Ginsengenin derivatives synthesized from 20(R)-panaxotriol: Synthesis, characterization, and antitumor activity targeting HIF-1 pathway

Guo, Hongyan; Xing, Yue; Sun, Yu-Qiao; Liu, Can; Xu, Qian; Shang, Fan-Fan; Zhang, Runhui; Jin, Xuejun; Chen, Fen‐Er; Lee, Jun Young; Dong-zhou, Kang; Shen, Qing-Kun; Quan, Zhe‐Shan

doi:10.1016/j.jgr.2022.03.001

Cited by 11 publications

(3 citation statements)

References 52 publications

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“…Cinnamic acid, , pyridine/furan , and triazolyl moieties have been considered common structures in the design of anticancer drugs due to their dipolar interaction, hydrogen bond formation ability, rigidity, and solubility. , For instance, cinnamic acid was presented in many active molecules with good efficacy, such as (−)-Englerin A ( 12 ), which has been under intensive preclinical investigation at the NCI . Orelabrutinib ( 13 ) and zytiga ( 14 ) containing a pyridine moiety have been approved for listing by the FDA. , In addition, the triazolyl group has been successfully applied in the development of selinexor ( 15 ), letrozole ( 16 ), and talzenna ( 17 ). , Furan and thiophene were used to develop tykerb ( 18 ) and orgovyx ( 19 ). , These drugs can be used effectively in cancer treatment (Figure ).…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, suitable modifications of 2-OH and 16-OH could improve the antitumor activity and reduce the toxicity of CuB. Cinnamic acid, 14,15 pyridine/furan 16,17 and triazolyl moieties have been considered common structures in the design of anticancer drugs due to their dipolar interaction, hydrogen bond formation ability, rigidity, and solubility. 18,19 For instance, cinnamic acid was presented in many active molecules with good efficacy, such as (−)-Englerin A (12), which has been under intensive preclinical investigation at the NCI.…”

Section: ■ Introductionmentioning

confidence: 99%

“…18,19 For instance, cinnamic acid was presented in many active molecules with good efficacy, such as (−)-Englerin A (12), which has been under intensive preclinical investigation at the NCI. 20 Orelabrutinib (13) and zytiga (14) containing a pyridine moiety have been approved for listing by the FDA. 21,22 In addition, the triazolyl group has been successfully applied in the development of selinexor (15), letrozole (16), and talzenna (17).…”

Section: ■ Introductionmentioning

confidence: 99%

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Discovery of Triazolyl Derivatives of Cucurbitacin B Targeting IGF2BP1 against Non-Small Cell Lung Cancer

Shang,

Lu,

Lin

et al. 2023

J. Med. Chem.

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Cucurbitacin B (CuB) is a potent but toxic anticancer natural product. Herein, we designed and synthesized 2-OH-and 16-OH-modified CuB derivatives to improve their antitumor efficacy and reduce toxicity. Among them, derivative A11 had the most potent antiproliferative activity against A549 lung cancer cells (IC 50 = 0.009 μM) and was approximately 10-fold more potent than CuB, while the cytotoxicity of A11 toward normal L02 cells was about 10-fold less potent, indicating a much wider therapeutic window than CuB. Derivative A11 directly binds to the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) protein with a K D value of 2.88 nM, which is about 23fold more potent than CuB, leading to the decreased expression of downstream apoptosis-and cell cycle-related proteins. More importantly, A11 exhibited much more potent anticancer efficacy in an A549 xenograft mouse model with a TGI rate of 80% and a superior in vivo safety profile than that of CuB.

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