Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM)

Elkamhawy, Ahmed; Viswanath, Ambily Nath Indu; Pae, Ae Nim; Kim, Hyeon Young; Heo, Jin‐Chul; Park, Woo‐Kyu; Lee, Chong‐Ock; Yang, Heekyoung; Kim, Kang Ho; Nam, Do‐Hyun; Seol, Ho Jun; Cho, Heeyeong; Roh, Eun Joo

doi:10.1016/j.ejmech.2015.08.001

Cited by 21 publications

(8 citation statements)

References 30 publications

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“…The general protocol used for the chemical synthesis, elucidation of the chemical structures, and purity of the synthesized melatonin derivatives are detailed in Supplementary Material, as reported earlier [77][78][79][80].…”

Section: Chemical Reagents Purification and Instrumentationmentioning

confidence: 99%

Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress

et al. 2021

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Monoamine oxidase B (MAO-B) metabolizes dopamine and plays an important role in oxidative stress by altering the redox state of neuronal and glial cells. MAO-B inhibitors are a promising therapeutical approach for Parkinson’s disease (PD). Herein, 24 melatonin analogues (3a–x) were synthesized as novel MAO-B inhibitors with the potential to counteract oxidative stress in neuronal PC12 cells. Structure elucidation, characterization, and purity of the synthesized compounds were performed using 1H-NMR, 13C-NMR, HRMS, and HPLC. At 10 µM, 12 compounds showed >50% MAO-B inhibition. Among them, compounds 3n, 3r, and 3u‒w showed >70% inhibition of MAO-B and IC50 values of 1.41, 0.91, 1.20, 0.66, and 2.41 µM, respectively. When compared with the modest selectivity index of rasagiline (II, a well-known MAO-B inhibitor, SI > 50), compounds 3n, 3r, 3u, and 3v demonstrated better selectivity indices (SI > 71, 109, 83, and 151, respectively). Furthermore, compounds 3n and 3r exhibited safe neurotoxicity profiles in PC12 cells and reversed 6-OHDA- and rotenone-induced neuronal oxidative stress. Both compounds significantly up-regulated the expression of the anti-oxidant enzyme, heme oxygenase (HO)-1. Treatment with Zn(II)-protoporphyrin IX (ZnPP), a selective HO-1 inhibitor, abolished the neuroprotective effects of the tested compounds, suggesting a critical role of HO-1 up-regulation. Both compounds increased the nuclear translocation of Nrf2, which is a key regulator of the antioxidative response. Taken together, these data show that compounds 3n and 3r could be further exploited for their multi-targeted role in oxidative stress-related PD therapy.

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Section: Chemical Reagents Purification and Instrumentationmentioning

confidence: 99%

Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress

et al. 2021

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“…GBM is highly invasive and have very poor prognosis. Unfortunately the life expectancy of the patients is not more than 12-16 months after the diagnosis (20)(21)(22). Furthermore it has been reported that HCMV may promote the GBM pathogenesis and may induce tumor growth and invasion (19,20).…”

Section: Introductionmentioning

confidence: 99%

The concurrent effect of acyclovir and rosemary on glioblastoma cell culture

Özdemir

Göktürk

2019

Cell Mol Biol (Noisy-le-grand)

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Human cytomegalovirus (HCMV) is a beta herpesvirus which large amount of people in world has interacted with. Recent studies indicated that CMV DNA is associated with several cancer types including "Glioblastoma (GBM)" which is the most common and aggressive type of primary brain cancer. In clinical studies it was shown that several antiviral medicines prolonged life span of glioblastoma patients. One of them is Acyclovir (ACV) which is a type of nucleoside analog, used to cure viral infections and might be a potential treatment supplement for Glioblastoma. In this study we aimed to investigate if ACV had cytotoxic effect on glioblastoma cell line U87 MG and also the effect of ACV on healthy cells. Furthermore it was aimed to search the effect of Rosmarinus Officinalis also known as rosemary which is an aromatic, perennial plant concurrent with ACV on glioblastoma and healthy cells.

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“…In addition, they also reported new quinazoline-urea based compounds with potent cytotoxic activities against TMZ-resistant glioblastoma multiforme (GBM) cells, which may be associated with plausible binding modes in translocator protein 18 kDa (TSPO). Overall, these studies proved that novel quinazoline-based compounds are promising candidates for cancer therapy possessing potency and various activity (Elkamhawy et al, 2015b).…”

Section: Introductionmentioning

confidence: 75%

Discovery of a Series of 1,2,3-Triazole-Containing Erlotinib Derivatives With Potent Anti-Tumor Activities Against Non-Small Cell Lung Cancer

Mao

Deng

et al. 2022

Front. Chem.

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are emerging at the vanguard of therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the increasing therapeutic resistance caused by novel mutations or activated bypass pathways has impaired their performance. In this study, we link one of the commercial EGFR-TKIs, Erlotinib, to different azide compounds to synthesize a novel class of 1,2,3-triazole ring-containing Erlotinib derivatives. We discovered that several new compounds show robust antiproliferation activity against diverse NSCLC cells in vitro including PC-9, H460, H1975 and A549. Two of the most potent compounds, e4 and e12 have been found to be more efficient than Erlotinib in all NSCLC cell lines except PC-9. They significantly induce apoptosis and cell cycle arrest in PC-9 and H460 cells. The antitumor efficacy of compound e4 in vivo is close to that of Erlotinib in a PC-9 xenograft mouse model. Most Erlotinib-1,2,3-triazole compounds exhibit moderate to good inhibitory activities toward wild-type EGFR as indicated by enzyme-linked immunosorbent assay (ELISA), and the EGFR phosphorylation was inhibited in H460 and PC-9 cells exposed to e4 or e12. These data suggest that these Erlotinib-1,2,3-triazole compounds are suitable candidates for use against NSCLC and more unknown mechanisms merit further investigation.

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Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM)

Cited by 21 publications

References 30 publications

Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress

Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress

The concurrent effect of acyclovir and rosemary on glioblastoma cell culture

Discovery of a Series of 1,2,3-Triazole-Containing Erlotinib Derivatives With Potent Anti-Tumor Activities Against Non-Small Cell Lung Cancer

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