Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways

Wang, Jiafeng; Wu, Jiale; Han, Yinglong; Zhang, Jie; Lin, Yu; Wang, Haijun; Wang, Jing; Liu, Jicheng; Bu, Ming

doi:10.3390/molecules26216356

Cited by 5 publications

(2 citation statements)

References 65 publications

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“…Betulin ( Figure 1 ), pentacyclic lupane-structure triterpenoid which occurs abundantly in the birch bark, is one such compound since it has been shown to inhibit growth and migration as well as induce apoptosis of various types of cancer cells. Moreover, betulin can been utilized as a precursor compound for the synthesis of novel derivatives with improved pharmacological properties and potential use in cancer treatment [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

New Betulin Derivatives with Nitrogen Heterocyclic Moiety—Synthesis and Anticancer Activity In Vitro

et al. 2022

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As part of the search for new medicinal substances with potential application in oncology, the synthesis of new compounds combining the betulin molecule and the indole system was carried out. The structure of the ester derivatives obtained in the Steglich reaction was confirmed by spectroscopic methods (1H and 13C NMR, HR-MS). The obtained new 3-indolyl betulin derivatives were evaluated for anticancer activity against several human cancer cell lines (melanomas, breast cancers, colorectal adenocarcinomas, lung cancer) as well as normal human fibroblasts. The significant reduction in MCF-7 cells viability for 28-hydroxy-(lup-20(29)-ene)-3-yl 2-(1H-indol-3-yl)acetate was observed at a concentration of 10 µg/mL (17 µM). In addition, cytometric analysis showed that this compound strongly reduces the proliferation rate of breast cancer cells. For this, the derivative showing the promising cytotoxic effect on MCF-7 breast cancer cells, the pharmacokinetic profile prediction was performed using in silico methods. Based on the results obtained in the study, it can be concluded that indole-functionalized triterpene EB367 is a promising starting point for further research in the field of breast cancer therapy or the synthesis of new derivatives.

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Section: Introductionmentioning

confidence: 99%

New Betulin Derivatives with Nitrogen Heterocyclic Moiety—Synthesis and Anticancer Activity In Vitro

et al. 2022

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“…Covalently bonded networks of POPs are utilized in various biomedical applications because of their cell penetration compatibility, cell viability, and large-scale synthesis facilities [ 26 , 27 , 28 ]. Anticancer activity studies have been carried out on a colorectal carcinoma cell line (HCT 116), where these porous nanomaterials act as cell destroyer or drug delivery systems [ 29 , 30 , 31 ]. Functionalized POP materials having small particle sizes mean they are effective for target-specific cell death.…”

Section: Introductionmentioning

confidence: 99%

N-Rich, Polyphenolic Porous Organic Polymer and Its In Vitro Anticancer Activity on Colorectal Cancer

et al. 2022

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N-rich organic materials bearing polyphenolic moieties in their building networks and nanoscale porosities are very demanding in the context of designing efficient biomaterials or drug carriers for the cancer treatment. Here, we report the synthesis of a new triazine-based secondary-amine- and imine-linked polyphenolic porous organic polymer material TrzTFPPOP and explored its potential for in vitro anticancer activity on the human colorectal carcinoma (HCT 116) cell line. This functionalized (-OH, -NH-, -C=N-) organic material displayed an exceptionally high BET surface area of 2140 m2 g−1 along with hierarchical porosity (micropores and mesopores), and it induced apoptotic changes leading to high efficiency in colon cancer cell destruction via p53-regulated DNA damage pathway. The IC30, IC50, and IC70 values obtained from the MTT assay are 1.24, 3.25, and 5.25 μg/mL, respectively.

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Novel Thiosemicarbazone Derivatives from Furan-2-Carbaldehyde: Synthesis, Characterization, Crystal Structures, and Antibacterial, Antifungal, Antioxidant, and Antitumor Activities

Hernández,

Carrasco,

Vaisberg

et al. 2023

Journal of Chemistry

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Ten new thiosemicarbazone derivatives, furan-2-carbaldehyde thiosemicarbazone (1), 3-methyl-furan-2-carbaldehyde thiosemicarbazone (2), 5-hydroxymethyl-furan-2-carbaldehyde thiosemicarbazone (3), 5-trifluoromethyl-furan-2-carbaldehyde thiosemicarbazone (4), 5-nitro-furan-2-carbaldehyde thiosemicarbazone (5), 5-phenyl-furan-2-carbaldehyde thiosemicarbazone (6), 5-(2-fluorophenyl)-furan-2-carbaldehyde thiosemicarbazone (7), 5-(4-methoxyphenyl)-furan-2-carbaldehyde thiosemicarbazone (8), 5-(1-naphthyl)-furan-2-carbaldehyde thiosemicarbazone (9), and 5-(1H-Pyrazol-5-yl)-furan-2-carbaldehyde thiosemicarbazone (10) were synthesized by condensing thiosemicarbazide with the respective furan-2-carbaldehyde in methanol. The prepared compounds were characterized by spectroscopic studies (FT-IR and NMR) and electrospray mass spectrometry. The molecular structures of 2, 6, 7, and 8 have also been determined by X-ray crystallography. Compounds 2, 6, and 7 crystallize in the E conformation about the N1-C6, N1-C11, and N1-C11 bonds, respectively, while 8 adopts the Z conformation about the N1-C12 bond with the presence of an intramolecular N2-H…O2 hydrogen bond. All prepared thiosemicarbazone derivatives were evaluated for their in vitro antibacterial, antifungal, and antitumor activities against Staphylococcus aureus strains, Candida albicans/Candida tropicalis fungi, and seven human tumor cell lines (HuTu80, H460, DU145, M-14, HT-29, MCF-7, and LNCaP), respectively. The antioxidant activity was also studied by the DPPH assay. Compound 5 exhibited significant antibacterial activity against Staphylococcus aureus ATCC700699 (MIC = 1 μg/mL) compared to the nitrofurantoin and gentamicin reference drugs (MIC = 1–25 and 10->100 μg/mL, respectively). Compound 4 was ten times less active than amphotericin B (MIC = 5 μg/mL) against Candida albicans (ATCC90028 and ATCC10231), while 1 exhibited a moderate effect of scavenging of DPPH radical (IC50 = 40.9 μg/mL) in comparison to ascorbic acid reference compound (IC50 = 22.0 μg/mL). Among all the studied thiosemicarbazones, 5 showed a higher cytotoxic activity (IC50 = 13.36–27.73 μΜ) in relation to the other tested compounds (IC50 = 34.84—>372.34 μΜ) against all tested cell lines, except the LNCaP cell line, exhibiting its highest antiproliferative activity (IC50 = 13.36 μΜ) on the HuTu80 cell line. Besides, 8 and 9 exhibited high antitumor activity (IC50 = 13.31 and 7.69 μΜ, respectively) against the LNCaP cells.

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Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways

Cited by 5 publications

References 65 publications

New Betulin Derivatives with Nitrogen Heterocyclic Moiety—Synthesis and Anticancer Activity In Vitro

New Betulin Derivatives with Nitrogen Heterocyclic Moiety—Synthesis and Anticancer Activity In Vitro

N-Rich, Polyphenolic Porous Organic Polymer and Its In Vitro Anticancer Activity on Colorectal Cancer

Novel Thiosemicarbazone Derivatives from Furan-2-Carbaldehyde: Synthesis, Characterization, Crystal Structures, and Antibacterial, Antifungal, Antioxidant, and Antitumor Activities

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