Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies

Jakovljević, Katarina; Matić, Ivana Z.; Petrović, Nina; Stanojković, Tatjana; Sladić, Dušan; Vujčić, Miroslava; Janović, Barbara; Joksović, Ljubinka; Trifunović, Snežana; Marković, Violeta

doi:10.1039/c8md00316e

Cited by 27 publications

(14 citation statements)

References 62 publications

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“…In addition, 1,3,4-thiadiazole also represents a key heterocyclic motif in medicinal chemistry owing to its high electron-donating ability to form hydrogen bonds or to coordinate metal ions 31 . Some 1,3,4-thiadiazole derivatives have been reported for their considerable anticancer properties 32 , 33 . Molecular hybridisation may be a strategy to enhance activity or selectivity and overcome the side effects associated with the original compound 32 .…”

Section: Introductionmentioning

confidence: 99%

“…Some 1,3,4-thiadiazole derivatives have been reported for their considerable anticancer properties 32 , 33 . Molecular hybridisation may be a strategy to enhance activity or selectivity and overcome the side effects associated with the original compound 32 . Therefore, the introduction of quinoline, oxadiazole, and/or thiadiazole moieties to the molecule of UA may probably afford novel derivatives with promising anticancer activities.…”

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors

Jin

Chen

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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In this article, a series of novel quinoline derivatives of ursolic acid (UA) bearing hydrazide, oxadiazole, or thiadiazole moieties were designed, synthesised, and screened for their in vitro antiproliferative activities against three cancer cell lines (MDA-MB-231, HeLa, and SMMC-7721). A number of compounds showed significant activity against at least one cell line. Among them, compound 4d exhibited the most potent activity against three cancer cell lines with IC 50 values of 0.12 ± 0.01, 0.08 ± 0.01, and 0.34 ± 0.03 lM, respectively. In particular, compound 4d could induce the apoptosis of HeLa cells, arrest cell cycle at the G0/G1 phase, elevate intracellular reactive oxygen species level, and decrease mitochondrial membrane potential. In addition, compound 4d could significantly inhibit MEK1 kinase activity and impede Ras/Raf/ MEK/ERK transduction pathway. Therefore, compound 4d may be a potential anticancer agent and a promising lead worthy of further investigation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors

Jin

Chen

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Reactive oxygen species consist of O 2 – , H 2 O 2 , hydroxyl radical, and ozone ( Yang et al, 2020 ). Being the most stable ROS element, H 2 O 2 can stimulate the production of endogenous ROS and trigger oxidative damage ( Jakovljević et al, 2018 ). Co-incubation of T. gondii mutants with H 2 O 2 is a strategy for determining whether genes are associated with resistance to ROS ( Ding et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide CRISPR/Cas9 Screen Identifies New Genes Critical for Defense Against Oxidant Stress in Toxoplasma gondii

et al. 2021

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Toxoplasma gondii is one of the most widespread apicomplexans and can cause serious infections in humans and animals. Its antioxidant system plays an important role in defending against oxidant stress imposed by the host. Some genes encoding the antioxidant enzymes of T. gondii have been identified; however, critical genes that function in response to reactive oxygen species (ROS) stress are still poorly understood. Here, we performed genome-wide CRISPR/Cas9 loss-of-function screening in the T. gondii RH strain to identify potential genes contributing to the ROS stress response. Under hydrogen peroxide treatment, 30 single guide RNAs targeting high-confidence genes were identified, including some known important antioxidant genes such as catalase and peroxiredoxin PRX3. In addition, several previously uncharacterized genes were identified, among which five hypothetical protein-coding genes, namely, HP1–HP5, were selected for further functional characterization. Targeted deletion of HP1 in T. gondii RH led to significant sensitivity to H2O2, suggesting that HP1 is critical for oxidative stress management. Furthermore, loss of HP1 led to decreased antioxidant capacity, invasion efficiency, and proliferation in vitro. In vivo results also revealed that the survival time of mice infected with the HP1-KO strain was significantly prolonged relative to that of mice infected with the wild-type strain. Altogether, these findings demonstrate that the CRISPR/Cas9 system can be used to identify potential genes critical for oxidative stress management. Furthermore, HP1 may confer protection against oxidative damage and contributes to T. gondii virulence in mice.

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“…The hybrids of 1,3,4-thiadiazole and chalcone containing phenolic moiety are the other example of molecules binding to DNA. These derivatives exerted the strong cytotoxic activity against leukemia HL-60 cells with IC 50 [88].…”

Section: Compounds Interacting With Dnamentioning

confidence: 99%

“…The derivatives most potent in HeLa cells, 5a (( E )- N -(5-(3,4-Dihydroxyphenyl)-1,3,4-thiadiazol-2-yl)-4-(3-oxo-3-phenylprop-1-en-1-yl)benz-amide), 5c (( E )- N -(5-(3,4-Dihydroxyphenyl)-1,3,4-thiadiazol-2-yl)-4-(3-oxo-3-(m-tolyl)prop-1-en-1-yl)benz-amide), 5f (( E )- N -(5-(3,4-Dihydroxyphenyl)-1,3,4-thiadiazol-2-yl)-4-(3-(3-methoxyphenyl)-3-oxoprop-1-en-1-yl)benzamide) and 5 m (( E )- N -(5-(3,4-Dihydroxyphenyl)-1,3,4-thiadiazol-2-yl)-4-(3-oxo-3-(thiophen-2-yl)prop-1-en-1-yl)benzamide), were subjected to further analyses. Treatment with these compounds caused G2/M cell cycle arrest, triggered caspase-dependent apoptosis and induced DNA damage [ 88 ].…”

Section: Derivatives 134-thiadiazolementioning

confidence: 99%

Thiadiazole derivatives as anticancer agents

Szeliga

2020

Pharmacol. Rep

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In spite of substantial progress made toward understanding cancer pathogenesis, this disease remains one of the leading causes of mortality. Thus, there is an urgent need to develop novel, more effective anticancer therapeutics. Thiadiazole ring is a versatile scaffold widely studied in medicinal chemistry. Mesoionic character of this ring allows thiadiazole-containing compounds to cross cellular membrane and interact strongly with biological targets. Consequently, these compounds exert a broad spectrum of biological activities. This review presents the current state of knowledge on thiadiazole derivatives that demonstrate in vitro and/or in vivo efficacy across the cancer models with an emphasis on targets of action. The influence of the substituent on the compounds’ activity is depicted. Furthermore, the results from clinical trials assessing thiadiazole-containing drugs in cancer patients are summarized.

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Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies

Abstract: 1,3,4-Thiadiazole compounds containing catechol moiety and chalcone motif are synthesized and examined for antioxidant activity, cytotoxicity and DNA-binding activity.

Cited by 27 publications

References 62 publications

Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors

Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors

Genome-Wide CRISPR/Cas9 Screen Identifies New Genes Critical for Defense Against Oxidant Stress in Toxoplasma gondii

Thiadiazole derivatives as anticancer agents

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