The Synthesis of a Novel Anticancer Compound, N-(3,5 Dimethoxyphenyl) Acridin-9-Amine and Evaluation of Its Toxicity

Ismail, Nur Amajeida; Salman, Abbas Abdulameer; Yusof, M. Sukeri M; Soh, Siti Kamilah Che; Ali, Hapipah Mohd; Sarip, Rozie

doi:10.2174/1874842201805010032

Cited by 7 publications

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“…In general, a substance is considered a good candidate for other studies if its LD 50 is three times higher than the minimum effective dose (19). Regarding acridine compounds, both low (14,15,20) and high toxicity (21,22) have been reported in literature.…”

Section: Discussionmentioning

confidence: 99%

Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions

et al. 2020

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Background/Aim: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4chlorobenzylidene)amino)-5 -4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound. Materials and Methods: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated. Results: AMTAC-06 did not induce toxicity on zebrafish and mice (LD 50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G 1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an antiangiogenic action, possibly dependent on the cytokine modulation . No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals. Conclusion: AMTAC-06 has low toxicity and a significant antitumor activity.The mechanisms underlying the transformation of normal cells into malignant cells have been thoroughly studied, aiming to better understand the biology of cancer and develop new treatments. Researchers have described common traits acquired during tumorigenesis, including sustaining proliferative signaling, induction of angiogenesis, deregulation of cell cycle, resistance to cell death and tumorpromoting inflammation (1-3). These hallmarks are important therapeutic targets for new antitumor drug development (3,4).Acridines are heterocyclic molecules containing a planar ring, which have shown anti-inflammatory, anticancer, antiparasitic, antiviral, and antimicrobial activities, among others (5). Their antitumor action is based on DNA binding and topoisomerase inhibition (6), which may cause apoptosis and cell cycle arrest (7). Nevertheless, acridine compounds 5049

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Section: Discussionmentioning

confidence: 99%

Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions

et al. 2020

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“…Acridine derivatives with substitutes at this position are characterized by marked antibacterial (Chen et al, 2019; Hamzi et al, 2013; Kudryavtseva, Bogatyrev, Sysoev, & Klimova, 2019; Sing, Kumar, Prasad, Sharma, & Silakari, 2011), antiviral (Lyakhov, Suveyzdis, Litvinova, Rybalko, & Dyadyun, 2000), anticancer (Cholewinski, Dzierzbicka, & Kolodziejczyk, 2011; de Mela Rego, de Sena, Moura, Jacob, et al, 2017; Demeunynck, Charmantray, & Martelli, 2001; Ismail et al, 2018; Kumar et al, 2017; Prajapati et al, 2017), antiprotozoal, antioxidant, antimalarial, antihelmintic, insectidal, fungicidal, and many other interesting biochemical and physical properties (Agili, 2018; Habeeb Unnisa Begum Nagma Fathima, Tasleem, 2018; Rupar, Dobričić, Aleksić, Brborić, & Čudina, 2018) (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

A new look at 9‐substituted acridines with various biological activities

Kožurková

Sabolová

Kristián

2020

J of Applied Toxicology

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Heterocycles have long been the focus of intensive study in attempts to develop novel therapeutic compounds, and acridine, a polynuclear nitrogen molecule containing a heterocycle, has attracted a considerable amount of scientific attention. Acridine derivatives have been studied in detail and have been found to possess multitarget properties, which inhibit topoisomerase enzymes that regulate topological changes in DNA and interfere with the essential biological function of DNA. This article describes some recent advancements in the field of new 9-substituted acridine heterocyclic agents and describes both the structure and the structure-activity relationship of the most promising molecules. The article will also present the IC 50 values of the novel derivatives against various human cancer cell lines. The mini review also investigates the topoisomerase inhibition and antibacterial and antimalarial activity of these polycyclic aromatic derivatives.

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“…Such substitution patterns would affect and improve biological activity. Based on the forementioned information, it might be assumed that the installation of biologically effective N-heterocyclic scaffolds with natural origin such as quinoline 39 , acridine 40 and neocryptolepine 41 motifs into the coumarin core structure would improve the coumarin pharmacological profile as anticancer and antimicrobial agent with synergistic effects when compared with each moiety separately as depicted in Fig. 1.…”

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Synthesis and in-vitro anti-proliferative with antimicrobial activity of new coumarin containing heterocycles hybrids

Abdelaziz,

El-Deeb,

Zayed

et al. 2023

Sci Rep

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A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a–e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized and evaluated for their anticancer and antimicrobial activities. The structures of all synthesized hybrids were confirmed by FT-IR, 1H-NMR, 13C-NMR, and MS spectrometry. The anti-proliferative activity of hybrids 7a–e, 10c and 13c were bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), and hepatocellular carcinoma (HepG-2) human cancer cell lines using doxorubicin as a reference drug. The results demonstrated that, all hybrids displayed moderate to good anti-proliferative activity against the cell lines. The most active hybrids were 7a–d and 10c against CaCo-2 cancer cell line with IC50: 57.1, 52.78, 57.29, 51.95 and 56.74 µM, and selectivity index 1.38, 1.76, 2.6, 1.96 and 0.77; respectively. While, 7a,d were potent against A549 cancer cell line with IC50: 51.72, 54.8 µM and selectivity index 1.5, 0.67; respectively. Moreover, 7c showed the most potency against MDA-MB-231 cancer cell line with IC50: 50.96 µM and selectivity index 2.20. Interestingly, docking results revealed that binding energy of the current compounds showed marked affinity values ranging from -6.54 to -5.56 kcal with interactions with the reported key amino acid SER 79. Furthermore, the antimicrobial activity of the synthesized hybrids 7a–e, 10b,c, 13b and 13c were evaluated against Gram‐positive and Gram‐negative bacterial and fungal strains. The hybrids 10b, 13b, 10c, and 13c exhibited broad-spectrum antibacterial activity against E.coli, S. mutans, and S. aureus with MIC from 3.2 to 66 µM, this hybrids also displayed antifungal activity against C. albicans with MIC values ranging from 0.0011 to 29.5 µM. In-silico investigation of the pharmacokinetic properties indicated that tested hybrids had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition to cell membrane penetrability.

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The Synthesis of a Novel Anticancer Compound, N-(3,5 Dimethoxyphenyl) Acridin-9-Amine and Evaluation of Its Toxicity

Cited by 7 publications

References 0 publications

Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions

Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions

A new look at 9‐substituted acridines with various biological activities

Synthesis and in-vitro anti-proliferative with antimicrobial activity of new coumarin containing heterocycles hybrids

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