CoMFA, CoMSIA, Topomer CoMFA, HQSAR, molecular docking and molecular dynamics simulations study of triazine morpholino derivatives as mTOR inhibitors for the treatment of breast cancer

Chhatbar, Dhara M.; Chaube, Udit; Vyas, Vivek K.; Bhatt, Hardik

doi:10.1016/j.compbiolchem.2019.04.017

Cited by 33 publications

(6 citation statements)

References 30 publications

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“…Furthermore, a molecular docking study was performed to analyse the interactions of Scu with the active site of mTOR (Figure e,f). Homo sapiens mTOR (PDB ID: 4JT6) was chosen for the docking studies according to a previous report (Chhatbar, Chaube, Vyas, & Bhatt, ). Specifically, Scu is mainly incorporated into the active pocket of mTOR by hydrophobic interactions.…”

Section: Resultsmentioning

confidence: 99%

Scutellarin, a modulator of mTOR, attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP‐1c suppression

Luan

Huo

Zhao

et al. 2019

Phytotherapy Research

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High levels of consumption of saturated lipids have been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance (IR).Scutellarin (Scu) is one of the effective traditional Chinese medicines considered beneficial for liver diseases and diabetes. In this study, we investigated the effect of Scu on IR and lipid metabolism disorders in vitro and in high fat diet (HFD)-fed mice. In vitro, we found that Scu decreased insulin-dependent lipid accumulation and the mRNA expression of CD36, Fasn, and ACC in PA-treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation and improved the insulin signalling pathway. Moreover, Scu downregulated mammalian target of rapamycin (mTOR) phosphorylation and the n-SREBP-1c protein level and also reduced lipid accumulation via the mTORdependent pathway, as confirmed by the molecular docking of Scu to mTOR. In HFDfed C57BL/6 mice, Scu improved oral glucose tolerance, pyruvate tolerance and the IR index and also increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR phosphorylation, and decreased the SREBP-1c level in the liver. Taken together, these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte lipid metabolism via the mTOR-dependent pathway through SREBP-1c suppression. K E Y W O R D Shepatic insulin resistance, lipid accumulation, mTOR, n-SREBP-1c

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Section: Resultsmentioning

confidence: 99%

Scutellarin, a modulator of mTOR, attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP‐1c suppression

Luan

Huo

Zhao

et al. 2019

Phytotherapy Research

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“…Most of these parameters were kept at their default values incorporated in the NAMD gui. This simulation approach is based on the conformational sampling of the predominant (especially early-stage) structural changes of the four systems studied here ( Chhatbar et al, 2019 ; Dimić et al, 2020 ). The computational protocol was designed to obtain the basic frameworks for the IL-18 ligand and the ligand bound holo structures.…”

Section: Methodsmentioning

confidence: 99%

Insight into the structures of Interleukin-18 systems

Roy

2020

Computational Biology and Chemistry

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“…Different QSAR methods have been developed and incorporated in various open-source platforms and commercial software ( Table 1). The earliest QSAR-based algorithms include Comparative Molecular Field Analyses (CoMFA) [248] and Comparative Molecular Similarity Indices Analysis (CoMSIA) [249], both of which are still widely used today for various drug discovery endeavors [250][251][252][253]. 3D-QSAR CoMFA was used by Singh and Supuran [252] for the discovery of novel Mtb carbonic anhydrase inhibitors.…”

Section: Similarity-based and Quantitative Structure-activity/propertmentioning

confidence: 99%

In Silico Strategies in Tuberculosis Drug Discovery

et al. 2020

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Tuberculosis (TB) remains a serious threat to global public health, responsible for an estimated 1.5 million mortalities in 2018. While there are available therapeutics for this infection, slow-acting drugs, poor patient compliance, drug toxicity, and drug resistance require the discovery of novel TB drugs. Discovering new and more potent antibiotics that target novel TB protein targets is an attractive strategy towards controlling the global TB epidemic. In silico strategies can be applied at multiple stages of the drug discovery paradigm to expedite the identification of novel anti-TB therapeutics. In this paper, we discuss the current TB treatment, emergence of drug resistance, and the effective application of computational tools to the different stages of TB drug discovery when combined with traditional biochemical methods. We will also highlight the strengths and points of improvement in in silico TB drug discovery research, as well as possible future perspectives in this field.

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CoMFA, CoMSIA, Topomer CoMFA, HQSAR, molecular docking and molecular dynamics simulations study of triazine morpholino derivatives as mTOR inhibitors for the treatment of breast cancer

Cited by 33 publications

References 30 publications

Scutellarin, a modulator of mTOR, attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP‐1c suppression

Scutellarin, a modulator of mTOR, attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP‐1c suppression

Insight into the structures of Interleukin-18 systems

In Silico Strategies in Tuberculosis Drug Discovery

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