WS03.4 Angiotensin receptor blockers reverse cystic fibrosis (CF)-related mucociliary dysfunction in vitro and in a novel CF sheep model in vivo

Inhibitory Perspective of New Synthesized Compounds against Angiotensin Receptor: Schrodinger-based Induced-Fit Molecular Docking

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i32a31718 ◽

2021 ◽

pp. 79-87

Author(s):

Sethy Silky ◽

Dhiman Neerupma ◽

Garg Arun

Keyword(s):

In Silico ◽

Angiotensin Receptor Blockers ◽

In Vivo Studies ◽

Angiotensin Receptor ◽

Standard Drug ◽

Lipinski’S Rule ◽

In Silico Study ◽

Receptor Blockers

Angiotensin is a hormone that plays a key role in the development of hypertension. Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) are now the most often prescribed drugs to treat hypertension. The present in silico study involves exploring the antihypertensive potentials of substituted benzimidazoles and indazole compounds ARC 36, ARC 38, ARC 45, ARC 76, and ARC 77 against the most prominent molecular target Angiotensin Receptor (PDB ID: 4YAY, XFEL structure of Human Angiotensin Receptor)using the software Schrodinger Maestro .Based on glide score, ARC 45, ARC 76 and ARC77 were having the docking score of -7.461 Kcal/mol, -7.947 Kcal/mol and -6.683 Kcal/mol which is comparable to the standard drug (Telmisartan) -5.036.The compounds were further screened for Lipinski’s rule for drug-likeliness, and ADME properties. In this study we reported compounds ARC 76 and ARC38had comparable in silico parameters to the standard dug Telmisartan and hence necessitating further in vitro and in vivo studies.

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ANGIOTENSIN RECEPTOR BLOCKERS IMPROVED CARDIOMYOGENIC TRANSDIFFERENTIATION EFFICIENCY OF HUMAN MARROW-DERIVED MESENCHYMAL STEM CELLS IN VITRO

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(10)60184-2 ◽

2010 ◽

Vol 55 (10) ◽

pp. A19.E183

Author(s):

Yohei Numasawa ◽

Shunichiro Miyoshi ◽

Takehiro Kimura ◽

Nobuhiro Nishiyama ◽

Hiroko Tsuji ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Angiotensin Receptor Blockers ◽

Angiotensin Receptor ◽

Receptor Blockers

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Systematic Cell Line-Based Identification of Drugs Modifying ACE2 Expression

10.20944/preprints202003.0446.v1 ◽

2020 ◽

Cited By ~ 4

Author(s):

Sanju Sinha ◽

Kuoyuan Cheng ◽

Kenneth Aldape ◽

Eyal Schiff ◽

Eytan Ruppin

Keyword(s):

Ace Inhibitors ◽

Angiotensin Receptor Blockers ◽

Drug Effects ◽

Cellular Protein ◽

In Vivo Studies ◽

Receptor Blockers ◽

Approved Drugs ◽

Vitamin A Derivative

The COVID-19 pandemic caused by SARS-COV-2 has infected over 500,000 people causing over 25,000 deaths in the last 10 weeks. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2). Recent studies have reported that patients with hypertension and diabetes treated with ACE inhibitors or angiotensin receptor blockers might be at a higher risk of COVID-19 infection as these drugs have been reported to increase ACE2 expression. This has raised the need to systematically investigate the effect of different drugs including antihypertensives on modulating ACE2 expression. Here, we analyzed a publicly available CMAP dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules. We show that only one subclass of antihypertensives drugs - ACE inhibitors, are significantly enriched for drugs up-regulating ACE2 expression. Studying the effects of the 672 clinically approved drugs in CMAP, we chart the drug categories that affect ACE2 expression. Specifically, we find that panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator. Our results provide initial candidates guiding further in vitro and in vivo studies aimed at assessing drug effects on ACE2 expression.

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Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer’s Mice

Pharmaceuticals ◽

10.3390/ph14020166 ◽

2021 ◽

Vol 14 (2) ◽

pp. 166

Author(s):

Henning Johannes Drews ◽

Roman Klein ◽

Ali Lourhmati ◽

Marine Buadze ◽

Elke Schaeffeler ◽

...

Keyword(s):

Cell Motility ◽

Angiotensin Receptor Blockers ◽

Intraperitoneal Administration ◽

Beneficial Effects ◽

Receptor Blockers ◽

Delivery Route ◽

Interstudy Variability ◽

New Strategies

Angiotensin receptor blockers (ARBs) have demonstrated multiple neuroprotective benefits in Alzheimer’s disease (AD) models. However, their beneficial effects on memory deficits, cholinergic activity, neurogenesis and Amyloid beta (Aβ) clearance reveal significant interstudy variability. The delivery route can impact not only delivery but also targeting and therapeutic efficacy of ARBs. Our previous findings on the beneficial effects of intranasally delivered losartan in the APP/PS1 model of AD prompted us to explore the influence of the delivery route by employing here the systemic administration of losartan. Consistent with our previous results with intranasal losartan, repeated intraperitoneal administration (10 mg/kg) resulted in a remarkable decrease in Aβ plaques and soluble Aβ42, as well as inflammatory cytokines (IL-2, IL-6 and TNFα). The Aβ reduction can be ascribed to its facilitated degradation by neprilysin and diminished generation by BACE1. Losartan increased neurogenesis in vivo and in vitro and improved migratory properties of astrocytes isolated from adult transgenic AD mice. In summary, this data together with our previous results suggest therapeutic features of losartan which are independent of delivery route. The improvement of cell motility of Aβ-affected astrocytes by losartan deserves further in vivo investigation, which may lead to new strategies for AD treatment.

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