Glioblastoma-specific anticancer activity of newly synthetized 3,5-disubstituted isoxazole and 1,4-disubstituted triazole-linked tyrosol conjugates

Aissa, Imen; Abdelkafi-Koubaa, Zaineb; Chouaïb, Karim; Jalouli, Maroua; Assel, Amine; Romdhane, Anis; Harrath, Abdel Halim; Marrakchi, Naziha; Jannet, Hichem Ben

doi:10.1016/j.bioorg.2021.105071

Cited by 11 publications

(7 citation statements)

References 42 publications

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“…This result indicated that 3d compound induced apoptosis in the K562 cells. This finding is in agreement with our previous study, showing that the molecule triggers anti-proliferative effects in U87 cells through the induction of apoptosis [21]. Our results are also consistent with other studies, which reported that isoxazole derivatives act as an anticancer agent inducing apoptosis [15,16].…”

Section: Compound 3d Induced Apoptosis In K562 Leukemia Cellssupporting

confidence: 94%

“…In agreement with our previous study, compounds with methyl, methoxy or chlorine substitution at R groups in isoxazole derivatives and compounds with a chlorine substitution at R groups in triazole derivatives were more effective against glioblastoma cells [21].…”

Section: Anti-proliferative Effect On K562 Cellssupporting

confidence: 93%

“…Two series of tyrosol derivatives bearing 3,5-disubstituted isoxazole (3a-e) and 1,4-disubstituted triazole (4a-e) were synthesized and characterized as described previously by Aissa et al [21]. Imatinib mesylate (STI571), used as a reference therapeutic molecule, Ficoll-Hypaque and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

Section: Chemical Reagentsmentioning

confidence: 99%

“…In a previous study, we reported on the synthesis of two series of 3,5-disubstituted isoxazole (3a-e) and 1,4-disubstituted triazole (4a-e) derivatives. Some derivatives inhibited significantly the proliferation of the U87 glioblastoma cell line with a pro-apoptotic activity [21], promoting a possible path for their further exploitation.…”

Section: Introductionmentioning

confidence: 98%

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Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis

et al. 2022

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In the present study, we assess tyrosol derivatives bearing 3,5-disubstituted isoxazoles and 1,4-disubstituted triazoles for their ability to inhibit the proliferation of K562 cells derived from leukemia as well as primary chronic myeloid leukemia (CML) cells obtained from the peripheral blood of 15 CML patients including 10 patients with untreated chronic phase and 5 patients with resistance against imatinib or multiple TKI. Our results showed that most derivatives displayed significant anti-proliferative activity against K562 cells in a dose-dependent manner. Among them, compounds 3d and 4a exhibited greater potent anticancer activity with respective IC50 values of 16 and 18 µg/mL (45 µM and 61 µM). Interestingly, compound 3d inhibited CML cell proliferation not only in newly diagnosed but also in imatinib-resistant patients. We demonstrated that the anti-proliferative effect of this compound is mediated by a pro-apoptotic activity by promoting oxidative stress and modulating the activity of the Akt, p38 MAPK and Erk 1/2 pathways. In conclusion, our data highlight the potential of this class of derivative as a novel promising therapeutic agent for CML therapy.

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Section: Compound 3d Induced Apoptosis In K562 Leukemia Cellssupporting

confidence: 94%

Section: Anti-proliferative Effect On K562 Cellssupporting

confidence: 93%

Section: Chemical Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis

et al. 2022

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“…Notably, the hemolytic activity of compound 53 caused hemolysis up to 40% at a concentration of 400 μg mL −1 . These results revealed that isoxazole derivatives did not damage red blood cells and release hemoglobin, which strengthened the potential of these compounds as innovatively synthesized anticancer prototypes with low toxicity [ 143 ].…”

Section: Hsp90 Inhibitorsmentioning

confidence: 90%

Heterocyclic Compounds as Hsp90 Inhibitors: A Perspective on Anticancer Applications

et al. 2022

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Heat shock proteins (Hsps) have garnered special attention in cancer therapy as molecular chaperones with regulatory/mediatory effects on folding, maintenance/stability, maturation, and conformation of proteins as well as their effects on prevention of protein aggregation. Hsp90 ensures the stability of various client proteins needed for the growth of cells or the survival of tumor cells; therefore, they are overexpressed in tumor cells and play key roles in carcinogenesis. Accordingly, Hsp90 inhibitors are recognized as attractive therapeutic agents for investigations pertaining to tumor suppression. Natural Hsp90 inhibitors comprising geldanamycin (GM), reclaimed analogs of GM including 17-AAG and DMAG, and radicicol, a natural macrocyclic antifungal, are among the first potent Hsp90 inhibitors. Herein, recently synthesized heterocyclic compounds recognized as potent Hsp90 inhibitors are reviewed along with the anticancer effects of heterocyclic compounds, comprising purine, pyrazole, triazine, quinolines, coumarin, and isoxazoles molecules.

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An Efficient Synthesis, Antimicrobial Evaluation and In Silico Studies of 1,2,3‐Triazolyl‐isoxazolyl‐ethanol Derivatives

Bhoye,

Latif Shaikh,

Walunj

et al. 2024

ChemistrySelect

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A series of 2‐(1‐substituted benzyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(5‐arylisoxazol‐3‐yl)ethanol (8 a–p) have been designed and efficiently synthesized. The structure of the compounds 8 a–p was characterized by spectral methods. The newly synthesized 1,2,3‐triazolyl‐isoxazolyl‐ethanol (8 a–p) derivatives were evaluated for in vitro antimicrobial activity against P. mirabilis, E. coli, S. albus, B. subtilis, C. albicans and A. niger. Eleven derivatives showed good activity against the Gram‐negative strains. Compounds 8 b, 8 c, 8 d, 8 g, 8 h, 8 i, 8 j, 8 k, 8 n, 8 o, and 8 p showed good antibacterial against E. coli activity. Against P. mirabilis, compounds 8 a, 8 b, 8 d, 8 g, 8 h, 8 k, 8 l, 8 m, 8 n, 8 o, and 8 p showed good activity, compounds 8 o, and 8 p showed two‐fold less activity than the reference drug streptomycin. Against the Gram‐positive strain, B. subtilis, compounds 8 c, 8 d and 8 f showed good activity, from which the compounds 8 d and 8 f were found only two‐fold less potent than the reference drug streptomycin. Against fungal strains, C. albicans, compound 8 g and against A. niger, compounds 8 f, 8 h and 8 j showed good antifungal activity. Against A. niger strain, the compounds 8 f and 8 h reported only two‐fold less activity than the reference drug fluconazole. The active compounds were studied for molecular docking and molecular dynamics simulations.

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Glioblastoma-specific anticancer activity of newly synthetized 3,5-disubstituted isoxazole and 1,4-disubstituted triazole-linked tyrosol conjugates

Cited by 11 publications

References 42 publications

Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis

Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis

Heterocyclic Compounds as Hsp90 Inhibitors: A Perspective on Anticancer Applications

An Efficient Synthesis, Antimicrobial Evaluation and In Silico Studies of 1,2,3‐Triazolyl‐isoxazolyl‐ethanol Derivatives

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