Synthesis and antiproliferative activity of sulfonamide-based peptidomimetic calpain inhibitors.

08:00 EDT 13th March 2020 | BioPortfolio

Summary of "Synthesis and antiproliferative activity of sulfonamide-based peptidomimetic calpain inhibitors."

The calpains are a conserved family of cysteine proteases that includes several isoforms of which µ-calpain and m-calpain are the most widely distributed in mammalian cells. Calpains have been implicated in normal physiological processes as well as cellular abnormalities such as neurodegenerative disorders, cataract, and cancer. Therefore, calpain inhibitors are of interest as potential therapeutic agents. We have synthesized four new sulfonamide-based peptidomimetic compounds 2-5 as inhibitors of μ-calpain that incorporate (E)-1-(phenyl)-2-phenyldiazene and (E)-1-(phenyl)-2-phenylethene functionalities as the N-terminal capping groups of the inhibitors. Compound 5 with K value of 9 nM versus μ-calpain was the most potent member of the group. The compounds were predicted to be more lipophilic compared to MDL28170 based on CLogP estimation. They displayed moderate to good antiproliferative activity versus melanoma cell lines (A-375 and B-16F1) and PC-3 prostate cancer cells in vitro. Additionally, one member of the group (compound 3) inhibited DU-145 cell invasion by 80% at 2 μM concentration in the Matrigel cell invasion assay.


Journal Details

This article was published in the following journal.

Name: Bioorganic & medicinal chemistry
ISSN: 1464-3391
Pages: 115433


DeepDyve research library

PubMed Articles [28991 Associated PubMed Articles listed on BioPortfolio]

Synthesis and SAR studies of novel 1,2,4-oxadiazole-sulfonamide based compounds as potential anticancer agents for colorectal cancer therapy.

A diverse series of 1,2,4-oxadiazoles based substituted compounds were designed, synthesized and evaluated as anticancer agents targeting carbonic anhydrase IX (CAIX). Initial structure-activity analy...

Sulfonamide-based ring-fused analogues for CAN508 as novel carbonic anhydrase inhibitors endowed with antitumor activity: Design, synthesis, and in vitro biological evaluation.

In the present study, we report the design and synthesis of novel CAN508 sulfonamide-based analogues (4, 8a-e, 9a-h and 10a-e) as novel carbonic anhydrase (CA) inhibitors with potential CDK inhibitory...

Synthesis of coumarin-sulfonamide derivatives and determination of their cytotoxicity, carbonic anhydrase inhibitory and molecular docking studies.

Carbonic anhydrases isoforms CA IX, and XII are known to be highly expressed in various human tissues and malignancies. CA IX is a prominent target for especially colorectal cancers, because it is ove...

In silico design, synthesis and activity of potential drug-like chrysin scaffold-derived selective EGFR inhibitors as anticancer agents.

Epidermal growth factor receptor (EGFR) signaling pathway is one of the promising and well-established targets for anticancer therapy. The objective of the present study was to identify new EGFR inhib...

Verapamil decreases calpain-1 and matrix metalloproteinase-2 activities and improves hypertension-induced hypertrophic cardiac remodeling in rats.

Increased activity of calpain-1 and matrix metalloproteinase (MMP)-2 was observed in different models of arterial hypertension and contribute to thicken the left ventricle (LV) walls and to hypertroph...

Clinical Trials [9360 Associated Clinical Trials listed on BioPortfolio]

Chloroquinoxaline Sulfonamide in Treating Patients With Stage IV Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of chloroquinoxa...

Effect of Diabetes Mellitus on Cholesterol Metabolism

HMG CoA reductase inhibitors (statins) are commonly used to treat high cholesterol (HC) in both type 1 and type 2 diabetes mellitus (DM). Several studies have shown benefits of statin amon...

A Phase II Trial of All-Trans-Retinoic Acid in Combination With Interferon-Alpha 2a in Children With Recurrent Neuroblastoma or Wilms' Tumor

A body of preclinical data has provided a strong rationale for evaluating the combination of IFN-alpha with retinoic acid. The two drugs have different mechanisms of action and, when used...

Pharmacological Intervention in Diabetic Retinopathy

The purpose of this study is to determine if diabetic retinopathy can be treated with prostaglandin analogues, prostaglandin synthesis inhibitors or carbonic anhydrases inhibitors.

Irinotecan/Cisplatin Plus Simvastatin in Extensive Disease-Small Cell Lung Cancer (ED-SCLC)

3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly referred to as the statins, have proven therapeutic and preventative effects in cardiovascular diseases. Recently, there are e...

Medical and Biotech [MESH] Definitions

One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity.

An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.

Compounds that bind to and inhibit enzymes involved in the synthesis of STEROIDS.

N-Glycosidases that remove adenines from RIBOSOMAL RNA, depurinating the conserved alpha-sarcin loop of 28S RIBOSOMAL RNA. They often consist of a toxic A subunit and a binding lectin B subunit. They may be considered as PROTEIN SYNTHESIS INHIBITORS. They are found in many PLANTS and have cytotoxic and antiviral activity.

A short-acting sulfonamide antibacterial with activity against a wide range of gram- negative and gram-positive organisms.

Quick Search

DeepDyve research library

Relevant Topics

  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Skin cancers
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Basal cell carcinoma Basal cell carcinoma, or BCC, is a cancer of the basal cells at the bottom of the epidermis. It’s very common ...

Searches Linking to this Article