Synthesis of 3,5-dihydroxy-7,8-dimethoxy-2-(4-methoxyphenyl)benzopyran-4-one derivatives as anticancer agents

  • Bioorg Med Chem Lett. 2016 Nov 1;26(21):5322-5327. doi: 10.1016/j.bmcl.2016.09.036.
Sarita Singh  1 ,  Ateeque Ahmad  2 ,  Dushyant Singh Raghuvanshi  1 ,  Mohammad Hasanain  3 ,  Karishma Agarwal  2 ,  Vijaya Dubey  4 ,  Kaniz Fatima  4 ,  Sarfaraz Alam  5 ,  Jayanta Sarkar  3 ,  Suaib Luqman  4 ,  Feroz Khan  5 ,  Sudeep Tandon  2 ,  Atul Gupta  6
Affiliations
  • 1. Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Kukrail Road, Lucknow 226015, India.
  • 2. Process Chemistry and Technology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Kukrail Road, Lucknow 226015, India.
  • 3. Division of Biochemistry, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226 031, India.
  • 4. Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Kukrail Road, Lucknow 226015, India.
  • 5. Metabolic Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Kukrail Road, Lucknow 226015, India.
  • 6. Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Kukrail Road, Lucknow 226015, India. Electronic address: [email protected].
PMID: 27671497 DOI: 10.1016/j.bmcl.2016.09.036
Abstract

Different alkyl amide (15a-l) and alkyl amine (16a-e) derivatives of 7,8-dimethoxy-3-hydroxy-2-(4-methoxyphenyl)benzopyran-4-one were synthesized and evaluated for their Anticancer activity against five different Cancer cell lines using SRB assay. Compounds 15e, 15i, 15j and 16a-e showed significant Anticancer activity within the range of IC50 2.58-34.86μM. The most promising molecule, 16c, was further analyzed for its effect on cell cycle and Apoptosis of Estrogen receptor positive Cancer cells (MCF-7 cells) which showed that 16c triggered Apoptosis in MCF-7 cells and arrested cells population at sub-G0 (apoptotic) and G2M phase. In tubulin polymerization assay, 16c interfered with kinetics of tubulin polymerization.

Keywords
Anticancer; Benzopyran; Chromanone; Flavone; Flavonoids.