Design, Hemiysnthesis, crystal structure and anticancer activity of 1, 2, 3-triazoles derivatives of totarol

Laamari, Yassine; Oubella, Ali; Bimoussa, Abdoullah; Mansouri, Az-Eddine El; Ketatni, El Mostafa; Mentré, Olivier; Itto, My Youssef Ait; Morjani, Hamid; Khouili, Mostafà; Auhmani, Aziz

doi:10.1016/j.bioorg.2021.105165

Cited by 29 publications

(16 citation statements)

References 60 publications

(30 reference statements)

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“…Moreover, alongside the after-mentioned interactions for ligand 7 b, the introduction of thiazole in compound 7 b showed two additional Pi-sulfur and PiÀ Pi T-shaped into reactions with Cys163 and His121, which are among the key amino acids responsible for the caspase-3 activation. [50][51][52][53][54][55] Overall, molecular docking suggested that the anticancer activities of products 2 b and 7 b could be at least mediated by activating caspase-3 protein after binding to its active site.…”

Section: Molecular Docking Studymentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

et al. 2022

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Herein, we report the synthesis of a novel series of βhimachalene derivatives, including semicarbazones, thiosemicarbazones, and thiazoles. The structures of these compounds were elucidated by NMR, IR, and HRMS analysis methods. The in vitro antitumor activity of these compounds was evaluated by the MTT assay against four human cancer cell lines, such as fibrosarcoma (HT-1080), breast adenocarcinoma (MCF-7 and MDA-MB-231), and lung carcinoma (A-549), and the results indicated that all compounds showed moderate to significant cytotoxic activities against all cancer cell lines with IC 50 values ranging from 7.19 � 0.30 to 50 μM. The mechanism of action of the most cytotoxic compounds 2 b and 7 b suggested that they induced apoptosis through caspase-3/7 activation, and elicited G2/M-phase arrest with the loss of mitochondrial membrane potential in HT-1080 cells. The molecular docking showed that compounds 2 b and 7 b activated the caspase-3 by forming a stable protein-ligand complex.

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Section: Molecular Docking Studymentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

et al. 2022

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“…Frontier molecular orbitals (FMOs) namely highest occupied orbital (HOMO) and lowest unoccupied orbital (LUMO) are the most important orbital in molecule. The ΔE gap is considered a highly effective parameter for explaining transfer interaction within the molecule [27,28] . The XRD data were used to build the structure of compounds and the geometries were optimized by applying DFT/B3LYP/6‐311G(d, p) levels of theory.…”

Section: Resultsmentioning

confidence: 99%

Novel Hydrazono‐2‐Iminothiazolidin‐4‐Ones Based on a Monoterpenic Skeleton as Potential Antitumor Agents: Synthesis, DFT Studies, in Vitro Cytotoxicity, Apoptosis Inducing Properties and Molecular Docking

Auhmani

Fawzi

Oubella

et al. 2022

Chemistry & Biodiversity

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A series of novel 2‐iminothiazolidin‐4‐one analogs have been synthesized from limonaketone, and structurally characterized by HR‐MS, 1H‐NMR and 13C‐NMR spectroscopy techniques, and the structure of compound 4 was elucidated by XRD. The newly synthesized products were biologically evaluated in vitro for their cytotoxic activity against human cancer cell lines HT‐1080, A549, and MCF‐7. Thiazolidinones 9 and 10 were the most active compounds in HT‐1080 cell lines (IC50=15.85±1.75 and 16.13±1.55 μM, respectively). The apoptosis induction of the derivatives 9 and 10 were studied using annexin V staining, caspase‐3/7 activity and cell cycle analysis. Compound 10 showed the highest ability of apoptosis induction and caspase‐3/7 activation associated with S‐phase growth arrest in HT‐1080. Meanwhile, compound 9 has a moderate apoptotic effect and G0/G1‐phase arrest in the after‐mentioned cell. The molecular docking suggested that compounds 9 and 10 formed stable ligand‐caspase‐3 complexes. Besides, the presence of phenyl moiety in ligand 10 is responsible for the enhancement of the caspase‐3 activation by the apparition of two additional hydrogen bonds with Cys163 and Gln161amino acids.

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“…The efficient and regiospecific alkyne-azide-click reaction, also known as the Cu-catalyzed Alkyne-Azide Cycloaddition reaction (CuAAC), has become a common approach for the stereoselective synthesis of the 1,4 regioisomer of 1,2,3-triazoles. As a part of our efforts toward the synthesis of new bioactive heterocyclic systems with a basic terpenic skeleton [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], we have recently reported the interesting anticancer activities of some 1,4-disubstituted 1,2,3-triazolic compounds newly prepared from Eugenol and (R)-carvone monoterpene [ 38 , 39 ]. These promising findings prompt us to extend our interest in the synthesis ofother 1,4-disubstituted 1,2,3-tiazoles from another natural monoterpene.…”

Section: Introductionmentioning

confidence: 99%

New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation

Oubella¹,

Bimoussa²,

Oussidi³

et al. 2022

Molecules

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Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide–alkyne cycloaddition reaction using CuSO4,5H2O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a–h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC50 values of 25.77 and 27.89 µM, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC50 value of 25.03 µM. Density functional calculations at the B3LYP/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal/mol and 29.35 kcal/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction.

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Design, Hemiysnthesis, crystal structure and anticancer activity of 1, 2, 3-triazoles derivatives of totarol

Cited by 29 publications

References 60 publications

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

Novel Hydrazono‐2‐Iminothiazolidin‐4‐Ones Based on a Monoterpenic Skeleton as Potential Antitumor Agents: Synthesis, DFT Studies, in Vitro Cytotoxicity, Apoptosis Inducing Properties and Molecular Docking

New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation

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