New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies

Aly, Ashraf A.; Bräse, Stefan; Hassan, Alaa A.; Mohamed, Nasr K.; El-Haleem, Lamiaa E. Abd; Nieger, Martin; Morsy, Nesrin M.; Abdelhafez, Elshimaa M.

doi:10.3390/molecules25133089

Cited by 14 publications

(21 citation statements)

References 49 publications

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“…Therefore, we are aiming to prepare other classes such as triazolethione and oxadiazole moieties linked to the paracyclophane molecule. Figure 2 summarizes some of the routes utilized to prepare paracyclophanyl-triazole-3-thiones and -paracyclophanyl-2-substituted amino-1,3,4-oxadiazoles from acylhydrazinecarbothioamides [62].…”

Section: Resultsmentioning

confidence: 99%

“…The NMR spectra ( Figure S1-S32) were measured in DMSO-d6 on a Bruker AV-400 spectrometer (Germany), 400 MHz for 1 H, and 100 MHz for 13 C; and the chemical shifts are expressed in (ppm), versus internal tetramethylsilane (TMS) = 0 for 1 H and 13 Compounds 2 and 5-10 were prepared according to the literature [67,68]. Compounds 11a-f were prepared according to the methodology mentioned in reference [62]. (1,4(1,4)-Dibenzenacyclohexaphane-1 2 -yl)hydrazide (1) Under an argon atmosphere, a mixture of ethyl [2.2]paracyclophane-4-carboxylate (8) [39] (5.00 g, 18.0 mmol, 1.00 equiv.)…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported that some paracyclophane-heterocycles such as methyl 2-(2-(4'- [2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI50 and total growth inhibition (TGI) levels, respectively [62]. Therefore, we are aiming to prepare other classes such as triazolethione and oxadiazole moieties linked to the paracyclophane molecule.…”

Section: Introductionmentioning

confidence: 99%

“…More than six decades ago from the discovery of [2.2]paracyclophane, its derivatives have been the subject of particular interest [ 62 , 63 , 64 , 65 ]. Most of the unique properties of these cyclophanes are the result of the rigid framework and the short distance between the two aromatic rings within the [2.2]paracyclophane unit.…”

Section: Introductionmentioning

confidence: 99%

“…-3-thiones and -paracyclophanyl-2-substituted amino-1,3,4-oxadiazoles from acylhydrazinecarbothioamides[62].…”

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confidence: 99%

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Synthesis of New Planar-Chiral Linked [2.2]Paracyclophanes-N-([2.2]-Paracyclophanylcarbamoyl)-4-([2.2]Paracyclophanylcarboxamide, [2.2]Paracyclophanyl-Substituted Triazolthiones and -Substituted Oxadiazoles

et al. 2020

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The manuscript describes the synthesis of new racemic and chiral linked paracyclophane assigned as N-5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carbamoyl)-5’-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carboxamide. The procedure depends upon the reaction of 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)hydrazide with 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)isocyanate. To prepare the homochiral linked paracyclophane of a compound, the enantioselectivity of 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carbaldehyde (enantiomeric purity 60% ee), was oxidized to the corresponding acid, which on chlorination, gave the corresponding acid chloride of [2.2]paracyclophane. Following up on the same procedure applied for the preparation of racemic-carbamoyl and purified by HPLC purification, we succeeded to obtain the target Sp-Sp-N-5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carbamoyl)-5’-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carboxamide. Subjecting N-5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)hydrazide to various isothiocyanates, the corresponding paracyclophanyl-acylthiosemicarbazides were obtained. The latter compounds were then cyclized to a new series of 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)-2,4-dihydro-3H-1,2,4-triazol-3-thiones. 5-(1,4(1,4)-Dibenzenacyclohexaphane-12-yl)-1,3,4-oxadiazol-2-amines were also synthesized in good yields via internal cyclization of the same paracyclophanyl-acylthiosemicarbazides. NMR, IR, and mass spectra (HRMS) were used to elucidate the structure of the obtained products. The X-ray structure analysis was also used as an unambiguous tool to elucidate the structure of the products.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…-3-thiones and -paracyclophanyl-2-substituted amino-1,3,4-oxadiazoles from acylhydrazinecarbothioamides[62].…”

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Synthesis of New Planar-Chiral Linked [2.2]Paracyclophanes-N-([2.2]-Paracyclophanylcarbamoyl)-4-([2.2]Paracyclophanylcarboxamide, [2.2]Paracyclophanyl-Substituted Triazolthiones and -Substituted Oxadiazoles

et al. 2020

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Design, synthesis and Anti‐PVY activity of planar chiral thiourea derivatives incorporated with [2.2]Paracyclophane

Shu,

Lv,

Chen

et al. 2024

Pest Management Science

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BACKGROUNDPotato virus Y (PVY) stands as a prominent representative in the realm of plant viruses. It can inflict severe damage upon Solanaceae plants, leading to global dissemination and substantial economic losses. To discover the new antiviral agents, a class of planar chiral thiourea molecules through the key step of N‐heterocyclic carbene‐catalyzed nitrile formation reaction were synthesized with excellent optical purities for antiviral evaluations against plant virus PVY.RESULTSThe absolute configurations of the planar chiral compounds have exhibited obvious distinctions in the anti‐PVY activities. Notability, compound (S)‐4u exhibited remarkable curative activities against PVY, with the half maximal effective concentration values of 349.3 μg/mL, which was better than that of the ningnanmycin with the EC50 values of 400.8 μg/mL. Additionally, The EC50 value for the protective effects of (S)‐4u was 146.2 μg/mL, which was superior to that of NNM (276.4 μg/mL). Furthermore, the mechanism of action of enantiomers of planar chiral compound 4u was investigated through molecular docking, defensive enzyme activity tests and chlorophyll content tests.CONCLUSIONBiological mechanism studies have demonstrated that the configuration of planar chiral target compounds plays a crucial role in the molecular interaction with PVY‐CP, enhancing the activity of defense enzymes and affecting chlorophyll content. The current study has provided significant insights into the roles played by planar chiralities in plant protection against viruses. This paves the way for the development of novel green pesticides bearing planar chiralities with excellent optical purities.This article is protected by copyright. All rights reserved.

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Thiazole as an Indispensable Scaffold in Anti‐Leukemic Agents: A Semicentennial Review

Sharma,

Das,

Jadhav

et al. 2024

ChemistrySelect

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Leukemia affects the body‘s blood‐forming tissues, especially the bone marrow and lymphatic system. Leukemia incidence varies between communities and between pathological kinds. Many treatment modalities exist for leukemia, such as chemotherapy, targeted therapy, radiation therapy, bone marrow transplantation, immunotherapy, and the engineering of immune cells to fight leukemia. Leukemia might be treated with a variety of pharmaceuticals, the most popular of which are imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), obinutuzumab (Gazyva), venetoclax (Venclexta), and so on. Thiazole is one of the scaffolds that are actively explored in leukemia. Derivatives having the thiazole nucleus have been surfacing as potent candidates in the treatment of leukemia for quite sometime now, but a consolidated report accumulating all these ventures is absent. Numerous naturally occurring substances, including flavones, alkaloids, anabolic steroids, and vitamin B1 (thiamine), include the basic thiazole molecule. Thiazole derivatives have been researched for their possible therapeutic effects in the treatment of leukemia. Thus, this review comprising reports regarding the effect of different thiazole‐based species in leukemia is a timely effort to the best of our knowledge. This review covers the chronological development of antileukemic thiazole‐based molecules, their synthesis, biological activity, and structure–activity relationships.

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New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies

Cited by 14 publications

References 49 publications

Synthesis of New Planar-Chiral Linked [2.2]Paracyclophanes-N-([2.2]-Paracyclophanylcarbamoyl)-4-([2.2]Paracyclophanylcarboxamide, [2.2]Paracyclophanyl-Substituted Triazolthiones and -Substituted Oxadiazoles

Synthesis of New Planar-Chiral Linked [2.2]Paracyclophanes-N-([2.2]-Paracyclophanylcarbamoyl)-4-([2.2]Paracyclophanylcarboxamide, [2.2]Paracyclophanyl-Substituted Triazolthiones and -Substituted Oxadiazoles

Design, synthesis and Anti‐PVY activity of planar chiral thiourea derivatives incorporated with [2.2]Paracyclophane

Thiazole as an Indispensable Scaffold in Anti‐Leukemic Agents: A Semicentennial Review

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