Structure-based identification of novel sirtuin inhibitors against triple negative breast cancer: An in silico and in vitro study

Sinha, Sonam; Patel, Shivani; Athar, Mohd; Vora, Jaykant; Chhabria, Mahesh T.; Jha, Prakash C.; Shrivastava, Neeta

doi:10.1016/j.ijbiomac.2019.08.061

Cited by 27 publications

(18 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to the RMSD of the ligand-bound structures, the dynamic stability was achieved at 20 ns. Furthermore, Sinha and coworkers [90] studied the stability of sirtuin-inhibitor complexes with the high-speed simulation software Desmond [91] employing the OPLS2005 [17] force field. After carrying out a virtual screening of plant-derived compounds against SIRT1-7 by docking and scoring, they identified sulforaphane, kaempferol, and apigenin as hits.…”

Section: Ligand-binding Dynamics Of Sirtuins-in Search Of Therapeuticmentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

View full text Add to dashboard Cite

Molecular dynamics (MD) simulations have become increasingly useful in the modern drug development process. In this review, we give a broad overview of the current application possibilities of MD in drug discovery and pharmaceutical development. Starting from the target validation step of the drug development process, we give several examples of how MD studies can give important insights into the dynamics and function of identified drug targets such as sirtuins, RAS proteins, or intrinsically disordered proteins. The role of MD in antibody design is also reviewed. In the lead discovery and lead optimization phases, MD facilitates the evaluation of the binding energetics and kinetics of the ligand-receptor interactions, therefore guiding the choice of the best candidate molecules for further development. The importance of considering the biological lipid bilayer environment in the MD simulations of membrane proteins is also discussed, using G-protein coupled receptors and ion channels as well as the drug-metabolizing cytochrome P450 enzymes as relevant examples. Lastly, we discuss the emerging role of MD simulations in facilitating the pharmaceutical formulation development of drugs and candidate drugs. Specifically, we look at how MD can be used in studying the crystalline and amorphous solids, the stability of amorphous drug or drug-polymer formulations, and drug solubility. Moreover, since nanoparticle drug formulations are of great interest in the field of drug delivery research, different applications of nano-particle simulations are also briefly summarized using multiple recent studies as examples. In the future, the role of MD simulations in facilitating the drug development process is likely to grow substantially with the increasing computer power and advancements in the development of force fields and enhanced MD methodologies.

show abstract

Section: Ligand-binding Dynamics Of Sirtuins-in Search Of Therapeuticmentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Furthermore, to regulate TNFα and IL-6 production, apigenin seems to exert its anticancer activity also by decreasing expression of histone deacetylase, SIRT6, in a dose-dependent manner. This results in a minor viability of cells and a decrease of colony forming capacity [110]. Moreover, apigenin is able to reduce the inflammation effects of cigarette smoke, reducing ROS production by a mechanism that involves a decreased expression of miR-21, an onco-miRNA overexpressed in different types of cancer, and interleukin-8, a proinflammatory cytokine [111].…”

Section: Apigeninmentioning

confidence: 99%

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

Barreca

Mandalari

Calderaro

et al. 2020

Plants

101

View full text Add to dashboard Cite

Citrus spp. are among the most widespread plants cultivated worldwide and every year millions of tons of fruit, juices, or processed compounds are produced and consumed, representing one of the main sources of nutrients in human diet. Among these, the flavonoids play a key role in providing a wide range of health beneficial effects. Apigenin, diosmetin, luteolin, acacetin, chrysoeriol, and their respective glycosides, that occur in concentrations up to 60 mg/L, are the most common flavones found in Citrus fruits and juices. The unique characteristics of their basic skeleton and the nature and position of the substituents have attracted and stimulated vigorous investigations as a consequence of an enormous biological potential, that manifests itself as (among other properties) antioxidant, anti-inflammatory, antiviral, antimicrobial, and anticancer activities. This review analyzes the biochemical, pharmacological, and biological properties of Citrus flavones, emphasizing their occurrence in Citrus spp. fruits and juices, on their bioavailability, and their ability to modulate signal cascades and key metabolic enzymes both in vitro and in vivo. Electronic databases including PubMed, Scopus, Web of Science, and SciFinder were used to investigate recent published articles on Citrus spp. in terms of components and bioactivity potentials.

show abstract

“…Natural polyphenol analogues (Figure 7) were identified as either SIRT6 activators or inhibitors 300,308–312 . There are three structural features that distinct some of them as potent inhibitors.…”

Section: Sirt6 Modulatorsmentioning

confidence: 99%

Emerging roles of SIRT6 in human diseases and its modulators

Liu

Chen

Liu

et al. 2020

Medicinal Research Reviews

103

View full text Add to dashboard Cite

The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty‐acylation, and mono‐ADP‐ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life‐threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases including cancer, inflammation, diabetes, steatohepatitis, arthritis, cardiovascular diseases, neurodegenerative diseases, viral infections, renal and corneal injuries, as well as the elucidation of the related signaling pathways. Moreover, we discuss the advances in the development of small molecule SIRT6 modulators including activators and inhibitors as well as their pharmacological profiles toward potential therapeutics for SIRT6‐mediated diseases.

show abstract

Structure-based identification of novel sirtuin inhibitors against triple negative breast cancer: An in silico and in vitro study

Cited by 27 publications

References 51 publications

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

Emerging roles of SIRT6 in human diseases and its modulators

Contact Info

Product

Resources

About