Synthesis of novel S-linked dihydroartemisinin derivatives and evaluation of their anticancer activity

Gour, Rajesh; Ahmad, Fawad; Prajapati, Santosh Kumar; Giri, Santosh Kumar; Karna, Shibendra Kumar Lal; Kartha, K. P. Ravindranathan; Pokharel, Yuba Raj

doi:10.1016/j.ejmech.2019.06.018

Cited by 15 publications

(10 citation statements)

References 61 publications

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“…This enabled removal of the excess crystal violet. The six‐well plates were then inverted and the image of each well was photographed (Gour et al., 2019).…”

Section: Methodsmentioning

confidence: 99%

Anti‐inflammatory and anticancer activities of Naringenin‐loaded liquid crystalline nanoparticles in vitro

et al. 2020

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In this study, we had developed Naringenin-loaded liquid crystalline nanoparticles (LCNs) and investigated the anti-inflammatory and anticancer activities of Naringenin-LCNs against human airway epithelium-derived basal cells (BCi-NS1.1) and human lung epithelial carcinoma (A549) cell lines, respectively. The anti-inflammatory potential of Naringenin-LCNs evaluated by qPCR revealed a decreased expression of IL-6, IL-8, IL-1β, and TNF-α in lipopolysaccharide-induced BCi-NS1.1 cells. The activity of LCNs was comparable to the positive control drug Fluticasone propionate (10 nM). The anticancer activity was studied by evaluating the antiproliferative (MTT and trypan blue assays), antimigratory (scratch wound healing assay, modified Boyden chamber assay, and immunoblot), and anticolony formation activity in A549 cells. Naringenin LCNs showed promising antiproliferative, antimigratory, and anticolony formation activities in A549 cells, in vitro. Therefore, based on our observations and results, we conclude that Naringenin-LCNs may be employed as a potential therapy-based intervention to ameliorate airway inflammation and to inhibit the progression of lung cancer. Practical applications Naringenin was encapsulated into liquid crystalline nanoparticles, thus, attributing to their sustained-release nature. In addition, Naringenin-loaded LCNs efficiently reduced the levels of pro-inflammatory markers, namely, IL-1β, IL-6, TNF-α, and IL-8. In addition, the Naringenin-loaded LCNs also possess potent anticancer activity, when tested in the A549 cell line, as revealed by the inhibition of proliferation and migration of cells. They also attenuated colony formation and induced apoptosis in the A549 cells. The findings from our study could form the basis for future research that may be translated into an in vivo model to validate the possible therapeutic alternative for lung cancer using Naringenin-loaded LCNs. In addition, the applications of

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“…This enabled removal of the excess crystal violet. The six‐well plates were then inverted and the image of each well was photographed (Gour et al., 2019).…”

Section: Methodsmentioning

confidence: 99%

Anti‐inflammatory and anticancer activities of Naringenin‐loaded liquid crystalline nanoparticles in vitro

et al. 2020

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“…With the development of anti-tumor and inhibition of inflammation effects of DHA, in recent years, more and more studies have focused on how to improve the efficacy of DHA. The main strategies to enhance the efficacy of DHA include modifying the chemical structure of DHA (55), developing new DHA derivatives (134), building multimeric DHA conjugates (135), and coupling other drugs with DHA to achieve targeted tumor therapy (37,59,(136)(137)(138). Liu et al construct the R 8 modified epirubicindihydroartemisinin liposomes for the treatment of NSCLC, and find R 8 modified epirubicin-dihydroartemisinin liposomes have a stronger killing effect on A549 cells.…”

Section: Summary and Future Outlookmentioning

confidence: 99%

Dihydroartemisinin: A Potential Drug for the Treatment of Malignancies and Inflammatory Diseases

Jin

Fujimoto

2021

Front. Oncol.

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Dihydroartemisinin (DHA) has been globally recognized for its efficacy and safety in the clinical treatment of malaria for decades. Recently, it has been found that DHA inhibits malignant tumor growth and regulates immune system function in addition to anti-malaria. In parasites and tumors, DHA causes severe oxidative stress by inducing excessive reactive oxygen species production. DHA also kills tumor cells by inducing programmed cell death, blocking cell cycle and enhancing anti-tumor immunity. In addition, DHA inhibits inflammation by reducing the inflammatory cells infiltration and suppressing the production of pro-inflammatory cytokines. Further, genomics, proteomics, metabolomics and network pharmacology of DHA therapy provide the basis for elucidating the pharmacological effects of DHA. This review provides a summary of the recent research progress of DHA in anti-tumor, inhibition of inflammatory diseases and the relevant pharmacological mechanisms. With further research of DHA, it is likely that DHA will become an alternative therapy in the clinical treatment of malignant tumors and inflammatory diseases.

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“…The subsequent treatment of DHA with acetic anhydride provided the key intermediate dihydroartemisinin acetate ( 5 ). Following the procedure of Gour et al [ 27 ], 5 and the respective thiol or alcohol were subjected to a BF 3 -catalyzed reaction to generate the intermediates 6a–e . The hydroxamate-based target compounds were obtained in a two-step protocol.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin–HDAC Inhibitor Hybrids as Multitarget Drugs

et al. 2022

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Artemisinin-based combination therapies (ACTs) are the gold standard for the treatment of malaria, but the efficacy is threatened by the development of parasite resistance. Histone deacetylase inhibitors (HDACis) are an emerging new class of potential antiplasmodial drugs. In this work, we present the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin–HDACi hybrid molecules. The screening of the hybrid molecules for their activity against selected human HDAC isoforms, asexual blood stage P. falciparum parasites, and a panel of leukemia cell lines delivered important structure–activity relationships. All synthesized compounds demonstrated potent activity against the 3D7 and Dd2 line of P. falciparum with IC50 values in the single-digit nanomolar range. Furthermore, the hybrid (α)-7c displayed improved activity against artemisinin-resistant parasites compared to dihydroartemisinin. The screening of the compounds against five cell lines from different leukemia entities revealed that all hydroxamate-based hybrids (7a–e) and the ortho-aminoanilide 8 exceeded the antiproliferative activity of dihydroartemisinin in four out of five cell lines. Taken together, this series of hybrid molecules represents an excellent starting point toward the development of antimalarial and antileukemia drug leads.

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Synthesis of novel S-linked dihydroartemisinin derivatives and evaluation of their anticancer activity

Cited by 15 publications

References 61 publications

Anti‐inflammatory and anticancer activities of Naringenin‐loaded liquid crystalline nanoparticles in vitro

Anti‐inflammatory and anticancer activities of Naringenin‐loaded liquid crystalline nanoparticles in vitro

Dihydroartemisinin: A Potential Drug for the Treatment of Malignancies and Inflammatory Diseases

Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin–HDAC Inhibitor Hybrids as Multitarget Drugs

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