Fluorescence-Based Binding Assay for Screening Ligands of Angiotensin Receptors

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

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Impact of Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptors Blockers on Mortality in Acute Heart Failure Patients with Left Ventricular Systolic Dysfunction in the Middle East: Observations from the Gulf Acute Heart Failure Registry (Gulf CARE)

Current Vascular Pharmacology ◽

10.2174/1570161115666170817164420 ◽

2018 ◽

Vol 16 (6) ◽

pp. 596-602

Author(s):

Ibrahim Al-Zakwani ◽

Kadhim Sulaiman ◽

Jawad A. Al-Lawati ◽

Alawi A. Alsheikh-Ali ◽

Prashanth Panduranga ◽

...

Keyword(s):

Heart Failure ◽

Acute Heart Failure ◽

Enzyme Inhibitors ◽

Left Ventricular Systolic Dysfunction ◽

Systolic Dysfunction ◽

Angiotensin Converting Enzyme Inhibitors ◽

Left Ventricular ◽

Angiotensin Receptors ◽

Ventricular Systolic Dysfunction ◽

Converting Enzyme Inhibitors

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Coumarin-Fatty Acid Conjugates as Potential ERα/AKT-1 Antagonists for ER Positive Breast Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666191028104339 ◽

2020 ◽

Vol 20 (4) ◽

pp. 437-449

Author(s):

Jubie Selvaraj ◽

Jameera B.A. John ◽

Nanjan M. Joghee ◽

Justin Antony ◽

Ashish Wadhwani ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Fatty Acid ◽

Binding Assay ◽

Uterine Cancer ◽

Design Development ◽

Structure Based Drug Design ◽

Ic50 Values ◽

Cancer Activity

Background: : Current drugs used for the treatment of hormone-dependent breast cancer function as anti-estrogens in the breast, in addition to Estrogen Receptor (ER) agonists in the uterus, thus elevate a woman’s risk of developing uterine cancer. This is due to the lack of selective binding and partial agonistic effect of these drugs towards estrogen receptors. In recent years, therefore, researchers have turned their attention towards antiestrogens devoid of these agonist properties and thus have a mechanism of action different from the existing drugs. Objective:: In this context, we report here the design, development and in vitro evaluation of some novel pharmacophores containing coumarin and fatty acid scaffolds for their anti-breast cancer activity. Methods: : A library of coumarin-fatty acid conjugates was designed using structure-based drug design approach. The conjugates which have shown good in silico results were then synthesized, characterized and evaluated for their anti-breast cancer activity by MTT assay, Apoptotic assay, Cell proliferation assay, Estrogen binding assay and Gene expression study. Results: Out of the fifteen compounds screened, two compounds, SAC-2 and LNAC-2, showed good activity with IC50 values 22µg/ml, 25μg/ml, respectively. These compounds suppressed the proliferation of ER overexpressed MCF-7 cells, increased ERα degradation and hence inactivate the ERα pathway. ER binding assay and gene expression RT-PCR study reveal that SAC-2 downregulated the expression of ERα receptor and AKT-1 gene. Conclusion:: Compound SAC-2 is a good antagonist to ER and hence has a potential for treating breast cancer and other cancers where AKT plays an important role.

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