452095-59-9

Upstream product

• 66074-00-8 3,4-bis(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide 
• 109-76-2 Trimethylenediamine 
• 156-87-6 propan-1-ol-3-amine 

Downstream Products

• 1245575-26-1 3-(phenylsulfonyl)-4-(3-(2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)benzamido)propoxy)-1,2,5-oxadiazole-2-oxide 

Relevant academic research and scientific papers

Discovery of β-carboline-(phenylsulfonyl)furoxan hybrids as potential anti-breast cancer agents

The cytotoxicity properties of the β-carboline alkaloids have been broadly investigated. However, the potential application of β-carbolines was hindered due to the moderate activity in cancer. In the present study, thirty β-carboline-(phenylsulfonyl)furoxan hybrids (11a–j, 12a–j and 13a–j) were designed and synthesized through esterification and amidation reaction strategy, and their inhibitory activities against the human breast cancer cell lines MCF-7 and MDA-MB-231 were evaluated by CCK-8 assay. Biological evaluation presented that the most promising amide derivative 13h, substituted with p-methoxyphenyl group at position 1, generated high concentration of NO and evidently depressed the MCF-7 (IC50 = 0.89 μM) and MDA-MB-231 (IC50 = 0.62 μM) cells proliferation. Particularly, the wound healing and transwell assays demonstrated that 13h significantly inhibited the migration and invasion of MDA-MB-231cells. Furthermore, the preliminary mechanisms studies indicated that 13h induced G2/M phase arrest and apoptosis possibly causing by ROS accumulation and ROS-mediated DNA damage. Based on these considerations, 13h may be a promising antimetastatic agent for breast cancer, which is noteworthy for further exploration.

Nitric oxide-donating and reactive oxygen species-responsive prochelators based on 8-hydroxyquinoline as anticancer agents

Metal ion chelators based on 8-hydroxyquinoline (8-HQ) have been widely explored for the treatment of many diseases. When aimed at being developed into potent anticancer agent, a largely unmet issue is how to avoid nonspecific chelation of metal ions by 8

Antiproliferative chromone derivatives induce K562 cell death through endogenous and exogenous pathways

A series of furoxan derivatives of chromone were prepared. The antiproliferative activities were tested against five cancer cell lines HepG2, MCF-7, HCT-116, B16, and K562, and two normal human cell lines L-02 and PBMCs. Among them, compound 15a exhibited the most potent antiproliferative activity. It was also found 15a produced more than 8 μM of NO at the peak time of 45 min by Griess assay. Generally, antiproliferative activity is positively related to NO release to some extent. Further in-depth studies on apoptosis-related mechanisms showed that 15a caused S-phase cell cycle arrest in a concentration-dependent manner and induced apoptosis significantly through mitochondria-related pathways. Human apoptosis protein array assay also demonstrated 15a increased the expression levels of pro-apoptotic Bax, Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly up-regulated. In balance, 15a induced K562 cells death through both endogenous and exogenous pathways.

NO donor compounds, compositions, preparation method and application thereof

The object of the present invention is to provide NO donor compounds, compositions, a preparation method and application thereof. The compounds and the compositions show high anticancer activity in in-vitro anticancer activity tests, and have inhibitory a

Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives

To get chelidonine derivatives with enhanced antiproliferative activity and selectivity, a series of nitric oxide donating derivatives (10a-f and 11a-j) were designed, synthesized and biologically evaluated. Compared with chelidonine, these compounds exhibited lower IC50 values against human hepatoma cells HepG2, breast cancer cells MCF-7, colon cancer cells HCT-116, as well as leukemia cells K562. Compound 11j displayed the strongest antiproliferative activity with IC50 values of 3.91, 6.90, 4.36 and 1.12 μM against the above four cells, respectively. Nevertheless, it showed an IC50 value >40 μM against human peripheral blood mononuclear cells (PBMCs), which demonstrated high selectivity between normal and cancer blood cells. In further mechanism studies, 11j showed the capability to induce K562 cells apoptosis, S phase cell cycle arrest and mitochondrial membrane potential disorder. Besides, 11j was found to be effective in promoting the expression of proapoptotic protein Bad and suppressing the expression of anti-apoptotic proteins Bcl-xL, catalase, survivin, claspin and clusterin.

Synthesis of cucurbitacin B derivatives as potential anti-hepatocellular carcinoma agents

Cucurbitacin B shows potent activity against tumor cells, but its high toxicity limits its application in the clinic. A series of cucurbitacin B derivatives was synthesized and evaluated for their anti-hepatocellular carcinoma (HCC) activities against the HepG-2 cell line. These compounds were also tested for their toxicity against the L-O2 normal cell line. The compound with the most potential, 10b, exhibited potent activity against the HepG-2 cell line with an IC50 value of 0.63 μM. Moreover, compound 10b showed the highest TI value (4.71), which is a 14.7-fold improvement compared to its parent compound cucurbitacin B. A preliminary molecular mechanism study of 10b indicated that 10b could inhibit P-STAT3 to induce the activation of mitochondrial apoptotic pathways. An in vivo acute toxicity study indicated that the compound 10b has preferable safety and tolerability compared with cucurbitacin B. These findings indicate that compound 10b might be considered as a lead compound for exploring effective anti-HCC drugs.

Discovery of novel NO-releasing celastrol derivatives with Hsp90 inhibition and cytotoxic activities

To develop multifunctional drugs, a series of celastrol/NO donor hybrids were designed, synthesized and evaluated. The detection of NO release amounts showed that the more NO of these hybrids released, the more tumor cells were inhibited. 11b, which released the highest level of NO in vitro, exhibited superior potency (IC50 = 0.48 ± 0.06 μM) compared to the other compounds. Further pharmacological studies showed that 11b induced dysregulations of the Hsp90 clients (Akt and Cdk4), apoptosis, and cell cycle arrested at G0/G1 phase against A549 cells. These results suggested that inhibition of Hsp90 and release of NO was synergistic in cancer cells. Overall, the NO-releasing capacity and the inhibition of Hsp90 pathway signaling might explain the potent anti-proliferative activities of these compounds.

Quinoline quinine derivative as well as preparation method and application

The invention discloses a quinoline quinine derivative or pharmaceutically acceptable salt, which is of a structure shown in a general formula Ia or Ib shown in the specification. By combination of structural characteristics, structure-function relationships and pharmacophore characteristics of quinoline quinine and furazan nitric acid, on the basis of a quinoline quinine structure, a furazan nitric acid NO donor is introduced; alcohol amines with different lengths are used as connection chains, so that a novel quinoline quinine derivative with NQO1 inhibition activity is designed and synthesized. Research results show that the compound disclosed by the invention has a strong inhibition effect on proliferation of various cells, and can obviously induce ROS expression of tumor cells to synergistically promote apoptosis or necrosis of the tumors.

Design, synthesis and biological evaluation of novel furoxan-based coumarin derivatives as antitumor agents

In order to find new anticancer drugs, a series of novel furoxan-based coumarin derivatives (10a–k) were synthesized and evaluated for their antiproliferative activities in vitro. All compounds displayed more potent inhibition on human cervical cancer HeLa cell proliferation than coumarin-3-carboxylic acid, and compounds 10b, 10c, 10f, 10h, and 10i with IC50 values ranging from 0.88 to 5.95 μM were even stronger than doxorubicin (IC50 = 10.21 μM). The further study showed that compound 10i exerted the highest antiproliferative activity (IC50 = 0.60 μM) against human breast cancer MCF-7 cells, and compound 10f had broader spectrum antiproliferative activity against five cancer cells with IC50 values in the low micromolar range of 1.86–9.85 μM. More interestingly, compound 10f had little effect on normal intestinal epithelial CCD841 cells. Our findings suggest that these novel furoxan-based coumarin derivatives may provide a new framework for the discovery of novel antitumor agents for the intervention of human carcinoma cells.

Scutellarin derivatives as apoptosis inducers: Design, synthesis and biological evaluation

To explore novel antitumor agents with high efficiency and low toxicity, a series of NO-donating scutellarin derivatives (14–17) were synthesized and the antiproliferative activities against MCF-7, HCT-116, PC-3 and HepG2 cancer cell lines were assessed. Among them, compound 14b was the strongest with IC50 values of 2.96?μM, 7.25?μM, 0.09?μM and 0.50?μM, respectively, and displayed low toxicity against normal human liver L-O2 cells with an IC50 of 47.96?μM, showing good selectivity between normal and malignant liver cells. Moreover, NO releasing ability of the derivatives has been studied. Mechanism studies of the most promising compounds 14b and 15a were carried out. The results indicated that 14b and 15a could induce apoptosis, cell cycle arrest at the S phase and led to mitochondrial dysfunction in the HepG2 and PC-3?cell lines, respectively. Furthermore, Human Apoptosis Protein Array kit assay demonstrated that 14b could induce apoptosis through down-regulating the levels of procaspase-3 and inhibiting the expression of survivin, c-IAP1, HSP27, HSP60, HSP70, HO-1/HMOX1/HSP32 and HO-2/HMOX2 in HepG2 cell line. These results guaranteed compound 14b to be a drug candidate against liver cancer for further investigation.