Carbazole scaffolds in cancer therapy: a review from 2012 to 2018

Issa, Samar; Prandina, Anthony; Bedel, Nicolas; Rongved, Pål; Yous, Saı̈d; Borgne, Marc Le; Bouaziz, Zouhair

doi:10.1080/14756366.2019.1640692

Cited by 114 publications

(73 citation statements)

References 89 publications

(101 reference statements)

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“…Fungi in the Candida genus are the most common fungal pathogens which can colonize various host niches (stomach, vagina, and oral mucosa) with varying ambient pH range 1 . Drug molecules with the carbazole framework possess a wide range of biological and pharmacological activities [37][38][39][40] . Thus, the antiproliferative activity of 3,6-PIRAMICAR and its substrates was evaluated against human non-small cell lung cancer (A549) and colorectal carcinoma cell line (HCT116) for 72 h, using MTT assay.…”

Section: Biological Evaluationmentioning

confidence: 99%

Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent

Chylewska

Dąbrowska

Ramotowska

et al. 2020

Sci Rep

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Carbazole skeleton plays a significant role as a structural scaffold of many pharmacologically active compounds. Pyrazine-functionalized carbazole derivative was constructed by coupling 2-amino-5-bromo-3-methylaminepyrazine (ABMAP) into 3 and 6 positions of the carbazole ring. Multiexperimental methods were used, e.g., potentiometric, spectroscopic (ATR, UV, XRD powder, 1 H and 13 C NMR), electrochemical (cyclic voltammetry), and optical techniques, to receive the complete structural analysis, physicochemical (pKa, logP) and biological profile of a new carbazole derivative with acronym 3,6-PIRAMICAR. the interaction ability of the compound studied with potential cellular targets like Calf Thymus DNA (CT-DNA), or BovineSerumAlbumin (BSA) were also taken into account. experiments showed the existence of strong binding, but no DnA or BSA cleavage was observed. the comparative analyzes of compounds anti-Candida action clearly show pH-dependent antifungal activity of 3,6-PIRAMICAR , which was strongly stimulated in the acidic media. Surprisingly, the titled compound turn out to be much more effective (14 times by MIC50; 8 times by MIC; c.a. 4 times by MFC) against Candidakrusei than fluconazole at pH 4. The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases, is a major global problem, especially for immuno-deficient populations. The development of new antifungal agents in clinical trials is problematic inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms are based on certain characteristics of the fungus in order to avoid biological similarities with the host 1. Fungi in the Candida genus are the most common fungal pathogens which can colonize various host niches (stomach, vagina and oral mucosa) with varying ambient pH range 2-6. Carbazoles and derivatives with carbazole skeleton are currently tested intensively according to their antimicrobial properties which is directly relating with their structure or in more details with anaromatic N-heterocyclic ring inside 7. Carbazole derivatives have been reported to be potential agents against tumor 8 or opportunistic infections of AIDS 9,10. The studies about high active DNA intercalators show the significance of the carbazole structural agents like planarity or aromaticity 11,12. Interestingly, the mentioned parameters are described as responsible for the high affinity of carbazoles substituted at 3,6-or 2,7-positions by amine, amidine, or imidazoline groups to GC or AT-rich sequences of DNA 13,14. However, chemistry of especially di-substituted 3,6-derivatives of carbazole is still not very extensively explored due to problems with synthesis of such compounds. Mainly nitrogen atom was a hot spot for carbazole derivatives 14. The first concept of the studies was to check the basic design structures assumptions to predict pharmaceuticals activity, like presented carbazole functionalized by pyrazines-our previous research objects. Consequently, the confirmation of the possibili...

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Section: Biological Evaluationmentioning

confidence: 99%

Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent

Chylewska

Dąbrowska

Ramotowska

et al. 2020

Sci Rep

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“…[4] Furthermore, several synthetic pharmaceuticals carry this heterocycle. [5] Figure 1 shows four naturally occurring and syn- cyclic ketone with propanoic ester moiety, which is the product of the conjugated addition of cyclohexanone to ethyl acrylate. Furthermore, benzannulated congeners as well as a pyrido [4,3-b]indole derivative were accessed.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Hexahydrocarbazole Derivatives by Reductive Indolization

et al. 2020

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The reductive indolization is a two‐step protocol performed in one flask: First, the acid‐mediated Fischer indolization of a cyclic ketone with phenylhydrazine forms an iminium ion which is subsequently reduced by a hydrido borate reagent to the indoline as the final product. We utilized this new strategy for the preparation of hexahydrocarbazole derivatives with a side chain in the quaternary C4a‐position. Starting materials were several N1‐ and aryl‐substituted phenylhydrazines and a cyclic ketone with propanoic ester moiety, which is the product of the conjugated addition of cyclohexanone to ethyl acrylate. Furthermore, benzannulated congeners as well as a pyrido[4,3‐b]indole derivative were accessed. The hexahydrocarbazole defines a molecular scaffold with two points of diversification. Therefore, several derivatives at N9 and at the C4a‐side chain were prepared.

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“…It acts as topoisomerase II inhibitor and DNA intercalating agent. [15] While, Clauszoline-I, is a natural antineoplastic carbazole product that induces cell cycle arrest in the S and G2/M phases by inhibiting the serine/threonine kinases. [16] On the other hand, the antiproliferative carbazole derivative EHop-016 acts as Rac1 inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Antitumor Evaluation of Some Carbazole‐Based Thiazole, Thiophene, and 1,3,4‐Thiadiazole Derivatives

2020

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In continuation to our efforts to discover new powerful antitumor agents, a series of new carbazole-based thiazole, thiophene, and 1,3,4-thiadiazole derivatives were conveniently synthesized, spectrally characterized, and mechanistically discussed. The synthetic strategy involves the cyclization reactions of two easily attainable commencing materials, N-(9-ethylcarbazol-3-yl)-2-cyanoacetamide (1) and 2-((9-ethylcarbazol-3yl)hydrazono)-3-oxo-N-phenylbutanethioamide (20), with αchlorocarbonyl reagents, α-chloronitrile, and hydrazonoyl chlorides in a basic medium. They were also assessed against three human tumor cell lines (HCT-116, HepG-2, and MCF-7) and one non-tumor human cell line (REP1) for their in vitro antitumor activity. The results demonstrated that seven carbazoles 4, 15 a, 15 b, 15 d, 20, 22 b, and 29 a had high antitumor activity, having IC 50 values in the range 5.24-9.70 μM. The most potent carbazoles 15 b, 20 and 22 b inhibited the growth of all tested tumor cell lines and did not display human toxicity.

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Carbazole scaffolds in cancer therapy: a review from 2012 to 2018

Cited by 114 publications

References 89 publications

Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent

Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent

Preparation of Hexahydrocarbazole Derivatives by Reductive Indolization

Synthesis and In Vitro Antitumor Evaluation of Some Carbazole‐Based Thiazole, Thiophene, and 1,3,4‐Thiadiazole Derivatives

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