Discovery of potent and selective Bcl-2 inhibitors with acyl sulfonamide skeleton

Wang, Bin; Feng, Weiwei; Wang, Jinan; Dong, Yuanzhen; Liu, Yanlong; Yao, Yu; Shi, Wei; Liu, Limin; Zhang, Hongying; He, Xiangyi; Chang, Xiayun; Wang, Xiaojin; Xu, Hongjiang; Liu, Fei; Feng, Jun

doi:10.1016/j.bmc.2021.116350

Cited by 6 publications

(3 citation statements)

References 33 publications

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“…The N -acylsulfonamide moiety appears in an increasing number of pharmaceutical compounds for a wide range of therapeutic applications. 1–6 Characterized by an additional carbonyl group that could increase binding interactions compared to its sulfonamide parent, the N -acylsulfonamide group has also been used as a surrogate for carboxylic acids and phosphates. 7–9 The particular physico-chemical properties of the N -acylsulfonamide functionality are evidenced by the significant presence of this moiety in a wide variety of enzyme inhibitors such as methionyl-tRNA synthetase (MetRS), 10 asparagine synthetase (AS), 11,12 anthranilyl-CoA synthetase, 13 pantothenate synthetase 14 or carbonic anhydrases (Fig.…”

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confidence: 99%

Facile access to 4′-(N-acylsulfonamide) modified nucleosides and evaluation of their inhibitory activity against SARS-CoV-2 RNA cap N7-guanine-methyltransferase nsp14

et al. 2022

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confidence: 99%

Facile access to 4′-(N-acylsulfonamide) modified nucleosides and evaluation of their inhibitory activity against SARS-CoV-2 RNA cap N7-guanine-methyltransferase nsp14

et al. 2022

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“…the "privileged scaffold" concept). [14][15][16] This is attested by the rising number of drugs and lead molecules comprising an N-acylsulfonamide moiety recently identified showing biological activity against various targets such as voltage-gated sodium channels for pain treatment 17,18 or Bcl-2 19 and MMP2 20 protein targets for cancer therapy. Moreover, N-acylsulfonamide derivatives arouse specific interest as bioisosteres of carboxylic acid compounds.…”

Section: Introductionmentioning

confidence: 99%

N-Acylsulfonamide: a valuable moiety to design new sulfa drug analogues

et al. 2023

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“…Many compounds have been designed, synthesized, and evaluated as inhibitors of these target proteins. ABT-199 and derivatives with an acyl sulfonamide skeleton were shown to have antiproliferative effects targeting Bcl-2 ( Wang et al, 2021 ). Bortezomib, carfilzomib, and syringolin analogs have demonstrated potential antitumor activity targeting PSMB5 ( Yoshida et al, 2018 ; Allmeroth et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Discovery of Ligustrazine–Heterocycle Derivatives as Antitumor Agents

Zhang

Hou

et al. 2022

Front. Chem.

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Ligustrazine (TMP) is a natural pyrazine alkaloid extracted from the roots of Ligusticum Chuanxiong Hort, which has the potential as an antitumor agent. A series of 33 ligustrazine–heterocycle (TMPH) derivatives were designed, synthesized, and investigated via antitumor screening assays, molecular docking analysis, and prediction of drug-like properties. TMP was attached to other heterocyclic derivatives by an 8–12 methylene alkyl chain as a linker to obtain 33 TMPH derivatives. The structures were confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectroscopy spectral (HR-MS) data. The antiproliferative activity against human breast cancer MCF-7, MDA-MB-231, mouse breast cancer 4T1, mouse fibroblast L929, and human umbilical vein endothelial HUVEC cell lines was evaluated by MTT assay. Compound 12–9 displayed significant inhibitory activity with IC50 values in the low micromolar range (0.84 ± 0.02 µM against the MDA-MB-231 cell line). The antitumor effects of compound 12–9 were further evaluated by plate cloning, Hoechst 33 342 staining, and annexin V-FITC/PI staining. The results indicated that compound 12–9 inhibited the proliferation and apoptosis of breast cancer cells. Furthermore, molecular docking of compound 12–9 into the active site of the Bcl-2, CASP-3, and PSMB5 target proteins was performed to explore the probable binding mode. The 33 newly synthesized compounds were predicted to have good drug-like properties in a theoretical study. Overall, these results indicated that compound 12–9 inhibited cell proliferation through PSMB5 and apoptosis through Bcl-2/CASP-3 apoptotic signaling pathways and had good drug-like properties. These results provided more information, and key precursor lead derivatives, in the search for effective bioactive components from Chinese natural medicines.

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Discovery of potent and selective Bcl-2 inhibitors with acyl sulfonamide skeleton

Cited by 6 publications

References 33 publications

Facile access to 4′-(N-acylsulfonamide) modified nucleosides and evaluation of their inhibitory activity against SARS-CoV-2 RNA cap N7-guanine-methyltransferase nsp14

Facile access to 4′-(N-acylsulfonamide) modified nucleosides and evaluation of their inhibitory activity against SARS-CoV-2 RNA cap N7-guanine-methyltransferase nsp14

N-Acylsulfonamide: a valuable moiety to design new sulfa drug analogues

Synthesis and Discovery of Ligustrazine–Heterocycle Derivatives as Antitumor Agents

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