Reverse docking study unravels the potential Mycobacterium tuberculosis enzyme targets of Agelasine F

Billones, Junie B.

doi:10.13005/ojc/320210

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…[70][71][72][73][74][75][76] Reverse or inverse molecular docking helps in determining the probable protein targets of a ligand and shed some light on the possible mechanism of action of a drug. 47,48 In this study, reverse docking was conducted to investigate the interaction between syringin and various angiogenesis-related proteins at the molecular level, particularly examining the hydrogen bonds, van der Waals and hydrophobic interactions, which are the principal driving force in maintaining a stable ligand-protein complex. 77…”

Section: Reverse Molecular Docking Analysismentioning

confidence: 99%

“…In this work, reverse molecular docking technique 47 , 48 was conducted to understand the interaction of syringin with the molecular mediators involved in the multifaceted interplay in angiogenesis. The anti-angiogenic activity of syringin was evaluated through the chorioallantoic membrane (CAM) assay and the probable molecular targets of the title compound were identified using the reverse docking technique.…”

Section: Introductionmentioning

confidence: 99%

“…These include Gefitinib, 40 Erlotinib, 41 Sorafenib, 42 Lapatinib, 43 Abiraterone, 44 and Crizotinib, 45 which are all approved medications that are initially discovered using computational methods. 46 In this work, reverse molecular docking technique 47,48 was conducted to understand the interaction of syringin with the molecular mediators involved in the multifaceted interplay in angiogenesis. The anti-angiogenic activity of syringin was evaluated through the chorioallantoic membrane (CAM) assay and the probable molecular targets of the title compound were identified using the reverse docking technique.…”

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confidence: 99%

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In Ovo and In Silico Evaluation of the Anti-Angiogenic Potential of Syringin

Aventurado¹,

Billones²,

Vasquez³

et al. 2020

DDDT

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Introduction: Cancer is considered as one of the deadliest human diseases today. Angiogenesis, the propagation of new blood vessels from pre-existing vasculature, is a critical step in the progression of cancer as it is essential in the growth and metastasis of tumors. Hence, suppression of angiogenesis is a promising approach in cancer therapy. Syringin, a phenylpropanoid glycoside with a molecular formula of C 17 H 24 O 9 , has been found to exhibit chemopreventive effects. However, its anti-angiogenic activity and the underlying mechanism of action are still unknown. Methods: In this work, in ovo chorioallantoic membrane (CAM) assay has been conducted to evaluate the effect of syringin on neovascularization. Additionally, reverse molecular docking studies have been performed in order to identify the probable enzyme targets in the angiogenesis pathway. Results: Treatment with syringin showed significant dose-dependent inhibition of blood vessel length and junctions in the CAM of duck eggs; the anti-angiogenic activity of syringin at 100 µM and 200 µM is comparable with 200 µM of the positive control celecoxib. The results of reverse docking studies indicate that syringin binds the strongest to dihydrofolate reductase (DHFR) and, to some extent, with transforming growth factorbeta receptor type 1 (TGF-βR1), vascular endothelial growth factor receptor 2 (VEGFR2), and matrix metalloproteinase-2 (MMP-2). Furthermore, ADMET models revealed that syringin potentially possesses excellent pharmacokinetic and toxicity profiles. Conclusion: This study demonstrates the potential of syringin as an anti-angiogenic agent and elicits further investigations to establish its application in cancer suppression.

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Section: Reverse Molecular Docking Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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In Ovo and In Silico Evaluation of the Anti-Angiogenic Potential of Syringin

Aventurado¹,

Billones²,

Vasquez³

et al. 2020

DDDT

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“…[1e], Agelasine F is found to display cytotoxicity against a variety of cancer cell lines[1e], [3d] and microorganisms[1e], [2a], including profound activity against Mycobacterium tuberculosis . [3b] A reverse docking study has revealed mycobacterial enoyl reductase and 7,8‐diaminopelargonic acid synthase as a possible enzyme target, but generally the mechanism(s) of action for agelasines are poorly understood. Racemic agelasine F ( 6 ) was synthesized ca.…”

Section: Introductionmentioning

confidence: 99%

The First Synthesis of (–)‐Agelasine F; an Antimycobacterial Natural Product Found in Marine Sponges in the Agelas Genus

Paulsen

Gundersen

2020

Eur J Org Chem

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Agelasine F (also known as ageline A) is a diterpene-adenine hybrid natural product isolated from marine sponges (Agelas species) and this compound is known to display cytotoxic activity against a variety of cancer cell lines as well as microorganisms. We herein report the first total synthesis of (-)-agelasine F. The commercially available and inexpensive monoterpenoid (S)-carvone was found to be a highly suitable starting material for the construction of the terpenoid part [a]

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“…We have applied CADDD approaches in discovering possible leads against druggable targets in Mtb . 8 – 17 An interesting drug target in Mtb is the enzyme 7,8-diaminopelargonic acid (DAPA) aminotransferase, more commonly known as Mtb BioA. BioA is involved in biotin biosynthesis pathway, one of the most important survival pathways of Mtb .…”

Section: Introductionmentioning

confidence: 99%

In silico discovery and in vitro activity of inhibitors against Mycobacterium tuberculosis 7,8-diaminopelargonic acid synthase (Mtb BioA)

Billones

Carrillo

Organo

et al. 2017

DDDT

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Computer-aided drug discovery and development approaches such as virtual screening, molecular docking, and in silico drug property calculations have been utilized in this effort to discover new lead compounds against tuberculosis. The enzyme 7,8-diaminopelargonic acid aminotransferase (BioA) in Mycobacterium tuberculosis (Mtb), primarily involved in the lipid biosynthesis pathway, was chosen as the drug target due to the fact that humans are not capable of synthesizing biotin endogenously. The computational screening of 4.5 million compounds from the Enamine REAL database has ultimately yielded 45 high-scoring, high-affinity compounds with desirable in silico absorption, distribution, metabolism, excretion, and toxicity properties. Seventeen of the 45 compounds were subjected to bioactivity validation using the resazurin microtiter assay. Among the 4 actives, compound 7 ((Z)-N-(2-isopropoxyphenyl)-2-oxo-2-((3-(trifluoromethyl)cyclohexyl)amino)acetimidic acid) displayed inhibitory activity up to 83% at 10 μg/mL concentration against the growth of the Mtb H37Ra strain.

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Reverse docking study unravels the potential Mycobacterium tuberculosis enzyme targets of Agelasine F

Cited by 8 publications

References 26 publications

<p>In Ovo and In Silico Evaluation of the Anti-Angiogenic Potential of Syringin</p>

<p>In Ovo and In Silico Evaluation of the Anti-Angiogenic Potential of Syringin</p>

The First Synthesis of (–)‐Agelasine F; an Antimycobacterial Natural Product Found in Marine Sponges in the Agelas Genus

In silico discovery and in vitro activity of inhibitors against <em>Mycobacterium tuberculosis</em> 7,8-diaminopelargonic acid synthase (<em>Mtb</em> BioA)

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