Design, synthesis and tumor cell growth inhibitory activity of 3-nitro-2 H -cheromene derivatives as histone deacetylaes inhibitors

Tan, Shuai; He, Feng; Kong, Tingting; Wu, Jingde; Liu, Zhaopeng

doi:10.1016/j.bmc.2017.05.062

Cited by 17 publications

(12 citation statements)

References 22 publications

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“…As expected, the amine anchor shows a threefold lower deviation in distance across compared crystal structures in contrast to the to the second heteroatom with a wide range of distances between 2.5 Å and 2.7 Å. Interactions generated by the cap and linker group are of diverse origin and tune the selectivity, potency, pharmacokinetic properties, and toxicity, contributing to the overall pharmacological performance of the inhibitor. The structure–activity relationship (SAR) below is suggested for classic amino benzamide warheads on the basis of the work of Li et al [ 79 ], Tan et al [ 80 ], Chen et al [ 81 ], Bressi et al [ 77 ], and Lauffer et al [ 30 ] ( Figure 6 ).…”

Section: Classic Benzamide Warheadsmentioning

confidence: 99%

“…Further modification of the ZBG of 3–5 yielded derivatives b–d . Tan et al [ 80 ] prepared several ZBGs with 3-nitro-2 H -chromene derivatives as cap moieties. Amino benzamide compounds 6a and 7a preferentially inhibited HDAC1 over HDAC2 with IC 50 values of 128 nM and 179 nM for HDAC1 and 659 nM and 827 nM for HDAC2, being more potent than the reference compound entinostat.…”

Section: Classic Benzamide Warheadsmentioning

confidence: 99%

“…Monodentate species such as 41 and 42 are also potent inhibitors with activity in the nM range [ 101 , 103 ]. Compounds 43–45 exhibited poor potency against the tested HDAC1, HDAC2, and HDAC6 isoforms, but had better antiproliferative activities than the amino benzamide and α-amino amide ZBGs, suggesting additional mechanisms of action [ 80 ]. The canonical binding pocket of HDAC8 is highly moldable, allowing for the accommodation of small structures such as SAHA and sterically demanding moieties such as 35 ( Figure 11 A,B).…”

Section: Amide Warheadsmentioning

confidence: 99%

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Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Frühauf

Meyer‐Almes

2021

Molecules

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Histone deacetylases (HDACs) remove acetyl groups from acetylated lysine residues and have a large variety of substrates and interaction partners. Therefore, it is not surprising that HDACs are involved in many diseases. Most inhibitors of zinc-dependent HDACs (HDACis) including approved drugs contain a hydroxamate as a zinc-binding group (ZBG), which is by far the biggest contributor to affinity, while chemical variation of the residual molecule is exploited to create more or less selectivity against HDAC isozymes or other metalloproteins. Hydroxamates have a propensity for nonspecificity and have recently come under considerable suspicion because of potential mutagenicity. Therefore, there are significant concerns when applying hydroxamate-containing compounds as therapeutics in chronic diseases beyond oncology due to unwanted toxic side effects. In the last years, several alternative ZBGs have been developed, which can replace the critical hydroxamate group in HDACis, while preserving high potency. Moreover, these compounds can be developed into highly selective inhibitors. This review aims at providing an overview of the progress in the field of non-hydroxamic HDACis in the time period from 2015 to present. Formally, ZBGs are clustered according to their binding mode and structural similarity to provide qualitative assessments and predictions based on available structural information.

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Section: Classic Benzamide Warheadsmentioning

confidence: 99%

Section: Classic Benzamide Warheadsmentioning

confidence: 99%

Section: Amide Warheadsmentioning

confidence: 99%

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Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Frühauf

Meyer‐Almes

2021

Molecules

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“…Tan et al [44] synthesized and investigated a series of 8-ethoxy-3nitro-2H-chromene based HDACIs against K562, A549, MCF-7, PC3, and HeLa cancer cell lines. The research revealed that o-amino anilide and D-Phe substituted α-amino amide derivatives (16a and 16b) were more effective toward HADC1 over HADC2 and were moderated to weak active over HADC6.…”

Section: Anticancer Activitymentioning

confidence: 99%

Coumarins: A Unique Scaffold With Versatile Biological Behavior

Gupta¹,

Kumar²,

Chaudhary³

2019

Asian J Pharm Clin Res

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Benzopyrones are the club of compounds that can be coumarins or flavonoids. The hydroxyl derivatives of coumarins such as 4-hydroxycoumarins and 7-hydroxycoumarins have extensive biological activities which have employed for the synthesis of miscellaneous coumarin derivatives. These derivatives have exhibited impressive pharmacological and physiological activities such as anticoagulant, antibacterial, antiviral, antitumor, bactericidal, fungicidal, anti-inflammatory agents, and anti-HIV activity. This review comprised pharmacokinetic studies, including absorption, distribution, and metabolism of coumarin analogs along with toxicological studies. The studies of coumarins and their derivatives exhibiting immense pharmacological activity are also summarized in the current study.

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“…Natural, semi-synthetic and synthetic coumarins are useful substances in drug research. Coumarins can be used not only to treat cancer, but also to treat the side effects caused by radiotherapy ( 16 – 18 ). In this paper, series of coumarin derivatives [I (a–d) and II (a–d)] ( Figure 1 ) have been synthesized and their potential antitumor activity was investigated.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of coumarin derivatives against human lung cancer cell lines

Weng

Yuan

2017

Braz J Med Biol Res

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Series of novel coumarin derivatives [I (a–d) and II (a–d)] were successfully synthesized and their structures were determined based on infrared 1H-nuclear magnetic resonance (NMR), HRMS, and single crystal X-ray crystallography. Additionally, the new synthesized compounds were evaluated to identify the molecular characteristics that contribute to their cytotoxicity, which was tested against SK-LU-1, SPC-A-1 and 95D human lung cancer cell lines, using the MTT assay. The results of this study showed that compounds Ic, Id, IIc, and IId exhibited an efficient percentage of inhibition of cell proliferation.

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Design, synthesis and tumor cell growth inhibitory activity of 3-nitro-2 H -cheromene derivatives as histone deacetylaes inhibitors

Cited by 17 publications

References 22 publications

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Coumarins: A Unique Scaffold With Versatile Biological Behavior

Synthesis and evaluation of coumarin derivatives against human lung cancer cell lines

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