisted cyclodehydration of unsymmetrical N,N′-diacylhydrazines. Then, bromine-containing oxadiazoles were substituted with diisopropyl iminodiacetate, yielding the corresponding ester derivatives, which were subsequently hydrolyzed in an aqueous methanol solution. The cleavage of the ester group resulted in the formation of the appropriate 5-phenyl-1,3,4-oxadiazoles bearing bis(carboxymethyl)amino groups in satisfactory yields. The structures of all products were confirmed by typical spectroscopic methods including 1H and 13C NMR, and HRMS. Full article

(This article belongs to the Section Chemical and Molecular Sciences)

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16 pages, 6046 KiB

Open AccessArticle

Discovery of Simple Diacylhydrazine-Functionalized Cinnamic Acid Derivatives as Potential Microtubule Stabilizers

by Xiang Zhou, Yi-Hong Fu, Ya-Yu Zou, Jiao Meng, Gui-Ping Ou-Yang, Qiang-Sheng Ge and Zhen-Chao Wang

Int. J. Mol. Sci. 2022, 23(20), 12365; https://doi.org/10.3390/ijms232012365 - 15 Oct 2022

Cited by 10 | Viewed by 2268

Abstract

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. [...] Read more.

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. Notably, compound I₂₃ exhibited the best antiproliferative activity against three cancer lines with IC₅₀ values ranging from 3.36 to 5.99 μM and concurrently afforded a lower cytotoxicity towards the NRK-52E cells. Anticancer mechanism investigations suggested that the highly bioactive compound I₂₃ could potentially promote the protofilament assembly of tubulin, thus eventually leading to the stagnation of the G2/M phase cell cycle of HepG2 cells. Moreover, compound I₂₃ also disrupted cancer cell migration and significantly induced HepG2 cells apoptosis in a dosage-dependent manner. Additionally, the in silico analysis indicated that compound I₂₃ exhibited an acceptable pharmacokinetic profile. Overall, these easily prepared N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives could serve as potential microtubule-interacting agents, probably as novel microtubule-stabilizers. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

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10 pages, 4745 KiB

Open AccessArticle

Synthesis of N,O-Chelating Hydrazidopalladium Complexes from 1,2-Bis(trifluoroacetyl)hydrazine

by Yoshihito Kayaki, Tomohiro Hayakawa and Takao Ikariya

Inorganics 2021, 9(10), 76; https://doi.org/10.3390/inorganics9100076 - 7 Oct 2021

Cited by 1 | Viewed by 3109

Abstract

N,O-chelating dicarbonylhydrazido-palladium complexes were synthesized by treatment of 1,2-bis(trifluoroacetyl)hydrazine with a mixture of a Pd(0) source, [Pd(dba)₂] (DBA = dibenzylideneacetone), and four-electron donors including 1,3-bis(diphenylphosphino)propane (DPPP), N,N,N’,N’-tetramethylethylenediamine (TMEDA), and two equivalents [...] Read more.

N,O-chelating dicarbonylhydrazido-palladium complexes were synthesized by treatment of 1,2-bis(trifluoroacetyl)hydrazine with a mixture of a Pd(0) source, [Pd(dba)₂] (DBA = dibenzylideneacetone), and four-electron donors including 1,3-bis(diphenylphosphino)propane (DPPP), N,N,N’,N’-tetramethylethylenediamine (TMEDA), and two equivalents of triphenylphosphine. The same products from DPPP and TMEDA could be obtained alternatively by using Pd(OAc)₂ through deprotonation of the diacylhydrazine. The five-membered chelate structure was confirmed by NMR spectra and X-ray crystal structure determination. The X-ray structures indicate that the products are formally considered as Pd(II) complexes with a hydrazido(2–) ligand. In the case of the triphenylphosphine-coordinated complex, a fluxional behavior in dichloromethane-d₂ was observed by variable temperature NMR experiments, possibly due to structural changes between the square planar and pseudo-tetrahedral geometries. Full article

(This article belongs to the Section Organometallic Chemistry)

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21 pages, 4681 KiB

Open AccessArticle

Antinociceptive and Cytotoxic Activity of Opioid Peptides with Hydrazone and Hydrazide Moieties at the C-Terminus

by Jolanta Dyniewicz, Piotr F. J. Lipiński, Piotr Kosson, Marta Bochyńska-Czyż, Joanna Matalińska and Aleksandra Misicka

Molecules 2020, 25(15), 3429; https://doi.org/10.3390/molecules25153429 - 28 Jul 2020

Cited by 13 | Viewed by 3349

Abstract

In the present contribution, we analyze the influence that C-terminal extension of short opioid peptide sequences by organic fragments has on receptor affinity, in vivo analgesic activity, and antimelanoma properties. The considered fragments were based on either N-acylhydrazone (NAH) or N′-acylhydrazide [...] Read more.

In the present contribution, we analyze the influence that C-terminal extension of short opioid peptide sequences by organic fragments has on receptor affinity, in vivo analgesic activity, and antimelanoma properties. The considered fragments were based on either N-acylhydrazone (NAH) or N′-acylhydrazide motifs combined with the 3,5-bis(trifluoromethyl)phenyl moiety. Eleven novel compounds were synthesized and subject to biological evaluation. The analyzed compounds exhibit a diversified range of affinities for the µ opioid receptor (MOR), rather low δ opioid receptor (DOR) affinities, and no appreciable neurokinin-1 receptor binding. In three out of four pairs, N-acylhydrazone-based derivatives bind MOR better than their N’-acylhydrazide counterparts. The best of the novel derivatives have similar low nanomolar MOR binding affinity as the reference opioids, such as morphine and biphalin. The obtained order of MOR affinities was compared to the results of molecular docking. In vivo, four tested compounds turned out to be relatively strong analgesics. Finally, the NAH-based analogues reduce the number of melanoma cells in cell culture, while their N′-acylhydrazide counterparts do not. The antimelanoma properties are roughly correlated to the lipophilicity of the compounds. Full article

(This article belongs to the Special Issue Advances in Research of Short Peptides)

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12 pages, 1875 KiB

Open AccessArticle

(R)-2-Phenyl-4,5-Dihydrothiazole-4-Carboxamide Derivatives Containing a Diacylhydrazine Group: Synthesis, Biological Evaluation, and SARs

by Feng-Yun Li, Jing-Bo Liu, Jia-Ning Gong and Gen Li

Molecules 2019, 24(24), 4440; https://doi.org/10.3390/molecules24244440 - 4 Dec 2019

Cited by 6 | Viewed by 3082

Abstract

A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, ¹H NMR, ¹³C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated. The antifungal activity result indicated that [...] Read more.

A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, ¹H NMR, ¹³C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated. The antifungal activity result indicated that most title compounds against Cercospora arachidicola, Alternaria solani, Phytophthora capsici, and Physalospora piricola exhibited apparent antifungal activities at 50 mg/L, and better than chlorothalonil or carbendazim. The EC₅₀ values of (R)-N’-benzoyl-2-(4-chlorophenyl)-4,5-dihydrothiazole-4-carbohydrazide (I-5) against six tested phytopathogenic fungi were comparable to those of chlorothalonil. The CoMSIA model showed that a proper hydrophilic group in the R¹ position, as well as a proper hydrophilic and electron-donating group in the R² position, could improve the antifungal activity against Physalospora piricola, which contributed to the further optimization of the structures. Meanwhile, most title compounds displayed good insecticidal activities, especially compound (R)-N’-(4-nitrobenzoyl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carbohydrazide (III-3). The insecticidal mechanism results indicated that compound III-3 can serve as effective insect Ca²⁺ level modulators by disrupting the cellular calcium homeostasis in Mythimna separata. Full article

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8 pages, 2107 KiB

Open AccessCommunication

Synthesis and X-ray Crystal Structure of N’-Cyano-N,N’-dimethyl-4-nitrobenzohydrazide

by Reik Löser, Riccardo Pitzschler and Martin Köckerling

Crystals 2017, 7(10), 290; https://doi.org/10.3390/cryst7100290 - 26 Sep 2017

Cited by 6 | Viewed by 5125

Abstract

Using a two-step procedure, N’-cyano-N,N’-dimethyl-4-nitrobenzohydrazide was synthesized. The structure was established using single crystal X-ray diffraction. It crystalized in the orthorhombic space group P2₁2₁2₁ where a = 8.1974(6), b = 10.6696(7), and [...] Read more.

Using a two-step procedure, N’-cyano-N,N’-dimethyl-4-nitrobenzohydrazide was synthesized. The structure was established using single crystal X-ray diffraction. It crystalized in the orthorhombic space group P2₁2₁2₁ where a = 8.1974(6), b = 10.6696(7), and c = 12.9766(8) Å. The first reported crystal structure of an acyclic cyanohydrazide is discussed with a focus on the geometry of the hydrazide moiety, but intermolecular contacts in the crystal are also considered. Full article

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8 pages, 1651 KiB

Open AccessArticle

Synthesis, Crystal Structure, DFT Study of m-Methoxy-N′-(3-Methoxybenzoyl)-N-Phenylbenzohydrazide

by Ifzan Arshad, Javeria Yameen, Aamer Saeed, Jonathan M. White and Fernando Albericio

Crystals 2017, 7(1), 19; https://doi.org/10.3390/cryst7010019 - 12 Jan 2017

Cited by 7 | Viewed by 5131

Abstract

The crystal structure of m-methoxy-N′-(m-anisoyl)-N-phenylbenzohydrazide has been determined by means of single-crystal X-ray diffraction. The title compound crystallizes in the monoclinic space group P 21/c with unit cell parameters: a = 8.7338(1), b = 24.5602(3), c [...] Read more.

The crystal structure of m-methoxy-N′-(m-anisoyl)-N-phenylbenzohydrazide has been determined by means of single-crystal X-ray diffraction. The title compound crystallizes in the monoclinic space group P 21/c with unit cell parameters: a = 8.7338(1), b = 24.5602(3), c = 9.6929(1) Å, β = 113.186(2)°, V = 1911.23(4) Å³, Z = 4. The dihedral angles between the mean plane of the central benzene ring and two terminal aromatic rings are 72.44(4)° and 89.90(4)°, respectively. The two methoxyphenyl rings are orthogonal with a dihedral angle of 89.74(4)°. The crystal packing is stabilized by a combination of N–H^…O intermolecular hydrogen bonding and weak intermolecular C–H^…O interactions. The X-ray structure was compared with the optimized counterpart calculated by the B3LYP/6-311G basis set and the results showed that the optimized geometry can reproduce the crystal structure parameters well. Full article

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13 pages, 732 KiB

Open AccessArticle

Design, Synthesis, and Insecticidal Activity of Some Novel Diacylhydrazine and Acylhydrazone Derivatives

by Jialong Sun and Yuanming Zhou

Molecules 2015, 20(4), 5625-5637; https://doi.org/10.3390/molecules20045625 - 30 Mar 2015

Cited by 30 | Viewed by 7158

Abstract

In this study a series of diacylhydrazine and acylhydrazone derivatives were designed and synthesized according to the method of active group combination and the principles of aromatic group bioisosterism. The structures of the novel derivatives were determined on the basis on ¹H-NMR, [...] Read more.

In this study a series of diacylhydrazine and acylhydrazone derivatives were designed and synthesized according to the method of active group combination and the principles of aromatic group bioisosterism. The structures of the novel derivatives were determined on the basis on ¹H-NMR, IR and ESI-MS spectral data. All of the compounds were evaluated for their in vivo insecticidal activity against the third instar larvae of Spodoptera exigua Hiibner, Helicoverpa armigera Hubner, Plutella xyllostella Linnaeus and Pieris rapae Linne, respectively, at a concentration of 10 mg/L. The results showed that all of the derivatives displayed high insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, metaflumizone and tolfenpyrad, and approximately identical insecticidal activity against H. armigera, P. xyllostella and P. rapae as the references metaflumizone and tolfenpyrad. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 692 KiB

Open AccessArticle

Design, Synthesis and Insecticidal Activity of Novel Phenylurea Derivatives

by Jialong Sun and Yuanming Zhou

Molecules 2015, 20(3), 5050-5061; https://doi.org/10.3390/molecules20035050 - 19 Mar 2015

Cited by 1 | Viewed by 5925

Abstract

A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and ¹ [...] Read more.

A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and ¹H-NMR spectral data. All of the compounds were evaluated for the insecticidal activity against the third instars larvae of Spodoptera exigua Hiibner, Plutella xyllostella Linnaeus, Helicoverpa armigera Hubner and Pieris rapae Linne respectively, at the concentration of 10 mg/L. The results showed that all of the derivatives displayed strong insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, chlorbenzuron and metaflumizone. Among the synthesized compounds, 3b, 3d, 3f, 4b and 4g displayed broad spectrum insecticidal activity. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 430 KiB

Open AccessArticle

Design, Synthesis, Biological Activities and 3D-QSAR of New N,N'-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moieties

by Guo-Xiang Sun, Zhao-Hui Sun, Ming-Yan Yang, Xing-Hai Liu, Yi Ma and Yun-Yang Wei

Molecules 2013, 18(12), 14876-14891; https://doi.org/10.3390/molecules181214876 - 3 Dec 2013

Cited by 20 | Viewed by 5691

Abstract

A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by ¹H-NMR, MS and elemental analysis. The herbicidal activities and plant growth regulating activity of these N,N'-diacylhydrazines were evaluated. The herbicidal activity results showed [...] Read more.

A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by ¹H-NMR, MS and elemental analysis. The herbicidal activities and plant growth regulating activity of these N,N'-diacylhydrazines were evaluated. The herbicidal activity results showed that most of these N,N'-diacyl-hydrazines showed excellent in vivo activities against Echinochloa crus-galli, Digitaria sanguinalis, Brassica napus, Amaranthus retroflerus. Most of them exhibited higher herbicidal activities against dicotyledonous weeds than monocotyledonous weeds. To further investigate the structure-activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of herbicidal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this work. Full article

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16 pages, 471 KiB

Open AccessArticle

Design, Synthesis, Antifungal Activities and 3D-QSAR of New N,N'-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moiety

by Na-Bo Sun, Yan-Xia Shi, Xing-Hai Liu, Yi Ma, Cheng-Xia Tan, Jian-Quan Weng, Jian-Zhong Jin and Bao-Ju Li

Int. J. Mol. Sci. 2013, 14(11), 21741-21756; https://doi.org/10.3390/ijms141121741 - 1 Nov 2013

Cited by 22 | Viewed by 6277

Abstract

A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by ¹H-NMR, mass spectra (MS) and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most [...] Read more.

A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by ¹H-NMR, mass spectra (MS) and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N'-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC₅₀) of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure–activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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