Click chemistry-assisted synthesis of novel aminonaphthoquinone-1,2,3-triazole hybrids and investigation of their cytotoxicity and cancer cell cycle alterations

Gholampour, Maryam; Ranjbar, Sara; Edraki, Najmeh; Mohabbati, Maryam; Firuzi, Omidreza; Khoshneviszadeh, Mahsima

doi:10.1016/j.bioorg.2019.102967

Cited by 61 publications

(34 citation statements)

References 39 publications

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“…Aminonaphthoquinone conjugates 13 bearing a 1,2,3-triazole linker were synthesized and the conjugates evaluated for their cytotoxicity activity against three human cancer cell lines, namely MCF-7, MOLT-4, and HT-29 [64]. The hybrid with a 4-trifluoromethyl group substituent on the benzyl moiety (compound 13a) displayed excellent activity with an IC 50 glucosidase with two hydrogen-bonding interactions between the NH of the imidazole moiety and Thr307, as well as the nitrogen of 1,2,3-triazole ring and Arg312.…”

Section: Molecules 2020 25 X For Peer Review 14 Of 44mentioning

confidence: 99%

“…Furthermore, two hydrophobic interactions were notable between the 3,5-dimethylbenzyl moiety and the Phe300 and Arg439 residues. Aminonaphthoquinone conjugates 13 bearing a 1,2,3-triazole linker were synthesized and the conjugates evaluated for their cytotoxicity activity against three human cancer cell lines, namely MCF-7, MOLT-4, and HT-29 [64]. The hybrid with a 4-trifluoromethyl group substituent on the benzyl moiety (compound 13a) displayed excellent activity with an IC50 value of 10.4 M against the breast cancer (MCF-7) cell line, as compared to cisplatin (IC50 = 8.8 M) as a reference drug ( Figure 15).…”

Section: Molecules 2020 25 X For Peer Review 14 Of 44mentioning

confidence: 99%

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A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

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Section: Molecules 2020 25 X For Peer Review 14 Of 44mentioning

confidence: 99%

Section: Molecules 2020 25 X For Peer Review 14 Of 44mentioning

confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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“…Flow cytometric analysis revealed that compound 49 arrested the cell cycle at the G0/G1 phase. 88 Compound 50 consisting of three uoro groups showed excellent anticancer activity against HepG2 cells with IC 50 value of 0.0267 mmol mL À1 . 89 The formation of new organoplatinum complexes with triazole rings was examined for their cytotoxic effects on selected cancer (MG-63 and MDA-MB-231) and normal (HDF) cells, and the results were compared with that of cisplatin.…”

Section: Introductionmentioning

confidence: 99%

CuAAC-ensembled 1,2,3-triazole-linked isosteres as pharmacophores in drug discovery: review

et al. 2020

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“…The observed results demonstrated that there was a high toxic effect on BZNQ on HC and HR cells, there were significant differences in cellular apoptosis and ROS levels between HC and HR cells. This is closely associated with the 5,8-dimethoxynaphthalene-1,4-dione core and benzyl group of BZNQ as these subunits may serve an important role in the increase of intracellular ROS levels and cytotoxicity (56). The current study speculates that BZNQ promoted the apoptosis of Ras mutant cell lines by inhibiting the expression of Ras proteins and increasing the level of ROS in H-RasG 12V transfected cells.…”

Section: Discussionmentioning

confidence: 55%

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

Shen

Sun

et al. 2020

Exp Ther Med

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The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-Ras G12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-Ras G12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and β-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.

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Click chemistry-assisted synthesis of novel aminonaphthoquinone-1,2,3-triazole hybrids and investigation of their cytotoxicity and cancer cell cycle alterations

Cited by 61 publications

References 39 publications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

CuAAC-ensembled 1,2,3-triazole-linked isosteres as pharmacophores in drug discovery: review

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

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