Synthesis, Biological Evaluation, and Computer‐Aided Drug Designing of New Derivatives of Hyperactive Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitors

Zhang, Song; Huang, Weibin; Li, Xiaonan; Yang, Zhicheng; Feng, Bin

doi:10.1111/cbdd.12554

Cited by 10 publications

(3 citation statements)

References 24 publications

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“…102 In one of the reported studies, the estimated binding free energy of SAHA for HDAC8 was calculated as −4.35 kcal/mol. 103 Docking score of SAHA against HDAC2 was found as −7.068 kcal/mol by MOE software. 104 Furthermore, in one of the reported studies, SAHA was compared with naturally occurring components including apigenin, flavone, and luteolin against HDAC1 and HDAC2.…”

Section: In Silico Studiesmentioning

confidence: 99%

**Major Bioactive Prenylated Flavonoids from Humulus lupulus L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review**

Comert Onder,

Kalin,

Sahin

et al. 2023

Pharm Sci

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In recent years, the incidence of cancers, inflammatory diseases, Alzheimer’s disease, glucose metabolism disorder and diabetes has increased alarmingly which demands more research into the discovery of new drug candidates to treat these human diseases. Main phytochemicals from Humulus lupulus L. (hops) have been demonstrated to have positive impacts on human health, and prenylated flavonoids are one of the major groups of bioactive phytochemicals found in this plant. Thus, this review summarizes the role of major prenylated components in hops in human diseases including cancer, inflammation and viral infections. In silico studies of prenylated bioactive compounds against various drug targets such as histone deactylases (HDACs), sirtuins (SIRTs), and acetylcholinesterase (AChE), and the molecular molecular interactions between protein and ligand have also been included. Furthermore, the structure-activity relationships (SAR) studies on these compounds are highlighted. This review concludes that the prenylated phytochemicals from H. lupulus L., including xanthohumol (XN), isoxanthohumol (IXN), 8-prenylnaringenin (8-PN) and 6-prenylnaringenin (6-PN), have promising roles in human health and may contribute to new drug discovery and development.

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Section: In Silico Studiesmentioning

confidence: 99%

**Major Bioactive Prenylated Flavonoids from Humulus lupulus L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review**

Comert Onder,

Kalin,

Sahin

et al. 2023

Pharm Sci

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“…Zhang et al 58 outlined the synthesis, characterization, and biological evaluation of suberoylanilide hydroxamic acid (SAHA)-based derivatives with greater binding towards HDAC8 than the SAHA. Compound 2 shows pronounced activity while inhibiting the cancerous cell lines of human glioma, i.e., MGR2, U251, and U373.…”

Section: (1)mentioning

confidence: 99%

Histone Deacetylase Inhibitors: A Prospect in Drug Discovery

Yadav¹,

Mishra²,

Yadav³

2019

tjps

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Kanser tedavisi tüm toplum için büyük bir kışkırtıcıdır ve ilaç keşfi alanında bir araştırma hattını izlemektedir. Bu nedenle, işlemeyen ilaç hedeflerini iyileştirme yeterliliğine sahip, tıbbi aktif bir ajan keşfetmek için hayati bir gereklilik vardır. Artan pragmatik kanıtlar, histon deasetilazların (HDAC) kanserin ilerleme aşamasında deasetilasyonu arttırarak ve malignite değişikliklerini tetikleyerek kapana kısıldığını ifade etmektedir. HDAC inhibitörleri, ilaç keşfi bağlamında terapötik bir hedef olarak HDAC biyolojisiyle ilgili kimyasal varlığı araştırmak için, çığır açıcı iskele ve ulaşılabilir bir anahtar sağlarlar. HDAC inhibitörünün gen ekpresyonu yoluyla, kanserli hücrelere sitotoksisiteyi ihtiyatlı bir şekilde aktarmak için anti-kanser bir madde olarak geliştirilmesi yaklaşan bir gerekliliktir. Bu derlemede HDAC enziminin temelleri, inhibitörleri ve terapötik sonuçları üzerinde durulmuştur. Anahtar kelimeler: Histon deasetilaz inhibitörleri, apopitoz, çoklu tedavi yaklaşımı, kanser Cancer is a provocative issue across the globe and treatment of uncontrolled cell growth follows a deep investigation in the field of drug discovery. Therefore, there is a crucial requirement for discovering an ingenious medicinally active agent that can amend idle drug targets. Increasing pragmatic evidence implies that histone deacetylases (HDACs) are trapped during cancer progression, which increases deacetylation and triggers changes in malignancy. They provide a groundbreaking scaffold and an attainable key for investigating chemical entity pertinent to HDAC biology as a therapeutic target in the drug discovery context. Due to gene expression, an impending requirement to prudently transfer cytotoxicity to cancerous cells, HDAC inhibitors may be developed as anticancer agents. The present review focuses on the basics of HDAC enzymes, their inhibitors, and therapeutic outcomes.

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“…Histone deacetylases (HDACs) have been identified as attractive targets for cancer therapeutics, which are responsible for deacetylation of lysine resides in histone and non‐histone substrates (p53 and tubulin), and play important roles in regulating various tumor suppressor pathways . Until now, 18 human HDACs have been categorized into four classes: class I (HDAC1, 2, 3, and 8), class II (class IIa: HDAC4, 5, 7, and 9; class IIb: HDAC6, and 10), class III (sirtuins, and SIRT1‐7), and class IV (HDAC11) .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of quinazoline derivatives as dual HDAC1 and HDAC6 inhibitors for the treatment of cancer

et al. 2018

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Fifty‐eight quinazoline‐based compounds were designed and synthesized based on the structural optimizations from the lead compound 23bb in an attempt to search for more potent dual HDAC1 and HDAC6 inhibitors. Among them, 32c (HDAC1, IC50 = 31.10 ± 0.37 nM; HDAC6, IC50 = 16.15 ± 0.62 nM) and 32d (HDAC1, IC50 = 37.00 ± 0.24 nM; HDAC6, IC50 = 35.00 ± 0.71 nM) were not only identified as potent dual‐acting HDAC1 and HDAC6 inhibitors with over 10‐fold selectivity to the other HDACs, but also displayed activities in tubulin acetylation and histone H3 acetylation induction. Importantly, both of them displayed strong antiproliferative activities against various tumor cell lines in vitro with IC50 values less than 40 nM, especially for hematologic tumors cells (U266 and RPMI8226, IC50 < 1 nM), which were even better than 23bb and SAHA. Furthermore, 32c showed a significant tumor growth inhibition (antitumor rate = 63.98%, p < 0.05) in the resistant MCF‐7/ADR xenograft model without any obvious body weight changes and abnormal behaviors. Our findings validate that 32c is a potent dual inhibitor of HDAC1/6 that can be an efficacious treatment for breast cancer with Adriamycin resistance.

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Synthesis, Biological Evaluation, and Computer‐Aided Drug Designing of New Derivatives of Hyperactive Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitors

Cited by 10 publications

References 24 publications

**Major Bioactive Prenylated Flavonoids from Humulus lupulus L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review**

**Major Bioactive Prenylated Flavonoids from Humulus lupulus L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review**

Histone Deacetylase Inhibitors: A Prospect in Drug Discovery

Design, synthesis, and biological evaluation of quinazoline derivatives as dual HDAC1 and HDAC6 inhibitors for the treatment of cancer

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