2. Academic Validation
  3. Novel molecular discovery of promising amidine-based thiazole analogues as potent dual Matrix Metalloproteinase-2 and 9 inhibitors: Anticancer activity data with prominent cell cycle arrest and DNA fragmentation analysis effects

Novel molecular discovery of promising amidine-based thiazole analogues as potent dual Matrix Metalloproteinase-2 and 9 inhibitors: Anticancer activity data with prominent cell cycle arrest and DNA fragmentation analysis effects

  • Bioorg Chem. 2020 Aug;101:103992. doi: 10.1016/j.bioorg.2020.103992.
Abdelsattar M Omar 1,  Jürgen Bajorath 2,  Saleh Ihmaid 3,  Hany M Mohamed 4,  Ahmed M El-Agrody 5,  Ahmed Mora 5,  Moustafa E El-Araby 6,  Hany E A Ahmed 7
Affiliations

Affiliations

  • 1 Pharmaceutical Chemistry Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt. Electronic address: asmansour@kau.edu.sa.
  • 2 Department of Life Science Informatics, Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn Endenicher Allee 19c, D-53115 Bonn, Germany.
  • 3 Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia. Electronic address: saleh_ihmaid@yahoo.com.au.
  • 4 Chemistry Department, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia; Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt.
  • 5 Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt.
  • 6 Pharmaceutical Chemistry Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • 7 Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt.
PMID: 32554279 DOI: 10.1016/j.bioorg.2020.103992
Abstract

Thiazole derivatives are known to possess various biological activities such as antiparasitic, Antifungal, antimicrobial and antiproliferative activities. Matrix Metalloproteinases (MMPs) are important Protease target involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have also been reported as potential diagnostic and prognostic biomarkers in many types of Cancer. Herein, new aryl thiazoles were synthesized and evaluated for their Anticancer effects on a panel of Cancer cell lines including the invasive MDA-MB-231 line. Some of these compounds showed IC50 values in the submicromolar range in anti-proliferative assays. In order to examine the relationship between their Anticancer activity and MMPs targets, the compounds were evaluated for their inhibitory effects on MMP-2 and 9. That data obtained revealed that most of these compounds were potent dual MMP-2/9 inhibitors at nanomolar concentrations. Among these, 2-(1-(2-(2-((E)-4-iodobenzylidene)hydrazineyl)-4-methylthiazol-5-yl)ethylidene)hydrazine-1-carboximidamide (4a) was the most potent non-selective dual MMP-2/9 inhibitor with inhibitory concentrations of 56 and 38 nM respectively. When compound 4a was tested in an MDA-MB-231, HCT-116, MCF-7 model, it effectively inhibited tumor growth, strongly induced Cancer cell Apoptosis, inhibit cell migration, and suppressed cell cycle progression leading to DNA fragmentation. Taken together, the results of our studies indicate that the newly discovered thiazole-based MMP-2/9 inhibitors have significant potential for Anticancer treatment.

Keywords

2-aminothiazole; Amidine; Anticancer activity; MMP-2/9 inhibition; Structure-based design.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-147867
    MMP-2/9 Inhibitor
    MMP