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

Sarita Singh; Ateeque Ahmad; Dushyant Singh Raghuvanshi; Mohammad Hasanain; Karishma Agarwal; Vijaya Dubey; Kaniz Fatima; Sarfaraz Alam; Jayanta Sarkar; Suaib Luqman; Feroz Khan; Sudeep Tandon; Atul Gupta

doi:10.1016/j.bmcl.2016.09.036

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. Epub 2016 Sep 15.

Authors

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: atisky2001@yahoo.co.in.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Benzopyrans / chemical synthesis*
Benzopyrans / pharmacology*
Cell Line, Tumor
Humans
Inhibitory Concentration 50
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzopyrans
benzopyran-4-one