Synthesis of New Functionalized Indoles Based on Ethyl Indol-2-carboxylate

Boraei, Ahmed T. A.; Ashry, El Sayed H. El; Barakat, Assem; Ghabbour, Hazem A.

doi:10.3390/molecules21030333

Cited by 14 publications

(11 citation statements)

References 32 publications

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“…1H-Indole-2-carboxylic acid (1) was converted into ethyl ester (2) [30]. The ethanolic solution of intermediate 2 and hydrazine hydrate was refluxed to achieve 1H-Indole-2-carbohydrazide (3) [31]. Hydrazones 4-17 were obtained in good to excellent The IR and NMR spectral data are consistent with the assigned structure.…”

Section: Chemistrymentioning

confidence: 66%

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Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones

Demurtas

Baldisserotto

Lampronti

et al. 2019

Bioorganic Chemistry

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Section: Chemistrymentioning

confidence: 66%

“…Ethyl 1H-Indole-2-carboxylate (2) was prepared as previously described [30] starting from 1H-Indole-2carboxylic acid. 1H-Indole-2-carbohydrazide (3) was prepared as previously described [31].…”

Section: Antiproliferative Activity On Human Melanoma Colo38 and Eryt...mentioning

confidence: 99%

Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones

Demurtas

Baldisserotto

Lampronti

et al. 2019

Bioorganic Chemistry

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“…As part of our current studies on the development of new routes in heterocyclic synthesis, − here we focused on the synthesis of new heterocyclic systems from ninhydrin. Stirring ninhydrin 1 with ethyl acetoacetate 2 in water for 15 min afforded ethyl indeno[1,2- b ]furan-3-carboxylate 3 in excellent yield .…”

Section: Resultsmentioning

confidence: 99%

Expeditious Green Synthesis of Novel 4-Methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one Analogue from Ninhydrin: N/S-Alkylation and Aza-Michael Addition

et al. 2020

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A straightforward green synthesis of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 6 is reported from ninhydrin 1 via condensation with ethyl acetoacetate, followed by cyclization with hydrazine hydrate in water as a benign solvent. Tetraazafluoranthen-3-thione 7 was obtained using Lawesson's reagent. N-alkylated tetraazafluoranthen-3-one 8−12 and Salkylated analogues 13−15 were synthesized via alkylation. The investigation of the unique reactivity of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one/ thione toward the alkylation and aza-Michael additions was explored.

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“…Reaction mixture was allowed to reflux with continuous stirring for about 1.5 h and poured into ice/water mixture. The precipitate was filtered, washed with cold water and purified by flash column chromatography using gradient elution of EtOAc: n -hexane to give the corresponding carbohydrazide [ 67 , 68 , 69 ].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, Anticancer Activity, and Solid Lipid Nanoparticle Formulation of Indole- and Benzimidazole-Based Compounds as Pro-Apoptotic Agents Targeting Bcl-2 Protein

et al. 2021

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Cancer is a multifactorial disease necessitating identification of novel targets for its treatment. Inhibition of Bcl-2 for triggered pro-apoptotic signaling is considered a promising strategy for cancer treatment. Within the current work, we aimed to design and synthesize a new series of benzimidazole- and indole-based derivatives as inhibitors of Bcl-2 protein. The market pan-Bcl-2 inhibitor, obatoclax, was the lead framework compound for adopted structural modifications. The obatoclax’s pyrrolylmethine linker was replaced with straight alkylamine or carboxyhydrazine methylene linkers providing the new compounds. This strategy permitted improved structural flexibility of synthesized compounds adopting favored maneuvers for better fitting at the Bcl-2 major hydrophobic pocket. Anti-cancer activity of the synthesized compounds was further investigated through MTT-cytotoxic assay, cell cycle analysis, RT-PCR, ELISA and DNA fragmentation. Cytotoxic results showed compounds 8a, 8b and 8c with promising cytotoxicity against MDA-MB-231/breast cancer cells (IC50 = 12.69 ± 0.84 to 12.83 ± 3.50 µM), while 8a and 8c depicted noticeable activities against A549/lung adenocarcinoma cells (IC50 = 23.05 ± 1.45 and 11.63 ± 2.57 µM, respectively). The signaling Bcl-2 inhibition pathway was confirmed by molecular docking where significant docking energies and interactions with key Bcl-2 pocket residues were depicted. Moreover, the top active compound, 8b, showed significant upregulated expression levels of pro-apoptotic/anti-apoptotic of genes; Bax, Bcl-2, caspase-3, -8, and -9 through RT-PCR assay. Improving the compound’s pharmaceutical profile was undertaken by introducing 8b within drug-solid/lipid nanoparticle formulation prepared by hot melting homogenization technique and evaluated for encapsulation efficiency, particle size, and zeta potential. Significant improvement was seen at the compound’s cytotoxic activity. In conclusion, 8b is introduced as a promising anti-cancer lead candidate that worth future fine-tuned lead optimization and development studies while exploring its potentiality through in-vivo preclinical investigation.

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Synthesis of New Functionalized Indoles Based on Ethyl Indol-2-carboxylate

Cited by 14 publications

References 32 publications

Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones

Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones

Expeditious Green Synthesis of Novel 4-Methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one Analogue from Ninhydrin: N/S-Alkylation and Aza-Michael Addition

Design, Synthesis, Anticancer Activity, and Solid Lipid Nanoparticle Formulation of Indole- and Benzimidazole-Based Compounds as Pro-Apoptotic Agents Targeting Bcl-2 Protein

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