Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Synthesis and Antitumor Activity Evaluation of Novel Pyrimidoquinoline Derivatives Publisher



Eghtedari M1 ; Azimzadeh Arani M2 ; Sarrafi Y1 ; Shafiei M2 ; Alimohammadi K3 ; Safari F4 ; Foroumadi A2, 5
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran
  2. 2. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Chemistry, Dr. Shariati Branch, University of Farhangian, Sari, Iran
  4. 4. Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
  5. 5. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

Source: Polycyclic Aromatic Compounds Published:2022


Abstract

Quinoline-based structures possess various types of biological activities and recently have attracted attention as an antitumor scaffold via different known anti-cancer mechanisms. In this study, a novel series of tetrahydropyrimido[4,5-b]quinoline-4,6(3H,7H)-diones (7a-r) were synthesized and evaluated for their in vitro cytotoxic effects on breast cancer cells (MCF-7 cells), prostate cancer cells (LNCaP cells), and normal human adult dermal fibroblast (HDF) cells. Among them, the compounds (7c), (7d), (7 g), (7j), (7k), (7 l), and (7r) showed high activity against LNCaP and MCF-7 cancer cells with IC50 values ranging from 37.62 to 67.3 µM, compared to etoposide as reference drug. The compound (7 l) was the most active compound against LNCaP cancer cells and was examined for further 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining which confirmed apoptosis and DNA damage in LNCaP cells. The study showed upregulation of Bax and downregulation of Bcl-2 as two potential markers of an intrinsic pathway of apoptosis in LNCaP cell line by using quantitative real-time PCR (qRT-PCR) method. Finally, we found that compound 7I can be considered as a potential agent for induction of apoptosis in cancer cells (LNCaP cells). (Figure presented.). © 2021 Taylor & Francis Group, LLC.