Design, synthesis and evaluation of novel (S)-tryptamine derivatives containing an allyl group and an aryl sulfonamide unit as anticancer agents

Guo, Zhiyong; Xu, Yiming; Peng, Yujie; Rashid, Haroon Ur; Quan, Wei; Xie, Peng; Wu, Li; Jiang, Jun; Wang, Lisheng; Liu, Xu

doi:10.1016/j.bmcl.2019.02.023

Cited by 22 publications

(10 citation statements)

References 24 publications

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“…Whereas derivative 4g bearing an electron‐withdrawing group (COOH) displayed a slight reduction in the anticancer activity with an IC 50 value in range 6.78— 10.39 μM, but was still more active than compounds 4a — 4c . Derivative 4i bearing ally motif exhibited good antitumor behavior (IC 50 ranged between 6.71 and 9.82 μM) towards three tested cell lines that confirmed the advantageous role of the allyl group for cancer treatment . To our delight, bis‐chloropyridine dicarbonitriles ( 4j — 4l , class D) demonstrate a selective cytotoxic behavior on the screened cancer cell lines.…”

Section: Resultssupporting

confidence: 53%

“…Moreover, among compounds 4f — 4i , derivatives 4h and 4f those comprising electron‐donating moieties, viz cyclohexyl and methyl, respectively exhibited a better cytotoxic effect. An obvious characteristic is that electron‐donating groups could significantly improve lipotropy which in turn is responsible for enhancement of cytotoxic activity . Whereas derivative 4g bearing an electron‐withdrawing group (COOH) displayed a slight reduction in the anticancer activity with an IC 50 value in range 6.78— 10.39 μM, but was still more active than compounds 4a — 4c .…”

Section: Resultsmentioning

confidence: 99%

“…Pyridines are among the most important biochemical scaffolds with broader uses in the medicinal and pharmaceutical industries as well as intermediates in heterocyclic preparations . Among pyridine derivatives, dicyanopyridines act as ‘privileged skeleton’ owing to their prospective uses for therapy . These derivatives were recorded to serve as anti‐prion, human adenosine A2B receptor, antibacterial, anti‐cancer, and anti‐hepatitis B virus .…”

Section: Background and Originality Contentmentioning

confidence: 99%

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Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents

Arafa

Hussein

2020

Chin. J. Chem.

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of main observation and conclusion A highly efficient, simple, and clean single-step sonosynthetic procedure has been sophisticated for assembling new series of mono-and bis-pyridine dicarbonitriles from ketones, HCl, and tetracyanoethylene. The presented protocol is applicable for the preparation of a broad range of uniquely substituted pyridine dicarbonitriles and seems to be superior in comparison with other previously reported methods. The antiproliferative impact of the newly synthesized derivatives was screened towards three representative cancer cell lines (MCF-7, A549, and HCT116). Most of the evaluated derivatives showed a moderate to excellent anti-proliferative activity towards the selected cell lines. Of these, compounds 4h, 4k, 10, 12a, and 12b showed both potent anticancer activity (IC50<10 μM) and lower cytotoxic effect (IC50 > 58 μM) on non-tumorigenic cells (MCF-10A and NCM460), suggesting their promising potential to be lead molecules for future antitumor drug discovery. The structure-activity relationships have been also discussed. Moreover, quantum chemical studies based on Density Functional Theory (DFT) of the synthesized compounds were investigated and found to be consistent with the in vitro inhibitory activities. Results and DiscussionPreparation of 6-chloro-[2,2'-bipyridine]-4,5-dicarbonitrile (4a) by treatment of tetracyanoethylene (1, TCNE, 1.0 mmol), and 2-acetyl pyridine (2a, 1.0 mmol) with HCl (3.0 mL) was chosen as the template reaction (Scheme 1) under silent (70 o C) and ultra-502 www.cjc.wiley-vch.de

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Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Background and Originality Contentmentioning

confidence: 99%

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Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents

Arafa

Hussein

2020

Chin. J. Chem.

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“…Tryptamine is the most important member of the indole amine family. The tryptamine scaffold is regarded as a structure of priority importance due to its broad applications in the design of medicinal agents [ 11 ]. Tryptamine analogues have been reported to display pharmacological activity, such as anti-migraine [ 12 ], antibacterial [ 13 , 14 ] and antitumor effects [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Oleanolic Acid-Tryptamine and -Fluorotryptamine Amides: From Adaptogens to Agents Targeting In Vitro Cell Apoptosis

Bildziukevich

Kvasnicová

Šaman

et al. 2021

Plants

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Background: Oleanolic acid is a natural plant adaptogen, and tryptamine is a natural psychoactive drug. To compare their effects of with the effect of their derivatives, tryptamine and fluorotryptamine amides of oleanolic acid were designed and synthesized. Methods: The target amides were investigated for their pharmacological effect, and basic supramolecular self-assembly characteristics. Four human cancer cell lines were involved in the screening tests performed by standard methods. Results: The ability to display cytotoxicity and to cause selective cell apoptosis in human cervical carcinoma and in human malignant melanoma was seen with the three most active compounds of the prepared series of compounds. Tryptamine amide of (3β)-3-(acetyloxy)olean-12-en-28-oic acid (3a) exhibited cytotoxicity in HeLa cancer cell lines (IC50 = 8.7 ± 0.4 µM) and in G-361 cancer cell lines (IC50 = 9.0 ± 0.4 µM). Fluorotryptamine amides of (3β)-3-(acetyloxy)olean-12-en-28-oic acid (compounds 3b and 3c) showed cytotoxicity in the HeLa cancer cell line (IC50 = 6.7 ± 0.4 µM and 12.2 ± 4.7 µM, respectively). The fluorotryptamine amide of oleanolic acid (compound 4c) displayed cytotoxicity in the MCF7 cancer cell line (IC50 = 13.5 ± 3.3 µM). Based on the preliminary UV spectra measured in methanol/water mixtures, the compounds 3a–3c were also found to self-assemble into supramolecular systems. Conclusions: An effect of the fluorine atom present in the molecules on self-assembly was observed with 3b. Enhanced cytotoxicity has been achieved in 3a–4c in comparison with the effect of the parent oleanolic acid (1) and tryptamine. The compounds 3a–3c showed a strong induction of apoptosis in HeLa and G-361 cells after 24 h.

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“…Aryl/heteroaryl sulfonamides are versatile compounds of significant synthetic and biological properties that are widely applied . The synthesis of various sulfonamide derivatives has attracted substantial interest as many of them show wonderful anticancer activity in vitro and in vivo against diverse cancer cell lines . There are a number of mechanisms that illustrate the anticancer action of sulfonamides, including carbonic anhydrase inhibition, disruption of microtubule assembly, cell cycle release in the G1 phase, functional suppression of the transcriptional activator NF‐Y, and inhibition of angiogenesis among others .…”

Section: Introductionmentioning

confidence: 99%

Convenient synthesis of novel sulfonamide derivatives as promising anticancer agents

El‐Mekabaty

Awad

2019

Journal of Heterocyclic Chem

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Novel sulfonamide derivatives have been synthesized from the readily accessible N‐(4‐acetylphenyl)benzenesulfonamide (1). Condensation of 1 with phenylhydrazine in refluxing ethyl alcohol gave the corresponding phenylhydrazone 2, which was then added to the Vilsmeier‐Haack reagent (POCl3/DMF) to give the 4‐formylpyrazole derivative 3. Fusion of 1 with thiourea in the presence of iodine at 130°C afforded the 2‐aminothiazole derivative 4. Refluxing 1 with an excess of N, N‐dimethylformamide dimethyl acetal furnished the enaminone 5. The chemical reactivity of enaminone 5 toward some nitrogen and carbon nucleophiles has been studied to obtain polyfunctionalized heteroaromatic systems bearing a sulfonamide moiety. Besides, the enaminone 5 undergoes the Gewald reaction and reacts with ethyl cyanoacetate and elemental sulfur in the presence of morpholine to yield the 2‐aminothiophene derivative 18. Moreover, the utility of 5 for the synthesis of 4‐(phenylsulfonamido)benzoic acid (19) was investigated. The synthesized sulfonamides were evaluated for their in vitro cytotoxic activities against two human cell lines, MCF‐7 (breast adenocarcinoma cells) and RPE‐1 (normal retina pigmented epithelium cells). The results revealed that compounds 1‐3, 6‐8, 10, 12b, 18, 19, and 21 have a potent cytotoxic effect on MCF‐7 and less on RPE‐1 cells compared to the positive control doxorubicin®.

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Design, synthesis and evaluation of novel (S)-tryptamine derivatives containing an allyl group and an aryl sulfonamide unit as anticancer agents

Cited by 22 publications

References 24 publications

Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents

Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents

Novel Oleanolic Acid-Tryptamine and -Fluorotryptamine Amides: From Adaptogens to Agents Targeting In Vitro Cell Apoptosis

Convenient synthesis of novel sulfonamide derivatives as promising anticancer agents

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