In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5

Arya, Hemant; Syed, Safiulla Basha; Singh, Shivom; Ampasala, Dinakar R.; Coumar, Mohane Selvaraj

doi:10.1007/s12539-017-0243-6

Cited by 25 publications

(11 citation statements)

References 48 publications

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“…For instance, Ahmad et al [68] used molecular docking to study the potential ACE inhibitory activities and interaction conformations of nine polyphenolic compounds from Peperomia pellucida (L) Kunth. In other work, Arya et al [69] studied the mode of action of chemical constituents of Clerodendrum colebrookianum against the anti-hypertensive drug targets Rho-associated coiled-coil protein kinase (ROCK), ACE, and phosphodiesterase 5 (PDE5) by using docking and MD simulations. They reported the mode of action of acteoside and osmanthuside β6 as ACE inhibitors.…”

Section: -Bis(dihydrocaffeoyl)-spermidine)mentioning

confidence: 99%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

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The angiotensin-converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase, which has a direct involvement in the control of blood pressure by performing the hydrolysis of angiotensin I to produce angiotensin II. At the same time, ACE hydrolyzes other substrates such as the vasodilator peptide bradykinin and the anti-inflammatory peptide N-acetyl-SDKP. In this sense, ACE inhibitors are bioactive substances with potential use as medicinal products for treatment or prevention of hypertension, heart failures, myocardial infarction, and other important diseases. This review examined the most recent literature reporting ACE inhibitors with the help of molecular modeling. The examples exposed here demonstrate that molecular modeling methods, including docking, molecular dynamics (MD) simulations, quantitative structure-activity relationship (QSAR), etc, are essential for a complete structural picture of the mode of action of ACE inhibitors, where molecular docking has a key role. Examples show that too many works identified ACE inhibitory activities of natural peptides and peptides obtained from hydrolysates. In addition, other works report non-peptide compounds extracted from natural sources and synthetic compounds. In all these cases, molecular docking was used to provide explanation of the chemical interactions between inhibitors and the ACE binding sites. For docking applications, most of the examples exposed here do not consider that: (i) ACE has two domains (nACE and cACE) with available X-ray structures, which are relevant for the design of selective inhibitors, and (ii) nACE and cACE binding sites have large dimensions, which leads to non-reliable solutions during docking calculations. In support of the solution of these problems, the structural information found in Protein Data Bank (PDB) was used to perform an interaction fingerprints (IFPs) analysis applied on both nACE and cACE domains. This analysis provides plots that identify the chemical interactions between ligands and both ACE binding sites, which can be used to guide docking experiments in the search of selective natural components or novel drugs. In addition, the use of hydrogen bond constraints in the S2 and S2′ subsites of nACE and cACE are suggested to guarantee that docking solutions are reliable.

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Section: -Bis(dihydrocaffeoyl)-spermidine)mentioning

confidence: 99%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

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“…Antihypertensive activity 100 µg/mL of aqueous extract (AECc), its aqueous, n-butanol (nBFCc), Ethyl-acetate (EtFCc) and Chloroform fractions of Clerodendrum colebrookianum leaves showed calcium antagonism in rat ileum and at 50 µg/mL and 75 µg/mL doses exhibited Rho-associated coiled-coil protein kinase (ROCK-II), phosphodiesterase-5 (PDE-5) inhibition respectively where, EtFCc was caused maximum 68.62% (ROCK-II) and 52.28% (PDE-5) inhibition, but none of the test sample was exhibit effect in angiotension converting enzyme (ACE) at 100 µg/mL. The test samples also showed negative inotropic and chronotropic effect on isolated frog heart and significant (P<0.001) reduction in systolic blood pressure and heart rate in hypertensive rats compared to control 24 . Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the Clerodendrum colebrookianum to interact with the anti-hypertensive drug targets with good glide score.…”

Section: Antimicrobial Activitymentioning

confidence: 92%

Phytochemical and Pharmacological Properties of Clerodendrum Colebrookianum Walp: A Review

Lalrinpuia¹,

Bora²,

Upadhyay³

et al. 2018

Int. J. Res. Ayurveda Pharm.

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Clerodendrum colebrookianum Walp is a perennial shrub which is native to South and Southeast Asia. Traditionally, it is used in the treatment of various diseases due to its immense therapeutic potential. It is widely used by the indigenous people of Northeast India as a remedy for treatment of various diseases like diabetes, hypertension, stomachache, jaundice, cough and rheumatism. The plant possesses different biologically active components like Colebrin A, Colebrin B, Colebrin D, Colebrin E, β-Sitosterol etc. This review reported various pharmacological activities of the plant such as antihypertensive, anti-inflammatory, analgesic, hepatoprotective, antioxidant, anthelmintic and some other activities which provide scientific evidence for some traditional therapeutic claims.

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“…Te bioactive natural compounds (NCs) of Clerodendrum sp. were retrieved through extensive literature survey [20][21][22][23]. Te two dimensional (2D) structures of the compounds were retrieved from PubChem and Chemspider databases and prepared into a library.…”

Section: Collection Of Natural Compounds and Space Analysismentioning

confidence: 99%

Virtual Screening and Network Pharmacology-Based Study to Explore the Pharmacological Mechanism of Clerodendrum Species for Anticancer Treatment

Gogoi

Saikia

2022

Evidence-Based Complementary and Alternative Medicine

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Background. Cancer is a second leading cause of death in the world, killing approximately 3500 per million people each year. Therefore, the drugs with multitarget pharmacology based on biological networks are crucial to investigate the molecular mechanisms of cancer drugs and repurpose the existing drugs to reduce adverse effects. Clerodendrum is a diversified genus with a wide range of economic and pharmacological properties. Limited studies were conducted on the genus’s putative anticancer properties and the mechanisms of action based on biological networks remains unknown. This study was aimed to construct the possible compound/target/pathway biological networks for anticancer effect of Clerodendrum sp. using docking weighted network pharmacological approach and to investigate its potential mechanism of action. Methods. A total of 194 natural Clerodendrum sp. Compounds were retrieved from public databases and screened using eight molecular descriptors. The cancer-associated gene targets were retrieved from databases and the function of the target genes with related pathways were examined. Cytoscape v3.7.2 was used to build three major networks: compound-target network, target-target pathway network, and compound-target-pathway network. Results. Our finding indicates that the anticancer activity of Clerodendrum sp. involves 6 compounds, 9 targets, and 63 signaling pathways, resulting in multicompounds, multitargets, and multipathways networks. Additionally, molecular dynamics (MD) simulations were used to estimate the binding affinity of the best hit protein-ligand complexes. Conclusion. This study suggests the potential anticancer activity of Clerodendrum sp. which could further contribute to scavenger novel compounds for the development of new alternative anticancer drugs.

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In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5

Cited by 25 publications

References 48 publications

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Phytochemical and Pharmacological Properties of Clerodendrum Colebrookianum Walp: A Review

Virtual Screening and Network Pharmacology-Based Study to Explore the Pharmacological Mechanism of Clerodendrum Species for Anticancer Treatment

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