Synthesis, estrogen receptor binding affinity and molecular docking of pyrimidine-piperazine-chromene and -quinoline conjugates. Issue 18 (15th September 2017)

• Record Type: Journal Article
• Authors: Parveen, Iram; Ahmed, Naseem; Idrees, Danish; Khan, Parvez; Hassan, Md. Imtaiyaz
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 18(2017)
• Page Start: 4493
• Page End: 4499
• Publication Date: 2017-09-15
• Subjects: Chromene conjugates -- Quinoline conjugates -- Anti-proliferative activity -- Molecular docking -- SAR study; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.07.077
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Multi-component reaction under mild reaction condition. Tolerance of functional groups. Good anti-proliferative activity of products against MCF-7 cells. Good binding affinity of products with Bcl-2 protein. Abstract: Substituted 2-amino-7-((6-(4-(2-hydroxyethyl) piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-4H-chromene-3-carbonitriles and 2-amino-7-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-1, 4-dihydroquinoline-3-carbonitriles were synthesized via an efficient multi-component one pot synthesis under mild conditions. These compounds1 –20 were evaluated against human breast cancer cell lines (MCF-7) and human embryonic kidney cells (HEK293) for cytotoxic activities. Among them, compounds6, 7, 15, 17 and19 showed better anti-proliferative activities as (IC50 value48 ± 1.70, 65 ± 1.13, 92 ± 1.18, 30 ± 1.17 and16 ± 1.10 µM) than curcumin drug (48 ± 1.11 µM). Molecular docking was also performed with active compounds6, 7 and15 against Bcl-2 protein which gave good binding affinity (ΔG = −9.08, −8.29 and−7.70 kcal/mol) respectively. Furthermore, the structure-activity relationship (SAR) analysis revealed that the chromene and quinoline moieties, when attached with pyrimide and piperazine moieties, enhanced anti-proliferative activities.