Affiliations 

  • 1 1Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001 India
  • 2 2Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor Darul Ehsan Malaysia
  • 3 5Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452 Kingdom of Saudi Arabia
BMC Chem, 2019 Dec;13(1):96.
PMID: 31355369 DOI: 10.1186/s13065-019-0613-8

Abstract

Heterocyclic 1,3-diazine nucleus is a valuable pharmacophore in the field of medicinal chemistry and exhibit a wide spectrum of biological activities. PharmMapper, a robust online tool used for establishing the target proteins based on reverse pharmacophore mapping. PharmMapper study is carried out to explore the pharmacological activity of 1,3-diazine derivatives using reverse docking program. PharmMapper, an open web server was used to recognize for all the feasible target proteins for the developed compounds through reverse pharmacophore mapping. The results were analyzed via molecular docking with maestro v11.5 (Schrodinger 2018-1) using GTPase HRas as possible target. The molecular docking studies displayed the binding behavior of 1,3-diazine within GTP binding pocket. From the docking study compounds s3 and s14 showed better docked score with anticancer potency against cancer cell line (HCT116). Hence, the GTPase HRas may be the possible target of 1,3-diazine derivatives for their anticancer activity where the retrieved information may be quite useful for developing rational drug designing. Furthermore the selected 1,3-diazine compounds were evaluated for their in vitro anticancer activity against murine macrophages cell line. 1,3-Diazine compounds exhibited good selectivity of the compounds towards the human colorectal carcinoma cell line instead of the murine macrophages. The toxicity study of the most active compounds was also performed on non cancerous HEK-293 cell line.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.