Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity

Ni, Jingxuan; Guo, Mengye; Cao, Yucheng; Lei, Lei; Liu, Kangli; Wang, Binghua; Lu, Fangfang; Zhai, R. Grace; Gao, Xiangwei; Yan, Chunhong; Wang, Hongbo; Bi, Yi

doi:10.1016/j.ejmech.2018.10.059

Cited by 26 publications

(12 citation statements)

References 18 publications

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“…Although fusidic acid did not enhance the cytotoxicity of HB21-LR at the concentrations we tested, the low concentration required to diminish cell viability suggests that higher doses might be worth evaluating. Recent studies have suggested that fusidic acid, and derivatives thereof, may have therapeutic utility for the treatment of cancers [27, 28]. We conclude that further investigation into synergy between the six antibiotics evaluated and RITs is not warranted, but it may be useful to explore fusidic acid alone as a treatment for cancer.…”

Section: Discussionmentioning

confidence: 89%

Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture

Zhu

Weldon

2019

BMC Res Notes

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Objective Recombinant immunotoxins (RITs) are antibody-toxin fusion proteins that can selectively eliminate populations of cells expressing specific surface receptors. They are in evaluation as therapeutic agents for cancer. RITs based on Pseudomonas exotoxin A (PE) are in use clinically for the treatment of hairy cell leukemia, and under trial for the treatment of other cancers. In an effort to improve the efficacy of PE-based RITs, we evaluated the potential of combination therapy with several common antibiotics (tetracycline, chloramphenicol, streptomycin, linezolid, fusidic acid, and kanamycin) on human cell lines HEK293, OVCAR8, and CA46. Antibiotics were selected based on their potential to inhibit mitochondrial protein synthesis and disrupt energy metabolism in cancer cells. Results Tetracycline, chloramphenicol, linezolid, and fusidic acid alone killed cultured human cells at high concentrations. At high but nontoxic concentrations of each antibiotic, only chloramphenicol treatment of the Burkitt’s lymphoma cell line CA46 showed enhanced cytotoxicity when paired with an anti-transferrin receptor/PE RIT. This result, however, could not be replicated in additional Burkitt’s lymphoma cell lines Ramos and Raji. Although the six antibiotics we tested are not promising candidates for RIT combination therapy, we suggest that fusidic acid could be considered independently as a potential cancer therapeutic. Electronic supplementary material The online version of this article (10.1186/s13104-019-4337-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 89%

Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture

Zhu

Weldon

2019

BMC Res Notes

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“…Fusidic acid (FA, 2) is a triterpene acid that belongs to the family of tetracyclic fusidane nor-triterpenes and has been clinically employed as an antibiotic for staphylococcal infections [18]. Additionally, it has been reported that fusidic acid sodium salt, an approved bacteriostatic antibiotic, showed significant cytotoxic effects (in vitro and in vivo) towards various colon cancer cells alone or coupled with 5-fluorouracil [19,20]. Moreover, various studies have been reported that cholic acid (CA, 3), which is steroidal acid, can be used for the prevention and treatment of colon cancer [21,22].…”

Section: Introductionmentioning

confidence: 99%

Access to New Cytotoxic Triterpene and Steroidal Acid-TEMPO Conjugates by Ugi Multicomponent-Reactions

Sultani

Morgan

Hussain

et al. 2021

IJMS

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Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic acid (FA), cholic acid (CA) conjugates with TEMPO (nitroxide) have been prepared using this approach, which also makes them applicable in electron paramagnetic resonance (EPR) spectroscopy. Moreover, convertible amide modified spin-labelled fusidic acid derivatives were selected for post-Ugi modification utilizing a wide range of reaction conditions which kept the paramagnetic center intact. The nitroxide labelled betulinic acid analogue 6 possesses cytotoxic effects towards two investigated cell lines: prostate cancer PC3 (IC50 7.4 ± 0.7 μM) and colon cancer HT29 (IC50 9.0 ± 0.4 μM). Notably, spin-labelled fusidic acid derivative 8 acts strongly against these two cancer cell lines (PC3: IC50 6.0 ± 1.1 μM; HT29: IC50 7.4 ± 0.6 μM). Additionally, another fusidic acid analogue 9 was also found to be active towards HT29 with IC50 7.0 ± 0.3 μM (CV). Studies on the mode of action revealed that compound 8 increased the level of caspase-3 significantly which clearly indicates induction of apoptosis by activation of the caspase pathway. Furthermore, the exclusive mitochondria targeting of compound 18 was successfully achieved, since mitochondria are the major source of ROS generation.

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“…[8] Since the discovery of this natural molecule, many analogs of FA with antibacterial properties have been obtained. [9][10][11][12][13] In addition, their antiparasitic, [14] anti-inflammatory, [15] antiviral, [16] antimalarial, [17] and antitumor [18] effects have been shown. The global problem of antibacterial resistance currently has led to renewed interest in the design and synthesis of new FA analogs with a longer period of resistance development and a wide range of pharmacological actions.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Activity of Oximes, Amines, and Lactams of Fusidane Triterpenoids

Салимова

Parfenova

2021

ChemistrySelect

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The article presents the synthesis and study of the antimicrobial and antitumor activity of fusidic acid derivatives containing oxime, amino substituents, and a caprolactam ring. The introduction of a caprolactam fragment into the molecule provides a high antibacterial effect comparable to that of fusidic acid and contributes to a 5.8-fold decrease in hemolytic activity compared to that of the native antibiotic. The presence of two oxime groups in the methylfusidate molecule ensures a high antiproliferative effect against H522 cells of non-small cell lung cancer, leading to 57 % of the lethality of this cell line.

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Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity

Cited by 26 publications

References 18 publications

Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture

Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture

Access to New Cytotoxic Triterpene and Steroidal Acid-TEMPO Conjugates by Ugi Multicomponent-Reactions

Synthesis and Biological Activity of Oximes, Amines, and Lactams of Fusidane Triterpenoids

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