Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy

Cai, Hao; Huang, Xiaojing; Xu, Shengtao; Shen, Hao; Zhang, Pengfei; Huang, Yue; Jiang, Jieyun; Sun, Yu; Jiang, Bo; Wu, Xiaoming; Yao, Hequan; Xu, Jingyi

doi:10.1016/j.ejmech.2015.11.013

Cited by 84 publications

(41 citation statements)

References 43 publications

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“…Caffeic acid and some of its esters and amides derivatives exhibit a broad spectrum of biological activities including anti-inflammatory [7], antimicrobial [8,9], antioxidant [10], anti-Alzheimer [11], analgesic [12] and anticancer effects [13][14][15]. In addition, some studies have shown that caffeic acid esters have high anti-leishmanial activity [16][17][18][19].…”

Section: Subgenus) As Well As L Mexicana and L Amazonensis (Membermentioning

confidence: 99%

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Otero

García

Palacios

et al. 2017

European Journal of Medicinal Chemistry

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The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eight compounds were active against L. 26 and 28, the remaining compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of the alkyl linker with compound 19, bearing a four-carbon alkyl chain, the most performing hybrid. In general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in the side chain is not decisive for cytotoxicity and anti-protozoal activity.

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Section: Subgenus) As Well As L Mexicana and L Amazonensis (Membermentioning

confidence: 99%

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Otero

García

Palacios

et al. 2017

European Journal of Medicinal Chemistry

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“…The IC50 values were calculated according to the dose-dependent curves. All the tests were repeated in at least three independent experiments [38][39][40].…”

Section: In Vitro Antiproliferative Assaymentioning

confidence: 99%

“…The collected cells were fixed by adding 70% ethanol at 4 o C overnight and incubated for 30 min in PBS containing 100 μL RNase A and 400 μL of propidium iodide. Analysis of the cell DNA content was performed with the system software (Cell Quest, BD Biosciences, USA) [38][39][40].…”

Section: Cell Cycle Analysismentioning

confidence: 99%

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Discovery of novel antitumor nitric oxide-donating β -elemene hybrids through inhibiting the PI3K/Akt pathway

Chen

Wang

et al. 2017

European Journal of Medicinal Chemistry

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A series of novel furoxan-based NO-donating β-elemene hybrids were designed and synthesized to improve the anticancer efficacy of natural β-elemene. The bioassay results indicated that all of the target compounds exhibited significantly improved antiproliferative activities against three cancer cell lines (SGC-7901, HeLa and U87) compared to parent compound β-elemene. Interestingly, these compounds displayed excellent sensitivity to U87 cells with IC50 values ranging from 173 to 2 nM. Moreover, most compounds produced high levels of NO in vitro, and the antitumor activity of 11a in U87 cells was markedly attenuated by an NO scavenger (hemoglobin or carboxy-PTIO). Further mechanism studies revealed that 11a caused the G2 phase arrest of the cell cycle and induced apoptosis of U87 cells by preventing the activation of the PI3K/Akt pathway. Moreover, 11a significantly suppressed the tumor growth in H22 liver cancer xenograft mouse model with a tumor inhibitory ratio (TIR) of 64.8%, which was superior to that of β-elemene (TIR, 49.6%) at the same dose of 60 mg/kg. Together, the remarkable biological profiles of these novel NO-donating β-elemene derivatives may make them promising candidates for the intervention of human cancers.

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“…24 Further, many alkylated 1,2,4-triazoles linked to various aromatic ring systems either through amide or ester linkages have been reported to exhibit significant antitumor activities. [25][26][27] In the last few years, many research groups investigated thienopyrimidine derivatives fused to 1,2,4-triazole moiety as potential cytotoxic agents. [28][29][30] For example, the fusion of a triazole ring to cycloalkylthieno [2,3-d]pyrimidine (VII) showed significant in vitro cytotoxic activity against human colorectal cancer cells (HCT-116) (IC 50 = 2.8 μg/mL) compared to the reference drug Doxorubicin (Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Cytotoxicity of substituted[1]benzothieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidines

Botros¹,

Khalil²,

Kamel³

et al. 2017

ACSi

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A new series of 4-benzyl-6,7,8,9-tetrahydro[1]benzothieno [3,2-e] [1,2,4]triazolo [4,3-a]pyrimidines was synthesized motivated by the widely reported anticancer activity of thieno [2,3-d]pyrimidines and triazolothienopyrimidines. The in vitro cytotoxic activity of some selected compounds was evaluated against two human cell lines: prostate cancer (PC-3) and colon cancer (HCT-116). A preliminary study of the structure-activity relationship of the target compounds was discussed. Most of the synthesized compounds showed remarkable activity on the tested cell lines, while compound 16c had the highest potency against the PC-3 cell line with an IC 50 of 5.48 μM compared to Doxorubicin (IC 50 = 7.7 μM), the reference standard used in this study. On the other hand, 6c and 18c were the most active against HCT-116 (IC 50 = 6.12 and 6.56 μM, respectively) relative to IC 50 = 15.82 μM of the standard. Thus, some of the synthesized thienopyrimidine derivatives, specially 6c, 16c and 18c, have the potential to be developed into potent anticancer agents.

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Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy

Cited by 84 publications

References 43 publications

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Discovery of novel antitumor nitric oxide-donating β -elemene hybrids through inhibiting the PI3K/Akt pathway

Synthesis, Characterization and Cytotoxicity of substituted[1]benzothieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidines

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