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

Demurtas, Monica; Baldisserotto, Anna; Lampronti, Ilaria; Moi, Davide; Balboni, Gianfranco; Pacifico, Salvatore; Vertuani, Silvia; Manfredini, Stefano

doi:10.1016/j.bioorg.2019.02.007

Cited by 94 publications

(44 citation statements)

References 48 publications

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“…Cytotoxic activity against Colo-38 cells of human melanoma has led to the identification of derivatives belonging to the three different series, with a promising antitumor profile. The best IC 50 values were obtained for the derivatives bearing the 2-hydroxy-4-(diethylamino) moiety: the IC 50 data of the derivative 13 (0.50 µM) is in line with the values obtained from the derivatives of the previous series [24,25].…”

Section: Discussionsupporting

confidence: 82%

“…A high activity had instead been found for the 2-hydroxy-4-(diethylamino)benzylidene derivative. The SAR study on indole derivatives [25] had led to the same conclusions, also underlining the contribution of a methoxy group in position 4 to the activity under consideration. The antioxidant data deriving from the study of benzimidazolehydrazone derivatives again confirm what reported by the previous series.…”

Section: Discussionmentioning

confidence: 63%

“…On the other hand, also hydrazone moieties are endowed with potent antioxidant potency [20][21][22][23]. Based on these findings and as a continuation of our works on antioxidant agents [24][25][26], here we report and discuss the antioxidant properties of benzimidazolehydrazones containing a phenolic group and their structure-activity relationships (SAR). The studied molecules have been synthesized and chemically characterized by us during a previous synthetic study [27], but not fully investigated for their activity.…”

Section: Introductionmentioning

confidence: 76%

“…Research aimed at the development of multifunctional molecules has been at the center of our work for years [24,25,27] and has led us to investigate different scaffolds such as benzimidazole, benzofurane and indole nuclei, which are however connected by an hydrazone linker and an aromatic nucleus, differently substituted, considering the importance of fractions suitable to extend the conjugation to the aromatic ring. All the derivatives have been tested for their potential antioxidant, UV filtering and anti-proliferative activity (in particular against melanoma cells).…”

Section: Discussionmentioning

confidence: 99%

“…The protocol used for the release experiments followed the one previously reported [25] with the variation of the receiving solution: in this case in fact the receiving solution was Buffer phosphate 1M pH 11.2 for Oxisol, and pH 11.7 for compounds 9 and 13. 0.5 g of each formulation was placed in the donor compartment in contact with the membrane positioned between the two compartments.…”

Section: Franz Cells Apparatusmentioning

confidence: 99%

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In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

et al. 2020

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In the search of multifunctional compounds we designed benzimidazole derivatives endowed with phenolic hydroxy groups and a hydrazone moiety as potential radical-scavenger and the antioxidant agents. The target molecules have been prepared by a simple synthetic procedure and tested for their antioxidant activity by DPPH, FRAP, and ORAC test, for photoprotective activity against UV rays and for antiproliferative activity against Colo-38 melanoma cells. Furthermore, two different dermocosmetic formulations were prepared with the compounds endowed with the best antioxidant and photoprotective profile and their release from formulation evaluated using Franz Cells system. High antioxidant activity is related to the presence of at least two hydroxy groups on arylidene moiety of benzimidazoles. Structure activity analysis revealed that the position of hydroxy groups is crucial for antioxidant activity as well as the presence of a 2-hydroxy-4-(diethylamino)arylidene group. The same correlation pattern was found to be related to photoprotective activity resulting in an UVA Protection Factor better than the commercial solar filter PBSA and antiproliferative activity against melanoma cells without producing cytotoxicity on normal keratinocytes. The release analysis indicated that high antioxidant activities are achieved with limited release at concentration compatible with the use as UV sunscreen filter.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Franz Cells Apparatusmentioning

confidence: 99%

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In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

et al. 2020

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Synthesis of Selenocyanated Indoles via PhICl₂‐Induced Electrophilic Intramolecular Cyclization of 2‐Alkynylanilines or 2‐Alkenylanilines

Xu,

Zhao,

Zhao

et al. 2024

Asian J Org Chem

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The 3‐selenocyanato‐substituted indoles were readily synthesized via PhICl2‐induced reaction of 2‐alkynylanilines or 2‐alkenylanilines with KSeCN in MeCN under metal‐free conditions. The reaction sequence was postulated to encompass the formation of a reactive selenocyanogen chloride species, generated in situ from the reaction of PhICl2 and KseCN, followed by electrophilic addition and intramolecular cyclization steps.

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A novel bidentate ligand containing oxime, hydrazone and indole moieties and its BF₂⁺ bridged transition metal complexes and their efficiency against prostate and breast cancer cells

Babahan

Özmen

Aksel

et al. 2020

Applied Organom Chemis

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In this study, a novel bidentate ligand containing oxime, hydrazone, and indole moieties and its BF2+‐bridged transition metal complexes [Ni(II), Cu(II), and Co(II)] were synthesized and their cytotoxic activities against prostate and breast cancer cells were investigated. The vic‐dioxime ligand bearing indole–hydrazone side groups was synthesized by reacting antiglyoximehydrazine (GH2) with 3‐methoxy indole. The ligand forms mononuclear complexes with a metal‐to‐ligand ratio of 1:2 with M = Co(II)(H2O)2, Ni(II), and Cu(II). These metal complexes were then reacted with BF3(C2H5)2O to obtain BF2+‐bridged transition metal complexes. The Co(II) complex of the ligand is proposed to be octahedral with water molecules as axial ligands, whereas the Ni(II) and Cu(II) complexes are proposed to be square planar. Spectral studies showed that the ligand bonded to the metal ion in a neutral bidentate fashion through the azomethine nitrogen atom and the imine oxime group. Structural assignments are supported by a combination of 1H nuclear magnetic resonance (NMR), 13C NMR, Fourier‐transform infrared, LC/MS, elemental analyses, and magnetic susceptibility testing. For determining the cytotoxic effects of the novel anticancer products, cancer cells were cultured. The antiproliferative effects were determined using the MCF‐7 breast cancer and PC‐3 prostate cancer cell lines. The antiproliferative effects of the products were analyzed and their apoptotic or necrotic effects were determined with the Hoechst/propidium iodide double staining method in both cancer cell lines. Paclitaxel was used as the positive control (1 μm). The results indicated that the newly synthesized compounds are effective on both cell lines between concentrations of 5 and 40 μm and show their effects by apoptotic mechanisms. Besides, these products were found to be more effective on the MCF‐7 cell line. The cytotoxic efficiency of the newly synthesized products was more than that of paclitaxel (depending on concentration), which is a chemotherapeutic agent used in cancer therapy.

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

Cited by 94 publications

References 48 publications

In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

Synthesis of Selenocyanated Indoles via PhICl₂‐Induced Electrophilic Intramolecular Cyclization of 2‐Alkynylanilines or 2‐Alkenylanilines

A novel bidentate ligand containing oxime, hydrazone and indole moieties and its BF₂⁺ bridged transition metal complexes and their efficiency against prostate and breast cancer cells

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

Cited by 94 publications

References 48 publications

In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

Synthesis of Selenocyanated Indoles via PhICl2‐Induced Electrophilic Intramolecular Cyclization of 2‐Alkynylanilines or 2‐Alkenylanilines

A novel bidentate ligand containing oxime, hydrazone and indole moieties and its BF2+ bridged transition metal complexes and their efficiency against prostate and breast cancer cells

Contact Info

Product

Resources

About

Synthesis of Selenocyanated Indoles via PhICl₂‐Induced Electrophilic Intramolecular Cyclization of 2‐Alkynylanilines or 2‐Alkenylanilines

A novel bidentate ligand containing oxime, hydrazone and indole moieties and its BF₂⁺ bridged transition metal complexes and their efficiency against prostate and breast cancer cells