Synthesis of nοvel artemisinin dimers with polyamine linkers and evaluation of their potential as anticancer agents

Magoulas, George E.; Τσίγκου, Τζοάννα; Skondra, Lina; Lamprou, Margarita; Τσουκαλά, Παναγιώτα; Kokkinogouli, Vassiliki; Pantazaka, Evangelia; Papaioannou, Dionissios; Athanassopoulos, Constantinos M.; Papadimitriou, Evangelia

doi:10.1016/j.bmc.2017.05.018

Cited by 18 publications

(10 citation statements)

References 52 publications

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“…A mitochondrial-targeting analog of ART is also synthesized to specifically target mitochondria for enhancing the inhibition of cell proliferation in various cancer cells including HCT-116, MDA-MB-231, HeLa and SKBR3 cells [211]. Moreover, dimmers of ART are also synthesized by polyamine linkers, and they further inhibit cell proliferation in human breast cancer MCF-7 cells and angiogenesis in HUVECs [212].…”

Section: Artemisininsmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Section: Artemisininsmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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“…25 An alternative synthesis of this key-intermediate has been described. 15 Finally for the needs of the present work, the N 1 -(7-chloroquinolin-4-yl)ethane-1,2-diamine (15) and the 7-chloro-4-(piperazin-1-yl)quinoline ( 16) were readily obtained in 56% and 76% yield, respectively, from the commercially available 4,7-dichloroquinoline through the nucleophilic aromatic substitution of the latter with 1,2-diaminoethane and piperazine, respectively 17 ditritylhomospermidine (19). These compounds are readily available, in 48% overall yield, from butane-1,4-diamine (putrescine, Put) through a three-steps sequence depicted in Scheme S1 (Supporting Information).…”

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confidence: 78%

“…1 Examples of ART-CQ (S1-S2) 1,11 or a G-factor-CQ (S3) hybrids, 11 and of conjugates (S4-S7) of ART with the naturally occurring polyamines (PAs), e.g. spermidine (Spd) or spermine (Spm), [18][19][20] of relevance to the present work are provided in Figure S1 (Supporting Information). It should be noted that naturally occurring and synthetic PAs, their analogs and conjugates with other biologically active molecules are compounds with a variety of interesting biological properties.…”

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confidence: 99%

Synthesis of Novel G Factor or Chloroquine-Artemisinin Hybrids and Conjugates with Potent Antiplasmodial Activity

Pepe

Toumpa

André-Barrès

et al. 2020

ACS Med. Chem. Lett.

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A series of novel hybrids of artemisinin (ART) with either a phytormone endoperoxide G factor analogue (GMeP) or chloroquine (CQ) and conjugates of the same compounds with the polyamines (PAs) spermidine (Spd) and homospermidine (Hsd) were synthesized and their antimalarial activity were evaluated using the CQ-resistant P. falciparum FcB1/Colombia strain. The ART-GMeP hybrid 5 and compounds 9 and 10 which are conjugates of Spd and Hsd with two molecules of ART, and one molecule of GMeP, were the most potent with IC50 values of 2.6, 8.4 and 10.6 nM, respectively. The same compounds also presented the highest selectivity indexes against the primary human fibroblast cell line AB943 ranging from 16,372 for the hybrid 5 to 983 for the conjugate 10 of Hsd.

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“…Cumulative studies revealed that nanoliposomal formulation of artemisinins substantially increased the antitumor effects of artemisinin-related compounds. Despite of nanoliposomal artemisinins, researches also focus on the development of novel artemisinin-based compounds with anti-breast cancer properties [ 80 ]. A hybrid compound tethering DHA with diaryl-pyrazoline through ether linkage was found to exhibit potent activity in three breast cancer cell lines including MCF-7/Adr (GI 50 = 18 nM), MCF-7 (GI 50 = 210 nM) and MDA-MB-231 (GI 50 = 210 nM) [ 81 ].…”

Section: Antitumor Activity Of Artemisininmentioning

confidence: 99%

Antitumor Research on Artemisinin and Its Bioactive Derivatives

Zhang

et al. 2018

Nat. Prod. Bioprospect.

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Cancer is the leading cause of human death which seriously threatens human life. The antimalarial drug artemisinin and its derivatives have been discovered with considerable anticancer properties. Simultaneously, a variety of target-selective artemisinin-related compounds with high efficiency have been discovered. Many researches indicated that artemisinin-related compounds have cytotoxic effects against a variety of cancer cells through pleiotropic effects, including inhibiting the proliferation of tumor cells, promoting apoptosis, inducing cell cycle arrest, disrupting cancer invasion and metastasis, preventing angiogenesis, mediating the tumor-related signaling pathways, and regulating tumor microenvironment. More importantly, artemisinins demonstrated minor side effects to normal cells and manifested the ability to overcome multidrug-resistance which is widely observed in cancer patients. Therefore, we concentrated on the new advances and development of artemisinin and its derivatives as potential antitumor agents in recent 5 years. It is our hope that this review could be helpful for further exploration of novel artemisinin-related antitumor agents.Graphical Abstract

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Synthesis of nοvel artemisinin dimers with polyamine linkers and evaluation of their potential as anticancer agents

Cited by 18 publications

References 52 publications

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Synthesis of Novel G Factor or Chloroquine-Artemisinin Hybrids and Conjugates with Potent Antiplasmodial Activity

Antitumor Research on Artemisinin and Its Bioactive Derivatives

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