Design and synthesis of novel sulphamide tethered quinazolinone hybrids as potential antitumor agents

• Published in: Journal of molecular structure Vol. 1181; pp. 403 - 411
• Main Authors: Venkatesh, Ramineni, Kasaboina, Suresh, Jain, Nishant, Janardhan, Sridhara, Holagunda, Uma Devi, Nagarapu, Lingaiah
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.04.2019
• Subjects: Antitumor activity; Docking studies; Quinazolinones scaffolds; Sulphamides; Docking studies; Antitumor activity; Quinazolinones scaffolds; Sulphamides
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2018.12.098

In an attempt to develop potential and selective antitumor agents, a series of novel sulphamide tethered quinazolinone hybrids were efficiently synthesized and evaluated for antitumor activity against four cancer cell lines such as HeLa (cervical), MDA-MB-231 (breast), PANC-1 (pancreatic), and A549 (lung) in vitro. All the compounds (5a-j, 6a-g) exhibited significant anti-proliferative activity with GI50 values ranging from 0.045 to 6.94 μM, while compound 10c showed potent activity against all the cell lines (He La, MDA-MB-231, PANC-1 and A549) with GI50 values ranging from 0.09 to 0.21 μM. We have explored the binding mode and key active site interactions in HDAC8 and EHMT2 proteins. The docking results are complementary to the experimental results. A series of novel sulphamide tethered quinazolinone derivatives were efficiently synthesized and evaluated for antitumor activity against four cancer cell lines. [Display omitted] •Novel sulphamide tethered quinazolinones hybrids were efficiently synthesized.•Compounds 5a-j, 6a-g screened in viability assays against human cancer cell lines.•5c Showed potent cytotoxicity against four cancers cell lines with GI50 0.09–0.21 μM.•5i, 6f Showed cytotoxic against cancer cell lines with GI50 0.045–0.35 μM.•5c Showed Binding mode and identified key active site residues in HDAC8 and EHMT2 proteins.