Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis

Lü, Xiaoyuan; Wang, Zhongchang; Ren, Shen-Zhen; Shen, Fa-Qian; Man, Ruo‐Jun; Zhu, Hai‐Liang

doi:10.1016/j.bmcl.2016.06.037

Cited by 74 publications

(37 citation statements)

References 29 publications

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“…One of the consequences on intracellular COX inhibition is decreased production of prostaglandin E2 (PGE 2 ) 36 . To confirm that the strong COX-2 inhibitory effects of our compounds is maintained in cells, we treated HeLa cells with compounds 2b , 11b , celecoxib and indomethacin for 24 hours then measured the level of PGE 2 produced in the cell culture supernatant.…”

Section: Resultsmentioning

confidence: 99%

“…To confirm that the strong COX-2 inhibitory effects of our compounds is maintained in cells, we treated HeLa cells with compounds 2b , 11b , celecoxib and indomethacin for 24 hours then measured the level of PGE 2 produced in the cell culture supernatant. HeLa cell line was chosen for this study because it has been previously used for a similar study 36 (see Table S1 supporting information for the IC 50 of these compounds in HeLa cells). As shown in Figure 7, both compounds 2b and 11b significantly inhibited PGE 2 production, confirming that these NSAID-HDACi conjugates possess intracellular COX-2 inhibitory activities as well.…”

Section: Resultsmentioning

confidence: 99%

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Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase

Raji

Yadudu

Janeira

et al. 2017

Bioorganic & Medicinal Chemistry

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We herein disclose a series of compounds with potent inhibitory activities towards histone deacetylases (HDAC) and cyclooxygenases (COX). These compounds potently inhibited the growth of cancer cell lines consistent with their anti-COX and anti-HDAC activities. While compound 2b showed comparable level of COX-2 selectivity as celecoxib, compound 11b outperformed indomethacin in terms of selectivity towards COX-2 relative to COX-1. An important observation with our lead compounds (2b, 8, 11b, and 17b) is their enhanced cytotoxicity towards androgen dependent prostate cancer cell line (LNCaP) relative to androgen independent prostate cancer cell line (DU-145). Interestingly, compounds 2b and 17b arrested the cell cycle progression of LNCaP in the S-phase, while compound 8 showed a G0/G1 arrest, similar to SAHA. Relative to SAHA, these compounds displayed tumor-selective cytotoxicity as they have low anti-proliferative activity towards healthy cells (VERO); an attribute that makes them attractive candidates for drug development.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase

Raji

Yadudu

Janeira

et al. 2017

Bioorganic & Medicinal Chemistry

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“…Few radiofrequency ablation (RFA) reports focused solely on early-stage primary lung cancer, although a recently published phase II trial demonstrated local relapse in 19 of 51 high-risk patients with stage T1a NSCLC after a single RFA procedure. 26 Two-year local control was 63.7% and 56.1% for lesions , and . 2 cm, respectively, with an 11.8% rate of severe toxicity at 90 days.…”

Section: Ablative Techniquesmentioning

confidence: 95%

Management of Patients With Stage I Lung Cancer

Wallen

2017

JOP

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The treatment of stage I non-small-cell lung cancer has advanced markedly over the past century. The transition from therapeutic nihilism with ensured mortality to radical surgery with pneumonectomy to rational oncologic-based resection has resulted in dramatically improved outcomes and reduced morbidity. The superiority of anatomic resection with lobectomy over sublobar resection for fit patients with stage I disease, where more than one half of all patients should expect to be cured, is backed by level 1 evidence. Minimally invasive approaches have further decreased morbidity and mortality, and prospective trials continue to assess whether sublobar resection is appropriate in more select circumstances for tumors < 2 cm. Interest in studying the patient at high risk for complications after lobectomy has been spurred by recent advances in surgical, radiotherapy, and ablative treatment options. In particular, provocative results with stereotactic body radiotherapy have led to rapid adoption in clinical practice with a resultant decrease in the number of untreated patients. A comparison of outcomes across studies of competing modalities remains challenging given the potential impact of selection bias in single-arm trials, and attempts to conduct randomized studies have been largely unsuccessful. Given the uncertainty in defining optimal therapy, patients are best served by a multidisciplinary team of thoracic surgeons, radiation oncologists, pulmonologists, and chest and interventional radiologists to ensure that they receive the evaluation and treatment best suited not only to their tumor and medical challenges but also to their concerns, fears, and values.

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“…[1 -3] Besides, a series of synthetic coumarin sulfonamides, triazole coumarins, thiazole coumarins, indolyl coumarins, imidazole coumarins, and 4-substituted coumarin derivatives were found to have anti-HIV, antibacterial, antioxidant, inhibiting ACE, antifungal, scavenging of reactive oxygen species (ROS), anti-inflammatory, and anticancer activities. [4][5][6][7][8][9][10][11][12] More importantly, some of them have made their way to clinics including warfarin (anticoagulant), hymecromone (choleretic and antispasmodic), armillarisin A (antibiotic), carbochromen (coronary disease), and cloricromene (antithrombotic and antiplatelet), as shown in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

5‐Phenylcoumarin Derivatives: Design, Synthesis, and Vasodilatory Activity

Wang

Zhang

et al. 2018

Chemistry & Biodiversity

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In continuation of our previous efforts towards the development of coumarin derivatives with potential vasodilatory activity, 5-phenylcoumarin derivatives were designed and synthesized. Target compounds and their precursors exhibited moderately vasodilatory ability with EC at 2.5-49.0 μm. Docking studies also revealed the good binding mode of 7-methoxy-8-[2-(pyrrolidin-1-yl)ethoxy]-5-[2-(trifluoromethyl)phenyl]-2H-chromen-2-one (8c) with the target protein. Moreover, intermediates and the final products exhibited different fluorescent properties due to their substituent effect. These results may provide new ideas for the synthesis and application of 5-substituted coumarins.

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Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis

Cited by 74 publications

References 29 publications

Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase

Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase

Management of Patients With Stage I Lung Cancer

5‐Phenylcoumarin Derivatives: Design, Synthesis, and Vasodilatory Activity

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