Design, synthesis and biological evaluation of novel hydroxamic acids bearing artemisinin skeleton

Hà, Vũ Thị Thu; Kien, Vu Tuan; Binh, Le Huy; Tien, Vu Dinh; My, Nguyen Thi Thuy; Nam, Nguyen Hai; Baltas, Michel; Hahn, Hyunggu; Han, Byung Woo; Thao, Do Thi; Vu, Tran Khac

doi:10.1016/j.bioorg.2016.03.008

Cited by 22 publications

(5 citation statements)

References 33 publications

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“…Amongst them, only two compounds 70(a), and 70(b), showed excellent HDAC (histone deacetylases) selectivity with IC 50 values of 29.31 and 22.7 µM, respectively. The structure of a hydroxamic acid artemisinin hybrid is shown in Figure 67 and the in vitro cytotoxic activities of hybrid compounds 70(a-c) are listed in Table 55 [136]. The structure of novel hydroxamate-β-carboline based derivatives is given in Figure 68 and the in vitro cytotoxic activities of hybrid compounds 71(a-d) are listed in Table 56 [137].…”

Section: Hydroxamic Acid Hybridsmentioning

confidence: 99%

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

et al. 2022

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Cancer is a complex disease, and its treatment is a big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach is a potential strategy in recent drug discovery that involves the combination of two drug pharmacophores into a single molecule. The hybrid molecule acts through distinct modes of action on several targets at a given time with more efficacy and less susceptibility to resistance. Thus, there is a huge scope for using hybrid compounds to tackle the present difficulties in cancer medicine. Recent work has applied this technique to uncover some interesting molecules with substantial anticancer properties. In this study, we report data on numerous promising hybrid anti-proliferative/anti-tumor agents developed over the previous 10 years (2011–2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, and pyridine-based anticancer hybrids produced via molecular hybridization techniques. Overall, this review offers a clear indication of the potential benefits of merging pharmacophoric subunits from multiple different known chemical prototypes to produce more potent and precise hybrid compounds. This provides valuable knowledge for researchers working on complex diseases such as cancer.

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Section: Hydroxamic Acid Hybridsmentioning

confidence: 99%

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

et al. 2022

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“…In the past years, numerous artemisinin-derived hybrids have been synthesized and investigated for their biological activity [ 22 , 23 ]. However, only one report on artemisinin–HDACi hybrids have been published so far, and to the best of our knowledge, none of the compounds was tested for its antiplasmodial properties [ 24 ]. In this study, we present the synthesis and biological evaluation of newly designed dihydroartemisinin-based HDACi hybrid drugs.…”

Section: Introductionmentioning

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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“…Fascinatingly, hybrid molecules consisting of heterocyclic compounds and natural products created new biological activities, or enhance the current bio-logical activities. [18] For example, artemisinin and chloroquine are used to treat the malaria. Pepe et al was synthesized artemisinin-chloroquine hybrid structures, then they reported that new hybrid molecule effectively increased the activity than both these antiviral drugs.…”

Section: Introductionmentioning

confidence: 99%

“…It was improved that heterocyclic compounds like thiophenes, furans, benzothiophenes, carbazoles are very important roles in medicinal chemistry and material science. Fascinatingly, hybrid molecules consisting of heterocyclic compounds and natural products created new biological activities, or enhance the current biological activities [18] . For example, artemisinin and chloroquine are used to treat the malaria.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Thiophene/Furan‐Artemisinin Hybrid Molecules

Ozok-Arici

Kavak

Kıvrak

2022

Chemistry & Biodiversity

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Natural products with semi-synthetic molecules displays higher biological activities, and creates new biological properties for the treatment of diseases. Although, natural products like artemisinin have been used as a traditional medicine over thousands of years, structure and biological properties of many natural products were investigated in the 20th century. Design and synthesis of new biologically active compounds including natural products have very critical roles to find novel drug candidates. Herein, novel thiophene/furan bridge artemisinin derivatives were synthesized by starting from artemisinin. Firstly, benzothiophene derivatives are synthesized, then Steglich esterification reactions give the new artemisinin hybrid molecules with moderate to high yields.

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Design, synthesis and biological evaluation of novel hydroxamic acids bearing artemisinin skeleton

Cited by 22 publications

References 33 publications

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

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

Synthesis of Thiophene/Furan‐Artemisinin Hybrid Molecules

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