Synthesis and biological activity of new phthalimides as potential anti-inflammatory agents

Bach, Duc-Hiep; Liu, Jianyu; Kim, Won Kyung; Hong, Ji‐Young; Park, So Hyun; Kim, Donghwa; Qin, Si-ning; Luu, Thi-Thu-Trang; Park, Hyen Joo; Xu, Yongnan; Lee, Sang Kook

doi:10.1016/j.bmc.2017.04.027

Cited by 45 publications

(29 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In some poses, the triazole can make H-bonds to Gln350 or Ser530. In agreement with recent studies on different compounds, 30,31) our results demonstrate the important role of the phthalimide group in the biological effect, and indicate possible routes for future improvement.…”

Section: Pharmacologysupporting

confidence: 92%

Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity

Assis

Silva

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Phthalimido-alkyl-1H-1,2,3-triazole derivatives 3a-d and 4a-d were efficiently synthesized using 1,3-dipolar cycloaddition reaction. Anti-inflammatory activity and toxicity studies were performed. The results demonstrated that all the tested compounds reduced carrageenan-induced paw edema and indicated no lethality for toxicity against Artemia salina and acute toxicity in vivo (LD 50 up to 1 g kg 1). Furthermore, the structure of phthalimide linked to phenyl group proved to be more active than the compounds containing benzothiazole moiety. Structural modifications such as removal of the phthalimide group and subsequent acetylation, to exemplify a non-cyclic amide, demonstrate that the phthalimide and triazole moieties are important for design of potent candidates with anti-inflammatory drug proprieties. Docking into the cyclooxygenase-2 (COX-2) confirms the importance of the phthalimide and triazole groups in the anti-inflammatory activity. The histopathological studies showed that the compounds 3a-d and 4a-d did not cause serious pathological lesions liver or kidneys.

show abstract

Section: Pharmacologysupporting

confidence: 92%

Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity

Assis

Silva

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…RNA extraction and real-time PCR were carried out similarly as described previously. 36 , 43 Gene-specific primers for real-time PCR were synthesized by Bioneer Corporation (Daejeon, Korea): human NNMT sense: 5′-TGTGTGATCTTGAAGGGAACAG-3′, antisense: 5′-CTTGACCGCCTGTCTCAAC-3′; human β-actin sense: 5′-AGCACAATGAAGATCAAGAT-3′, antisense: 5′-TGTAACGCAACTAAGTCATA-3′.…”

Section: Methodsmentioning

confidence: 99%

Targeting Nicotinamide N-Methyltransferase and miR-449a in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer Cells

Bach

Kim

Bae

et al. 2018

Molecular Therapy - Nucleic Acids

Self Cite

View full text Add to dashboard Cite

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used clinically as target therapies for lung cancer patients, but the occurrence of acquired drug resistance limits their efficacy. Nicotinamide N-methyltransferase (NNMT), a cancer-associated metabolic enzyme, is commonly overexpressed in various human tumors. Emerging evidence also suggests a crucial loss of function of microRNAs (miRNAs) in modulating tumor progression in response to standard therapies. However, their precise roles in regulating the development of drug-resistant tumorigenesis are still poorly understood. Herein, we established EGFR-TKI-resistant non-small-cell lung cancer (NSCLC) models and observed a negative correlation between the expression levels of NNMT and miR-449a in tumor cells. Additionally, knockdown of NNMT suppressed p-Akt and tumorigenesis, while re-expression of miR-449a induced phosphatase and tensin homolog (PTEN), and inhibited tumor growth. Furthermore, yuanhuadine, an antitumor agent, significantly upregulated miR-449a levels while critically suppressing NNMT expression. These findings suggest a novel therapeutic approach for overcoming EGFR-TKI resistance to NSCLC treatment.

show abstract

“…Western blot analysis was performed as described previously, using equal amounts of protein from each cell lysate 48, 50, 51, 52. The following antibodies were used: anti-BMP4 (ab39973, Abcam, UK); anti-p53 (DO-1) (sc-126); anti-β-actin (C4) (sc-47778) (Santa Cruz Biotechnology, Santa Cruz, CA, USA); anti-p-Smad1/5 (Ser463/465) (9516); anti-p-p53 (Ser15) (9284) (Cell Signaling Technology, Danvers, MA, USA); and anti-ACSL4 (PA5-27137) (Invitrogen, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Total cell or tumor tissue RNA was extracted with TRI reagent (Invitrogen, Grand Island, NY, USA), and then RT-PCR analysis was carried out as described previously 48, 50. Gene-specific primers for real-time PCR were synthesized by Bioneer (Daejeon, Korea): human ACSL4 sense, 5′-TTCATCTCTTGGACTTTGCTCA-3′; antisense, 5′-TGTACTGTACTGAAGCCCACACTT-3′; human BMP4 sense, 5′-GGGATGTTCTCCAGATGTTCTT-3′; and antisense, 5′-TCCACAGCACTGGTCTTGAG-3′.…”

Section: Methodsmentioning

confidence: 99%

BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells

Bach

Luu

Kim

et al. 2018

Molecular Therapy - Nucleic Acids

Self Cite

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer-associated deaths worldwide. In particular, non-small-cell lung cancer (NSCLC) cells harboring epidermal growth factor receptor (EGFR) mutations are associated with resistance development of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. Recent findings suggest that bone morphogenetic proteins (BMPs) and microRNAs (miRNAs) might act as oncogenes or tumor suppressors in the tumor microenvironment. In this study, for the first time, we identified the potential roles of BMPs and miRNAs involved in EGFR-TKI resistance by analyzing datasets from a pair of parental cells and NSCLC cells with acquired EGFR-TKI resistance. BMP4 was observed to be significantly overexpressed in the EGFR-TKI-resistant cells, and its mechanism of action was strongly associated with the induction of cancer cell energy metabolism through the modulation of Acyl-CoA synthetase long-chain family member 4. In addition, miR-139-5p was observed to be significantly downregulated in the resistant NSCLC cells. The combination of miR-139-5p and yuanhuadine, a naturally derived antitumor agent, synergistically suppressed BMP4 expression in the resistant cells. We further confirmed that LDN-193189, a small molecule BMP receptor 1 inhibitor, effectively inhibited tumor growth in a xenograft nude mouse model implanted with the EFGR-TKI-resistant cells. These findings suggest a novel role of BMP4-mediated tumorigenesis in the progression of acquired drug resistance in EGFR-mutant NSCLC cells.

show abstract

Synthesis and biological activity of new phthalimides as potential anti-inflammatory agents

Cited by 45 publications

References 18 publications

Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity

Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity

Targeting Nicotinamide N-Methyltransferase and miR-449a in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer Cells

BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells

Contact Info

Product

Resources

About