Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

doi:10.1016/j.molstruc.2016.04.058

Cited by 21 publications

(11 citation statements)

References 33 publications

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“…We have earlier demonstrated that N-myristoyltransferase (NMT) and secreted aspartic proteinase (SAP) are potential molecular targets for hydrazinylthiazoles. NMT catalyses the reaction of myristate with important fungal cell proteins (Łączkowski et al 2014b , 2016e ). In contrast, SAP is responsible for the adherence of fungal cells to host epithelial cells followed by colonization of the host tissue.…”

Section: Resultsmentioning

confidence: 99%

“…Hydrazinylthiazole moiety seems to be a good scaffold to generate a variety of antibacterial (Karegoudar et al 2008 ; Mohammad et al 2015 ; Zhao et al 2017 ; Łączkowski et al 2016a , 2017 ), antifungal (Łączkowski et al 2016b ; Carradori et al 2013 ; Chimenti et al 2007 ), anti- Trypanosoma cruzi (de Oliveira Filho et al 2017 ), and anticancer (Łączkowski et al 2016c ; Łączkowski et al 2014a ) drugs. Our earlier studies have shown that incorporation of cyclopentylmethylene and tetrahydro-2 H -thiopyran-4-yl fragments with hydrazinylthiazole moiety was a successful strategy to receive significant anticonvulsant activity in mouse models of seizures (Łączkowski et al 2016d ) and high antifungal activity against clinical isolates of Candida spp.…”

Section: Introductionmentioning

confidence: 99%

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Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti-Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study

et al. 2018

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Synthesis and investigation of antifungal, anticonvulsant and anti-Toxoplasma gondii activities of ten novel (2-(cyclopropylmethylidene)hydrazinyl)thiazole 3a–3j are presented. Among the derivatives, compounds 3a–3d and 3f–3j possess very high activity against Candida spp. ATCC with MIC = 0.015–7.81 µg/ml. Compounds 3a–3d and 3f–3j possess also very high activity towards most of strains of Candida spp. isolated from clinical materials with MIC = 0.015–7.81 µg/ml. The activity of these compounds is similar and even higher than the activity of nystatin used as positive control. Additionally, compounds 3c and 3e showed interesting anticonvulsant activities in the MES test, whereas compounds 3f and 3i demonstrated the anticonvulsant activity in PTZ-induced seizures. Noteworthy, none of these compounds impaired animals’ motor skills in the rotarod test. Moreover, thiazoles 3a, 3h, and 3j showed significant anti-Toxoplasma gondii activity, with IC50 values 31–52 times lower than those observed for sulfadiazine. The results of the cytotoxicity evaluation, anti-Candida spp. and anti-Toxoplasma gondii activity studies showed that Candida spp. and Toxoplasma gondii growth was inhibited at non-cytotoxic concentrations for the mouse L929 fibroblast and the African green monkey kidney (VERO) cells. Molecular docking studies indicated secreted aspartic proteinase (SAP) as possible antifungal target.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti-Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study

et al. 2018

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“…Nitrogen mustards have been used for treatment of cancer, and several pharmaceutical derivatives of nitrogen mustards were developed as cancer therapeutic agents . The carrier part of nitrogen mustards could be substituted with an aromatic substituent, which will stabilize the lone pair of electrons through resonance.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and cytotoxicity of pentacyclic triterpenes‐aniline nitrogen mustard derivatives

Liu

Tian

et al. 2019

J Chinese Chemical Soc

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To discover novel nitrogen mustards, the reported mustard pharmacophore was combined with natural pentacyclic triterpenes, which are characterized with pharmacological and structural diversity. Thus, six conjugates were synthesized with 1,2,3-triazole linking N,N-bis (2-chloroethyl)-1,4-phenylenediamine and oleanolic acid, ursolic acid, or glycyrrhetinic acid, and their biological activity was evaluated against tumor cell lines HeLa, BGC-823, BEL-7404, and NCI-H460 using the MTT assay. As a result, these conjugates showed some selective cytotoxicity to NCI-H460, though all their activity potency was moderate or weak in the four cell lines. K E Y W O R D S N,N-bis (2-chloroethyl)-1,4-phenylenediamine, nitrogen mustards, pentacyclic triterpenes Chun-Mei Liu and Xiao-Yan Tian contributed equally to this study.

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“…Thiazole is an important class of heterocycle which is present in many natural and synthetically available products with diverse pharmacological significance . Thiazoles can be illustrated by a large number of drugs in the market such as the Ritonavir (antiretroviral drug), Sulfathiazole (antibacterial drug) and Tiazofurin (antineoplastic drug) Figure .…”

Section: Introductionmentioning

confidence: 99%

Microwave‐Expedited Green Synthesis, Photophysical, Computational Studies of Coumarin‐3‐yl‐thiazol‐3‐yl‐1,2,4‐triazolin‐3‐ones and Their Anticancer Activity

et al. 2018

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Mild and efficient synthesis of 5‐methyl‐4‐[(2Z)‐4‐(2‐oxo‐2H‐chromen‐3‐yl)‐2‐(4‐arylimino)thiazol‐3(2H)‐yl]‐2‐(4‐aryl)‐2H‐1,2,4‐triazol‐3(4H)‐ones 7(h–s) has been developed using microwave assisted multicomponent route. The molecular structures of these novel compounds were characterized and the photophysical and thermal properties were investigated elaborately using absorption, fluorescence, fluorescence decay lifetimes and thermo gravimetric analysis. Solvatochromism was studied as a function of polarity of the solvents. The ground and excited states of electronic geometric optimizations were computed using density functional theory (DFT and TD‐DFT). The orientation of atomic orbitals and their energies were supported by HOMO‐LUMO calculations. Electrostatic potential (ESP) maps indicated the electron density predicting the reactive sites. Compounds 7(h–s) were docked into the epidermal growth factor receptor (EGFR) tyrosine kinase domain which formed a stable complex with good C‐score values. The title compounds were evaluated for their anticancer activity against A549, MDA‐MBA‐231, HeLa and K562 cancer cell lines which showed sensitivity against most of the tested compounds.

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Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

Cited by 21 publications

References 33 publications

Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti-Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study

Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti-Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study

Synthesis and cytotoxicity of pentacyclic triterpenes‐aniline nitrogen mustard derivatives

Microwave‐Expedited Green Synthesis, Photophysical, Computational Studies of Coumarin‐3‐yl‐thiazol‐3‐yl‐1,2,4‐triazolin‐3‐ones and Their Anticancer Activity

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