New IN/I-Adducts of Thiadiazole and Thiazoline with Levoglucosenone and Evaluation of Their Significant Cytotoxic Activity

The anticancer effects reported in several heterocyclic derivatives of thiadiazole and thiazoline prompted us to construct functionalized new carbohydrate heterocycle entities and investigate their potential anticancer effects on several cancer cells. Here, we show that two novel heterocyclic moieti...

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Veröffentlicht in:Cancers 2024-01, Vol.16 (1)
Hauptverfasser: Poplawski, Tomasz, Galita, Grzegorz, Sarnik, Joanna, Macieja, Anna, Bielski, Roman, Mencer, Donald E, Witczak, Zbigniew J
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container_issue 1
container_start_page
container_title Cancers
container_volume 16
creator Poplawski, Tomasz
Galita, Grzegorz
Sarnik, Joanna
Macieja, Anna
Bielski, Roman
Mencer, Donald E
Witczak, Zbigniew J
description The anticancer effects reported in several heterocyclic derivatives of thiadiazole and thiazoline prompted us to construct functionalized new carbohydrate heterocycle entities and investigate their potential anticancer effects on several cancer cells. Here, we show that two novel heterocyclic moieties linked to functionalized carbohydrate with an anhydro scaffold skeleton caused the death of the investigated cancer cells. Interestingly, both N-adducts augmented the cytostatic effect on several cancer cell lines with totally different mechanisms of action. The thiazoline derivative responds via apoptosis through caspase activation and the thiadiazole derivative responds through oxidative stress, DNA damage, and necrosis at the micromolecular level. The conjugate N-adducts of thio-1,3,4-diazole and 2-thiazoline with levoglucosenone were synthesized via a stereoselective, base-catalyzed conjugate N-Michael addition to levoglucosenone at C-4. Structural assignments were established using 1H and 13C NMR analysis, and X-ray single-crystal analysis for one of the compounds. The biological properties of the novel compounds were tested on a cell model. Cytotoxicity was analyzed via colorimetric assay. Two distinct types of cell death, apoptosis and necrosis, were analyzed by determining the phosphatidylserine levels from the outer leaflet of the plasma membrane, caspase activation, and lactate dehydrogenase release. We also evaluated DNA damage using an alkaline comet assay. The level of oxidative stress was measured with a modified comet assay and an H2DCFDA probe. The thio-1,3,4-diazole adduct (FCP23) and the 2-thiazoline adduct (FCP26) exhibit similar cytotoxicity values for cancer cells (ovarian (A2780), breast (MCF-7), cervix (HeLa), colon (LoVo), and brain (MO59J and MO59K)), but their mechanism of action is drastically different. While FCP23 induces oxidative stress, DNA damage, and necrosis, FCP26 induces apoptosis through caspase activation.
doi_str_mv 10.3390/cancers16010216
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Two distinct types of cell death, apoptosis and necrosis, were analyzed by determining the phosphatidylserine levels from the outer leaflet of the plasma membrane, caspase activation, and lactate dehydrogenase release. We also evaluated DNA damage using an alkaline comet assay. The level of oxidative stress was measured with a modified comet assay and an H2DCFDA probe. The thio-1,3,4-diazole adduct (FCP23) and the 2-thiazoline adduct (FCP26) exhibit similar cytotoxicity values for cancer cells (ovarian (A2780), breast (MCF-7), cervix (HeLa), colon (LoVo), and brain (MO59J and MO59K)), but their mechanism of action is drastically different. While FCP23 induces oxidative stress, DNA damage, and necrosis, FCP26 induces apoptosis through caspase activation.</abstract><pub>MDPI AG</pub><doi>10.3390/cancers16010216</doi></addata></record>
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subjects Apoptosis
Cancer
Care and treatment
DNA damage
title New IN/I-Adducts of Thiadiazole and Thiazoline with Levoglucosenone and Evaluation of Their Significant Cytotoxic Activity
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