Design, synthesis and in vitro cytotoxicity studies of novel β -carbolinium bromides

Reddy, Polimera Obula; Mishra, Shriprada; Tantak, Mukund P.; Nikhil, Kumar; Sadana, Rachna; Shah, Kavita; Kumar, Dalip

doi:10.1016/j.bmcl.2017.02.010

Cited by 12 publications

(6 citation statements)

References 34 publications

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“…All reagents were purchased from commercial suppliers and were dried and purified when necessary. The following intermediates 3a - 3b 29 , 3c - 3e 21 , 3f 30 , 3g 31 , 3h 32 , 4g - 4h 33 were prepared as previously described.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and biological evaluation of novel N⁹-heterobivalent β-carbolines as angiogenesis inhibitors

Guo

Ma²,

Chen³

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of novel N9-heterobivalent β-carbolines has been synthesized. All the novel compounds were tested for their anticancer activity against six tumour cell lines in vitro. Among these molecules, compounds 5b, and 5w exhibited strong cytotoxic activities with IC50 value of lower than 20 μM. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 5b and 5w exhibited that tumour inhibition rate of over 40% in the Sarcoma 180 and Lewis lung cancer animal models. Preliminary structure–activity relationships (SARs) analysis indicated that: (1) C1-methylation and C7-methoxylation were favorable for increased activities; (2) 3-Pyridyl or 2-thienyl group substituent into position-1 of the β-carboline core, and the aryl substituent into another β-carboline ring might be detrimental to cytotoxic effects of this class compounds. Investigation of the preliminary mechanism of action demonstrated that compound 5b had obvious angiogenesis inhibitory effects in the chicken chorioallantoic membrane (CAM) assay.

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Section: Methodsmentioning

confidence: 99%

Synthesis and biological evaluation of novel N⁹-heterobivalent β-carbolines as angiogenesis inhibitors

Guo

Ma²,

Chen³

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Anti-proliferation and apoptosis induction were demonstrated as the main cytotoxic effects. For example, harmine and its analogues have the function of anti-proliferation and apoptosis induction in many cancer cell lines, such as human thyroid cancer TPC1 cells, human colorectal carcinoma SW620 cells and human prostate cancer C4-2 cells [ 21 , 22 , 23 ]. Our previous research found that harmine could induce G2/M cell cycle arrest and apoptosis in the Spodoptera litura SL-1 cell line [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

Zhang

Shu

et al. 2018

IJMS

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Harmine, one of the natural β-carboline alkaloids extracted from Peganum harmala L., exhibits broad spectrum but limited insecticidal ability against many pests. So there is an urgent need to synthesize novel derivatives with high efficiency. In the present study, a new synthetic compound, [1-(2-naphthyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carboline] (ZC-14), showed a strong proliferation inhibition effect against the Spodoptera frugiperda Sf9 cell line in a dose-dependent manner. Simultaneously, apoptosis induced by 7.5 μg/mL ZC-14 was confirmed with physiological and biochemical evidence, including typical apoptosis characteristics with shrinkage, apoptotic bodies, nuclear condensation/fragmentation, a clear DNA ladder, and a series of apoptotic rates. In addition, mitochondria were confirmed to be involved in apoptosis induced by ZC-14 accompanied with the loss of mitochondrial membrane potential (Δψm), the release of cytochrome c from mitochondria into the cytosol and increased expression of cleaved-caspase-3. However, harmine could not induce apoptosis at the same concentration. In summary, these data indicated that compound ZC-14 has a higher cytotoxicity than harmine against Sf9 cells. Besides, it exhibited an anti-proliferative effect in Sf9 cells via inducing apoptosis in which the mitochondrial apoptotic pathway plays a crucial role.

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“…We emphasize that, using these parameters to compare drug efficacy between distinct cell populations (such as cell lines), cells that grow “faster” in culture will be inferred more sensitive than “slower” ones, and therefore these parameters lead to a misinterpretation of the results because of their dependency to the unique growth properties of each cell population. Despite PG partially overcomes this limitation, we provide in the first section of the results a detailed description of the dependency of R , and consequently the IC 50 , to cell proliferation rate because of its frequent usage in current anticancer drug discovery research (as few recent examples (Ben et al, ; Cabrera et al, ; Esposito et al, ; Hamed, Darwish, Herrmann, Abadi, & Engel, ; Indovina et al, ; Koul et al, ; Mathema, Chaijaroenkul, Karbwang, & Na‐Bangchang, ; Menderes et al, ; Mukunthan, Satyan, & Patel, ; Muñoz, Rosso, & Coveñas, ; Potenza et al, ; Ravi, Ramesh, & Pattabhi, ; Rimoldi et al, ; Said, Brouard, Quintana, & Estévez, ; Venkataramana Reddy et al, ; Wehbe et al, ; Zamora et al, ; Zhu et al, )). Subsequently, in the second section of the results, we show that PG is also dependent on the growth properties of the cells, because of their exponential and not linear proliferation in culture.…”

Section: Introductionmentioning

confidence: 99%

A new parameter of growth inhibition for cell proliferation assays

Fiorentino¹,

Bagella²,

Marchesi³

2017

Journal Cellular Physiology

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Cell proliferation assays are performed by four decades to test the anti-proliferative activity of natural products and synthetic compounds in cell cultures. In cancer research, they are widely employed to evaluate drug efficacy in in vitro tumor models, such as established cell lines, primary cultures, and recently developed three-dimensional tumor organoids. In this manuscript, we demonstrated that current employed parameters used by researchers to quantify in vitro growth inhibition, IC and GI , lead to a misinterpretation of results based on the exponential, and not linear, proliferation of the cells in culture. Therefore, we introduce a new parameter for the analysis of growth inhibition in cell proliferation assays, termed relative population doubling capacity, that can be employed to properly quantify the anti-proliferative activity of tested compounds and to compare drug efficacy between distinct cell models.

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Design, synthesis and in vitro cytotoxicity studies of novel β -carbolinium bromides

Cited by 12 publications

References 34 publications

Synthesis and biological evaluation of novel N⁹-heterobivalent β-carbolines as angiogenesis inhibitors

Synthesis and biological evaluation of novel N⁹-heterobivalent β-carbolines as angiogenesis inhibitors

Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

A new parameter of growth inhibition for cell proliferation assays

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Design, synthesis and in vitro cytotoxicity studies of novel β -carbolinium bromides

Cited by 12 publications

References 34 publications

Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors

Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors

Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells

A new parameter of growth inhibition for cell proliferation assays

Contact Info

Product

Resources

About

Synthesis and biological evaluation of novel N⁹-heterobivalent β-carbolines as angiogenesis inhibitors

Synthesis and biological evaluation of novel N⁹-heterobivalent β-carbolines as angiogenesis inhibitors